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Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 x 10(-s)) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets., National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [R01 AR070148]; National Institute of Arthritis and Musculoskeletal and Skin DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [U54 AR057319, U01 AR51874 04]; National Center for Research ResourcesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [U54 RR019497]; Office of Rare Diseases Research of the National Center for Advancing Translational Sciences; Imperial College, National Institute for Health Research, Biomedical Research Centre; Wellcome TrustWellcome TrustEuropean Commission [WT107881]; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [MC_UU_00002/4], This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health grant R01 AR070148 to A.H.S. The Vasculitis Clinical Research Consortium has received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54 AR057319 and U01 AR51874 04), the National Center for Research Resources (U54 RR019497), and the Office of Rare Diseases Research of the National Center for Advancing Translational Sciences. J.C.M., A.P.K., and R.M.M. acknowledge support from the Imperial College, National Institute for Health Research, Biomedical Research Centre. C.W. and G.R. acknowledge support from The Wellcome Trust (WT107881) and the Medical Research Council (MC_UU_00002/4). This work was supported by the use of study data downloaded from the dbGaP website, under dbGaP: phs000272.v1.p1, phs000431.v2.p1, phs000583.v1.p1, and phs000444.v1.p1.

BACKGROUND Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder that results in a predisposition to the growth of multiple tumors in the central nervous system, the peripheral nervous system, and the skin. The clinical manifestations of neurofibromatosis are associated with loss of neurofibromin expression which causes the upregulation of the RAS pathway. Although neurofibromatosis type 1 can be diagnosed based on the National Institutes of Health criteria, sometimes the diagnosis is difficult, in cases where the characteristic features do not develop. Moreover, other RAS-related disorders may present with significantly overlapping clinical features. AIMS To determine the clinical and molecular genetic characteristics of Turkish patients with neurofibromatosis type 1. STUDY DESIGN Cross-sectional study. METHODS For the genetic analysis of 27 Turkish families clinically diagnosed with NF1 between 1990 and 2019, we used a multi-step process consisting of next-generation sequencing, multiplex ligation-dependent probe amplification, and array-comparative genomic hybridization. RESULTS In this study, we identified 11 novel and 11 previously reported single-nucleotide variants in 22 families. Whole gene deletions were detected by multiplex ligation-dependent probe amplification analysis in 3 families. Of those, array comparative genomic hybridization analysis defined a 17q11.2 deletion in 4 patients from 2 families and 1.2-Mb involving 1 unrelated patient. All patients with a deletion had facial dysmorphism, suggesting a peculiar phenotype in this group. We could not find any pathogenic variant in the 2 families that met the National Institutes of Health criteria. CONCLUSION The novel pathogenic variants identified in this study broaden the spectrum of pathogenic variants in NF1 and provide better clinical characterization of NF1. RNA-seq experiments are recommended in patients who meet the National Institutes of Health diagnostic criteria for NF but have not identified any variants in nextgeneration sequencing, multiplex ligation-dependent probe amplification, or array-comparative genomic hybridization analysis.

Objective Behcet's disease is a complex systemic inflammatory vasculitis of incompletely understood etiology. This study was undertaken to investigate genetic associations with Behcet's disease in a diverse multiethnic population. Methods A total of 9,444 patients and controls from 7 different populations were included in this study. Genotyping was performed using an Infinium ImmunoArray-24 v.1.0 or v.2.0 BeadChip. Analysis of expression data from stimulated monocytes, and epigenetic and chromatin interaction analyses were performed. Results We identified 2 novel genetic susceptibility loci for Behcet's disease, including a risk locus in IFNGR1 (rs4896243) (odds ratio [OR] 1.25; P = 2.42 x 10(-9)) and within the intergenic region LNCAROD/DKK1 (rs1660760) (OR 0.78; P = 2.75 x 10(-8)). The risk variants in IFNGR1 significantly increased IFNGR1 messenger RNA expression in lipopolysaccharide-stimulated monocytes. In addition, our results replicated the association (P < 5 x 10(-8)) of 6 previously identified susceptibility loci in Behcet's disease: IL10, IL23R, IL12A-AS1, CCR3, ADO, and LACC1, reinforcing the notion that these loci are strong genetic factors in Behcet's disease shared across ancestries. We also identified >30 genetic susceptibility loci with a suggestive level of association (P < 5 x 10(-5)), which will require replication. Finally, functional annotation of genetic susceptibility loci in Behcet's disease revealed their possible regulatory roles and suggested potential causal genes and molecular mechanisms that could be further investigated. Conclusion We performed the largest genetic association study in Behcet's disease to date. Our findings reveal novel putative functional variants associated with the disease and replicate and extend the genetic associations in other loci across multiple ancestries., National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) [R01AR070148]; NIH [U54GM104938, U19AI082714, UM1AI144292, P30AR053483, P30AR073750], Supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) grant number R01AR070148 to Dr. Sawalha. Recruitment and genotyping of the EuropeanAmerican controls was supported by NIH grants number U54GM104938, U19AI082714, UM1AI144292, P30AR053483, and P30AR073750 to Drs. Guthridge and James. This work was supported by the use of study data downloaded from the dbGaP web site, under dbGaP accession phs000272. v1.p1.

Takayasu arteritis (TA) is a large-cell vasculitis, and is not usually associated with avascular necrosis (AVN). The objective of the study was to investigate any association between TA and AVN, including the possible pathogenic effect of glucocorticoid (GCs) use. The study design was retrospective and cross sectional. TA patients were enrolled in the study. Demographic variables, disease activity, treatments, physician global assessment, Indian Takayasu Clinical activity score 2010, and Kerr criteria were recorded. Logistic regression analysis was performed to identify predictors of AVN. A total of 29 patients were assessed. AVN was observed in four (13.8%) patients with TA. Male gender and elevated C-reactive protein (CRP) were found to be significantly associated with AVN (p = 0.001 and p = 0.006, respectively). While type IIb TA was more common in patients with AVN (n = 2, 50%), type V was more likely in the absence of AVN (n = 13, 52%). Descending aorta and thoracic aorta were usually involved in patients with AVN (both, n = 3, 75%). In multivariate logistic regression, increased CRP levels were the only predictor for AVN (OR = 1.183, 95% Cl = 1.025-1.364, p = 0.021). No association was identified between AVN in TA patients and either duration or cumulative dose of GCs. The present study found that higher CRP levels and male gender were associated with AVN in patients with TA.

Loss or decrease of function in runt-related transcription factor 2 encoded by RUNX2 is known to cause a rare autosomal-dominant skeletal disorder, cleidocranial dysplasia (CCD). Clinical spectrum and genetic findings in 51 CCD patients from 30 unrelated families are herein presented. In a majority of the patients, facial abnormalities, such as delayed fontanel closure (89%), parietal and frontal bossing (80%), metopic groove (77%), midface hypoplasia (94%), and abnormal mobility of shoulders (90%), were recorded following clinical examination. In approximately one-half of the subjects, wormian bone (51%), short stature (43%), bell-shaped thorax (42%), wide pubic symphysis (50%), hypoplastic iliac wing (59%), and chef's hat sign (44%) presented in available radiological examinations. Scoliosis was identified in 28% of the patients. Investigation of RUNX2 revealed small sequence alterations in 90% and gross deletions in 10% of the patients; collectively, 23 variants including 11 novel changes (c.29_30insT, c.203delAinsCG, c.423 + 2delT, c.443_454delTACCAGATGGGAinsG, c.505C > T, c.594_595delCTinsG, c.636_637insC, c.685 + 5G > A, c.1088G > T, c.1281delC, Exon 6-9 deletion) presented high allelic heterogeneity. Novel c.29_30insT is unique in affecting the P1-driven long isoform of RUNX2, which is expected to disrupt the N-terminal region of RUNX2; this was shown in two unrelated phenotypically discordant patients. The clinical findings highlighted mild intra-familial genotype-phenotype correlation in our CCD cohort.

Myeloid/lymphoid neoplasm is a rare malignancy with an aggressive course and rapid transformation to acute myeloid leukemia (AML), or less frequently to acute lymphoblastic leukemia (ALL). Cases with t(8;22)(p11;q11) BCR-FGFR1 fusion gene may be misdiagnosed with chronic myeloid leukemia (CML), due to a very similar morphologic and clinical profile. We report a case of 48-year-old woman who complained of weakness and gastric pain. She had splenomegaly, eosinophilia, and elevated white blood cells. Bone marrow (BM) aspiration biopsy was performed with an initial diagnosis of CML. Cytogenetic analysis of the BM showed a 46,XX,t(8;22)(p11.2;q11.2). She was diagnosed with myeloid/lymphoid neoplasm with eosinophilia and rearrangement of FGFR1 gene. Throughout the chronic phase, the patient was treated with hydroxurea. Additional chromosomal abnormalities developed during therapy. Owing to the (8;22) clone, our patient did not respond to the treatment and rapidly transformed first to B-ALL and then AML. To the best of our knowledge, this is the first MPN patient with rearrangement of BCR and FGFR1 genes with rapid transformation to B-ALL and then to AML. WOS:000606311500003 Q4

Behcet’s disease (BD) and Crohn’s disease (CD) cannot be easily differentiated in young adults presenting with nonspecific gastrointestinal (GI) manifestations due to similar extraintestinal manifestations. We recently showed that increased common femoral vein (CFV) thickness is a distinctive feature of BD, rarely present in other inflammatory or vascular diseases with a specificity higher than 80% for the cutoff value of ≥ 0.5 mm. We suggest that CFV thickness measurement with ultrasonography (US) can be a diagnostic tool for BD. To assess the diagnostic performance of CFV thickness measurement in the differential diagnosis of BD and CD. Patients with BD (n = 69), CD (n = 38), and healthy controls (HC) (n = 38) were included in the study. Bilateral CFV thickness was measured with Doppler US. Both right and left CFV thicknesses were significantly higher in BD compared to HC and CD (for right: 0.76 mm vs 0.33 mm, for left: 0.78 mm vs 0.35 mm, p 0.05 for both). CFV thickness was also similar between BD patients with and without GI involvement (p = 0.367). The diagnostic cutoff values of ≥ 0.5 mm for CFV thickness performed well against to both CD and HCs for discrimination of BD. The sensitivity and specificity rates were > 85% for both HC and CD. Positive and negative predictive values in our tertiary clinical setting were > 90%. We found significantly lower CFV thickness in CD compared to BD. Our results suggest that CFV wall thickness measurement is a distinctive diagnostic tool for the differentiation of BD and CD and can be helpful in daily practice for the differentiation of two diseases.

Chronic lymphocytic leukemia (CLL) is a neoplasm characterized by excessive accumulation of B lymphocytes in the peripheral blood, bone marrow and lymph nodes. We assessed the expressions of 22 genes in the p53 pathway in 30 CLL patients and 15 healthy subjects by a RT2 Profiler PCR (polymerase chain reaction) Array technique and their relation to cytogenetic aberrations detected by fluorescent in situ hybridization (FISH). Our Student’s t-test results indicated that ATM, ATR, BAX, CASP9, CDK4, CDKN2A, CHEK1, CHEK2, E2F3, MCL1, MDM2, MDM4, PCNA, RB1, P53 and BCL2 genes were statistically significant (p (APAF1, CDKN1A, E2F1, GADD45A, PTEN and PTX3) were not statistically significant. The ATM, ATR, BAX, CASP9, CDK4, CDKN1A, CDKN2A, CHEK1, CHEK2, MDM2, MDM4, PCNA, RB1, P53, E2F1, GADD45A and BCL2 genes were found to be upregulated by the 2-ᐃᐃCt (relative fold change in gene expression) method. The highest up-regulation was detected in CDKN2A and BCL2 genes, 10.22- and 8.51-fold, respectively. On the other hand, the PTX3 gene with a fold regulation of 1.84 was found to the highest downregulation. Overall, the CDNK2A BCL2 and PTX3 genes are related to the mechanism of the disease in the p53 pathway and may be an important predictor of the prognosis of the disease. The BCL2 gene may be associated with increased risk of developing CLL. We suggest that the PTX3 gene may be considered as a marker associated with CLL disease. The CDKN2A gene expression seems to play a protective role in CLL.

Objective: Renal tubular acidosis (RTA) is a clinical manifestation that occurs with insufficiency in restoring bicarbonate or disruption in hydrogen ion elimination as a result of a disruption in tubulus functions, causing normal anion gap-opening metabolic acidosis. In the present study, we aimed to investigate the prevalence of RTA in the largest systemic lupus erythematosus (SLE) patient population to date. Materials and Methods: SLE patients, who were followed up in 2 different healthcare centers, were included. Patients with metabolic acidosis (pH 3 Results: A total of 108 patients were included in the present study. The mean age of the patients was 41.5 ± 1.2 and 87% were female. The SLE diagnosis duration was 75 ± 5 months. The mean creatinine value ​​was 0.6 ± 0.1 mg/dL and the mean eGFR was 111 ± 2 mL/min. According to the blood gas analysis, 18 patients (16.7% of the total) had RTA. Sixteen of these patients had type 1 RTA and 2 had type 2 RTA; type 4 RTA was not determined in any of the patients. Conclusion: RTA should be considered in SLE patients even if they have normal eGFR values. This is the largest study to examine the prevalence of RTA in SLE patients in the literature.

Objective: The aim of this multi-center study was to assess predictive factors for work-day loss as an indirect cost element in Behçet's syndrome (BS). Methods: In this cross-sectional, multi-center study, 834 BS patients (F/M: 441/393, age mean: 38.4 ± 10.9 years) were included. Data were collected by a questionnaire regarding treatment protocols, disease duration, smoking pattern, frequency of medical visits during the previous year and self-reported work-day loss during the previous year. Results: Work-day loss was observed in 16.2% of patients (M/F: 103/32). The percentages of being a smoker (81.8%), using immunosuppressive (IS) medications (82%), and having disease duration

Objectives Takayasu's arteritis (TAK) is a rare vasculitis characterized by inflammation of intermediate- to large-size arteries. Although pulmonary artery involvement (PAI) is an expected finding in some TAK patients, data on non-vascular pulmonary involvement (NVPI) are limited. We aimed to investigate the frequency of NVPI, including parenchymal infiltration, nodules/cavities, pleural effusion, and haemorrhage, in TAK. Method We assembled a retrospective cohort of TAK patients from nine tertiary centres in Turkey. The demographics and clinical characteristics of patients were extracted from medical records and the imaging findings were evaluated for pulmonary manifestations. Results As of January 2021, 319 TAK patients (female/male 276/43; mean age 42.4 +/- 13.5 years) were recruited. Eighty-two patients had cough and/or dyspnoea and four had haemoptysis as pulmonary symptoms. On computed tomography assessment, the overall frequency of NVPI was 7.2%; parenchymal infiltrations were present in 10 (3.1%), pleural effusion in eight (2.5%), nodules/cavities in six (1.9%), and pulmonary haemorrhage in four patients (1.3%). In the whole cohort, 10.3% of patients had pulmonary artery hypertension (PAH) and 5.6% had PAI. Among patients with PAH or PAI, the overall frequency of NVPI was significantly higher than in the rest of the group. Conclusions In this TAK cohort from Turkey, we observed NVPI in 7.2% of patients, with parenchymal infiltrations being the most common, followed by pleural effusion. Notably, NVPI was more frequent in patients with PAH or PAI. Although not as common as PAI, NVPI should be kept in mind, especially in TAK patients with PAH or PAI.

To compare the clinical features, laboratory findings, and prognosis of Behçet's disease (BD) patients with and without Budd-Chiari syndrome (BCS).This multicenter retrospective study investigated 61 (M/F: 41/20) patients with BD, having coexistent BCS, and 169 (M/F:100/69) BD patients as the control group without BCS from 22 different centers of Turkey diagnosed between 1990 and 2017.Of the total 61 BD patients with BCS, the onset of the first symptom and the median age of diagnosis were earlier in contrast to BD patients without BCS (p = 0.005 and p = 0.007). Lower extremity deep vein and inferior vena cava (IVC) thrombosis were more common in patients with BCS (all; p 0.01) compared to the control group. Mortality was significantly higher in BD-BCS patients with IVC thrombosis than in the controls (p = 0.004). Since most of the cases in our cohort had chronic and silent form of BCS, mortality rate was 14.8%, which was on the lower range of mortality rate reported in literature (14-47%). While all BD-BCS patients received immunosuppressive (IS) agents, only half of them received additional anticoagulant treatments. Among IS agents, interferon treatment was more frequently used in this cohort (19%), compared to other series reported in literature (2.3%).To our knowledge, this is the largest series of BD patients with BCS. Our patients had earlier disease onset and diagnosis, higher frequency of IVC thrombosis, and higher mortality rate, compared to BD patients without BCS. Mortality was significantly higher in BD-BCS patients with IVC thrombosis compared to controls. Key Points • Mortality rate is higher in BD-associated BCS patients with IVC involvement. • Chronic and silent form of BD-associated BCS has a better prognosis. • The main treatment options are corticosteroids and immunosuppressive agents, whereas anticoagulant treatment remains controversial.

OBJECTIVES The aim of the study is to evaluate the importance of lactate dehydrogenase-to-albumin ratio (LAR) in patients with adult-onset Still's disease (AOSD) and to investigate the relationship between this ratio and clinical laboratory variables. METHODS The study design was retrospective cross-sectional. The demographic and clinical data, laboratory results and imaging findings were documented. Univariate and multinomial logistic regression analyses were performed to find the predictors, which could be useful to define the ferritin level and organ involvement. Receiver-operating characteristic (ROC) analysis was used to clarify the diagnostic ability of the LAR for ferritin level and organ involvement. RESULTS Fifty-eight patients with AOSD were evaluated. When patients were divided into two groups according to the serum ferritin level with a cut-off of 1500 ng/dL, lymphocyte count and albumin level were significantly less in patients who had higher ferritin levels (P = .015 and P = .005). In multinominal logistic regression analysis, AST, LDH and LAR were found as predictors for ferritin levels. When we compared LAR between patients with and without organ involvement, higher LAR was found in patients with HM, SM, serositis and MAS. Also, LAR was significantly higher in patients with higher ferritin levels (≥1500 ng/dL) than those without (P

Objective Although the frequency of metabolic syndrome has been studied separately in psoriasis, psoriatic arthritis (PsA), and rheumatoid arthritis (RA) patients, there is no study that compares the prevalence of metabolic syndrome in all three diseases. The purpose of this study is to evaluate the relationship between metabolic syndrome (MetS) and chronic low-grade inflammatory diseases, and to determine the frequency of MetS and insulin resistance in psoriasis and PsA as compared to RA. Methods A total of 155 patients were included in this cross-sectional study. Fifty patients who were diagnosed with psoriasis, 55 PsA patients who were diagnosed according to the CASPAR criteria, and 50 seropositive RA patients who were diagnosed according to the ACR/EULAR 2010 classification criteria were included in this study. MetS was diagnosed by the 2005 criteria of International Diabetes Federation. The cardiovascular risk factors and parameters associated with MetS were evaluated. Results The patients' mean age was significantly higher in the RA. MetS was determined in 33.5% of all patients and MetS and insulin resistance showed no significant difference among the three groups (psoriasis: 36%, PsA: 29%, RA: 36%; p: 0.684 and psoriasis: 70%, PsA: 64%, RA: 66%, respectively; p: 0.785). Triglyceride levels were higher in psoriasis and PsA as compared to the RA (psoriasis: 34%, PsA: 32.7%, RA: 16%, respectively; p: 0.045). The frequency of hypertension was 38% in the RA, which was higher than PsA and psoriasis (p: 0.011). Conclusion In all three groups, the prevalence of MetS was shown to be higher than the general population. The lack of difference between these groups may be due to the small number of patients, the retrospective study design, and the inequality of the population with respect to age and gender.

OBJECTIVES Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) belongs to the tumor necrosis factor (TNF) superfamily and is reported to play a role in autoimmune diseases. In this study, we aimed to measure serum TRAIL receptor 1 (TRAIL-R1) concentration and assess any phenotypic relationship in patients with ankylosing spondylitis (AS). METHODS Fifty-three patients with AS were recruited from August 2014 to December 2014 cross-sectionally. Fifty-three sex- and age-matched healthy controls were also recruited. Serum TRAIL-R1 concentrations were measured using an enzyme-linked immunosorbent assay. The association between serum TRAIL-R1, TNF-α, disease activity indices, markers of systemic inflammation, and clinical features were evaluated. RESULTS Serum TRAIL-R1 and TNF-α levels were increased in patients with AS compared with healthy controls (4.5 ± 2.3 vs 3.5 ± 2.3 pg/mL, p = 0.036; 3.8 [1.6-7.7] vs 2.0 [0.21-5.7] pg/mL, p = 0.048, respectively). Serum TRAIL-R1 displayed a medium positive correlation with serum TNF-α concentrations (r = 0.412; p = 0.002). Serum TRAIL-R1 concentration was higher in human leucocyte antigen (HLA)-B27-positive patients compared with non-HLA-B27 patients (5.5 ± 2.2 vs 3.1 ± 1.6 pg/mL, p < 0.001). No relationship was found between serum TRAIL-R1 concentration and disease activity scores. CONCLUSIONS This study confirms that serum TRAIL-R1 levels are higher in AS patients than healthy controls. The persistence of significantly elevated serum TRAIL-R1 levels, even in patients with low disease activity or after excluding biologic treatment, and the association with HLA-B27 positivity, warrants further investigation due to the unclear role of TRAIL-R1 in the pathophysiology of AS.

The Scleroderma Health Assessment Questionnaire (SHAQ) is a functional scale which consists of five scleroderma-specific items (overall disease severity, Raynaud’s phenomenon, digital ulcers, respiratory and intestinal involvement) in addition to Health Assessment Questionnaire Disability Index (HAQ-DI). The objective of this study was to perform an adaptation and validation of a Turkish version of the SHAQ. We validated psychometric properties of the scale with 70 consecutive systemic sclerosis (SSc) patients, who fulfilled the 2013 ACR/EULAR classification criteria for SSc. We evaluated test–retest reliability with the intraclass correlation coefficient (ICC), discriminant validity by stratifying patients according to organ involvements and disease subtypes, and convergent validity by testing the correlation between SHAQ and related components of Short Form 36 version 2 (SF-36v2). Internal consistency of the questionnaire was evaluated by Cronbach’s alpha coefficient. The SHAQ-global, visual analogue scales (VAS) of pulmonary, digital ulcer, and Raynaud’s phenomenon were significantly correlated with the physical component score of the SF-36v2 (r = − 0.274, r = − 0.295, r = − 0.326, r = − 0.308, p

Background Multiple myeloma is a plasma cell dyscrasia characterized by transformation of B cells into malignant cells. Although there are data regarding the molecular pathology of multiple myeloma, the molecular mechanisms of the disease have not been fully elucidated. Aims To investigate the gene expression profiles in bone marrow myeloma cells via RNA-sequencing technology. Study design Cell study. Methods Myeloma cells from four patients with untreated multiple myeloma and B cells from the bone marrow of four healthy donors were sorted using a FACSAria II flow cytometer. The patient pool of myeloma cells and the control pool of B cells were the two comparative groups. A transcriptome analysis was performed and the results were analyzed using bioinformatics tools. Results In total, 18.806 transcripts (94.4%) were detected in the pooled multiple myeloma patient cells. A total of 992 regions were detected as new exon candidates or alternative splicing regions. In addition, 490 mutations (deletions or insertions), 1.397 single nucleotide variations, 415 fusion transcripts, 132 frameshift mutations, and 983 fusions, which were reported before in the National Center for Biotechnology Information, were detected with unknown functions in patients. A total of 35.268 transcripts were obtained (71%) (25.355 transcripts were defined previously) in the control pool. In this preliminary study, the first 50 genes were analyzed with the MSigDB, Enrichr, and Panther gene set enrichment analysis programs. The molecular functions, cellular components, pathways, and biological processes of the genes were obtained and statistical values were determined using bioinformatics tools and are presented as a supplemental file. Conclusion EEF1G, ITM2C, FTL, CLPTM1L, and CYBA are identified as possible candidate genes associated with myelomagenesis.

The aim was to investigate the discriminative value of a wide range of quantitative computed tomography (qCT) parameters in systemic sclerosis (SSc) patients with and without pulmonary fibrosis (PF) and their association with pulmonary function tests (PFTs) and visual fibrosis scores (VFS).Thoracic high-resolution computed tomography (HRCT) images of SSc patients with and without PF were analyzed with Vitrea® Advanced Visualization software. The mean lung attenuation (MLA), skewness, kurtosis, and threshold-based volumes [low-density volume (LDV), medium-density volume (MDV), and high-density volume (HDV)] derived from the attenuation histograms of the right and left lungs were evaluated separately. Visual scores were measured semi-quantitatively and the overall extent of pulmonary parenchymal abnormality was calculated.Forty-one SSc patients with PF (85.4% female; mean age 50.4 ± 15.6 years) were compared with 94 without PF (88.3% female; mean age 50 ± 11.5 years). All qCT parameters were significantly different between those with and without PF (p 0.05). Amongst the qCT measurements, R-MLA, L-MLA, R-MDV, L-MDV, and left total lung volume (L-TLV) correlated with all three of forced vital capacity, carbon monoxide diffusion capacity, and VFS, even after adjustment for sex and age (|r| 0.300 and p 0.05). R-MLA, L-MLA, R-HDV/TLV, and L-HDV/TLV exhibited diagnostic accuracy in discriminating patients with PF (AUC value 0.7).QCT parameters differentiated SSc patients with PF from the ones without and showed a good correlation with VFS. With the application of user-friendly and less operator-dependent software, qCT analysis may become an objective tool for analysis of PF in SSc, complementary to PFTs and VFS. Key Points • Quantitative computed tomography parameters can accurately and objectively differentiate between SSc patients with and without PF. • Furthermore, in SSc patients with fibrosis, a moderate to a high correlation was identified between many of the qCT parameters, PFT results, and VFS.

Background: the course of novel coronavirus disease 2019 (COVID-19) has been of special concern in patients with inflammatory rheumatic diseases (IRDs) due to the immune dysregulation that may be associated with these diseases and the medications used for IRDs, that may affect innate immune responses. Objective: in this cohort study, we aimed to report the disease characteristics and variables associated with COVID-19 outcome among Turkish patients with IRDs. Methods: between April and June, 2020, 167 adult IRD patients with COVID-19 were registered from 31 centers in 14 cities in Turkey. Disease outcome was classified in 4 categories; (i) outpatient management, (ii) hospitalization without oxygen requirement, (iii) hospitalization with oxygen requirement, and (iv) intensive care unit (ICU) admission or death. Multivariable ordinal logistic regression analysis was conducted to determine variables associated with a worse outcome. Results: 165 patients (mean age: 50 ± 15.6 years, 58.2% female) were included. Twenty-four patients (14.5%) recovered under outpatient management, 141 (85.5%) were hospitalized, 49 (30%) required inpatient oxygen support, 22 (13%) were treated in the ICU (17 received invasive mechanic ventilation) and 16 (10%) died. Glucocorticoid use (OR: 4.53, 95%CI 1.65-12.76), chronic kidney disease (OR: 12.8, 95%CI 2.25-103.5), pulmonary disease (OR: 2.66, 95%CI 1.08-6.61) and obesity (OR: 3.7, 95%CI 1.01-13.87) were associated with a worse outcome. Biologic disease-modifying antirheumatic drugs (DMARDs) do not seem to affect COVID-19 outcome while conventional synthetic DMARDs may have a protective effect (OR: 0.36, 95%CI 0.17-0.75). Estimates for the associations between IRD diagnoses and outcome were inconclusive. Conclusions: among IRD patients with COVID-19, comorbidities and glucocorticoid use were associated with a worse outcome, while biologic DMARDs do not seem to be associated with a worse outcome., NA

Objective: To compare the treatment outcomes of TNF inhibitors and tocilizumab (TCZ) in patients with Takayasu arteritis. Methods: Takayasu arteritis patients who were refractory to conventional immunosuppressive (IS) drugs and received biologic treatment were included in this multicenter retrospective cohort study. Clinical, laboratory and imaging data during follow-up were recorded. Remission, glucocorticoid (GC) sparing effect, drug survival was compared between TNF inhibitor and TCZ treatments. Also, a subgroup matched comparison was performed between groups. Results: One hundred and eleven (F/M: 98/13) patients were enrolled. A total of 173 biologic treatment courses (77 infliximab, 49 TCZ, 33 adalimumab, 9 certolizumab, 3 rituximab, 1 ustekinumab and 1 anakinra) were given. Tocilizumab was chosen in 23 patients and TNF inhibitors were chosen in 88 patients as first line biologic agent. Complete/partial remission rates between TCZ and TNF inhibitors were similar at 3rd month and at the end of the follow-up. GC dose decrease (

WOS: 000437779600001 PubMed ID: 30344882 Introduction: The prevalence of Sjogren's syndrome (SS) in patients with the diagnosis of SpA has been reported to be higher than normal population. Yet, the vice-versa is unclear. In this study, we aimed to investigate the prevalence of IBP, radiologic sacroiliitis and SpA in patients with primary SS. Methods: 85 patients followed at the rheumatology clinics of the Marmara and Kocaeli Universities with the diagnosis of primary SS between November 2011 and August 2012 were included in this study. The control group consisted of 100 age-and gender-matched patients. Inflammatory back pain and axial SpA were diagnosed according to the assessment of spondylo arthritis International Society (ASAS) criteria. Results: 83 patients were (97%) female and 2 (3%) were male. Mean age of the patients was 49.1 (+/- 11) years. Mean disease duration was 7.3 (+/- 4) years. The patient and control groups were comparable in terms of age and gender (p>0.05). Inflammatory back pain was observed in 21 (24.7%) of 85 primary SS patients and in 4 (4%) of 100 control subjects (p

OBJECTIVES To investigate lung volume and density in patients with SSc and changes in these parameters because of PF, using a software-aided image quantification method, and compare this with a matched healthy control group. METHODS Thoracic high-resolution computed tomography (HRCT) images of patients and controls were analysed using Myrian XP Lung 3D software. Right, and left lung densities and volumes were calculated separately by a blinded operator. Results were analysed between subgroups to investigate associations with the clinical features. RESULTS A total of 135 patients with SSc and 38 healthy controls (HC) were included. Characteristics of the SSc patients were 94 (69.6%) without PF, 85.4% female, mean age 49.8 (15.4) years; 41 (30.4%) with PF, 88.3% female, mean age 50.2 (11.5) years, and HC group were 89.5% Female, mean age 52.2 (5.8) years. The right and left lung densities were significantly higher, and right and left lung volumes were significantly lower in the SSc patients with signs of fibrosis than those without and HC (P

Spondyloenchondrodysplasia (SPENCD) is a rare skeletal dysplasia characterized with platyspondyly and metaphyseal lesions of the long bones mimicking enchondromatosis, resulting in short stature. SPENCD often coexists with neurologic disorders and immune dysregulation. Spasticity, developmental delay and intracranial calcification are main neurologic abnormalities. Large spectrum of immunologic abnormalities may be seen in SPENCD, including immune deficiencies and autoimmune disorders with autoimmune thrombocytopenia and systemic lupus erythematosus as the most common phenotypes. SPENCD is caused by loss of tartrate-resistant acid phosphatase (TRAP) activity, due to homozygous mutations in ACP5, playing a role in non-nucleic acid-related stimulation/regulation of the type I interferon pathway. We present two siblings, 13-year-old girl and 25-year-old boy with SPENCD, from consanguineous parents. Both patients had short stature, platyspondyly, metaphyseal changes, spastic paraparesis, mild intellectual disability, and juvenile-onset SLE. The age at disease-onset was 2 years for girl and 19 years for boy. Both had skin and mucosa involvement. The age at diagnosis of SLE was 4 years for girl, and 19 years for boy. The clinical diagnosis of SPENCD was confirmed by sequencing of ACP5 gene, which revealed a homozygous c.155A > C (p.K52T), a variant reported before as pathogenic. Juvenile-onset SLE accounts for about 15–20% of all SLE cases. But, the onset of SLE before 5-years of age and also monogenic SLE are rare. Our case report and the literature review show the importance of multisystemic evaluation in the diagnosis of SPENCD and to remind the necessity of investigating the monogenic etiology in early-onset and familial SLE cases.

Background Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by various clinical presentations. Human immune deficiency virus (HIV) causes acquired immune deficiency syndrome (AIDS) in case of progression of the infection. Patients with HIV can present different rheumatologic findings including arthralgia, arthritis, myalgia, myositis, vasculitis, and gout. We herein present a patient mimicking SLE who was diagnosed with HIV. Methods A 40-year-old man presented with a 3-month history of oral lesions and a 2-month history of blurry vision, vertigo, speech difficulty, and ataxic gait. His past medical history was unremarkable. His vital findings were within normal ranges. There were two oral lesions that were greater than 10 mm in diameter localized on the hard palate and tongue. Cerebellar tests including gait, finger-to-nose, and heel-to-shin were abnormal. He could not walk in tandem gait. However, muscle strength and sensory exam were normal. On laboratory outcomes, fasting blood glucose, blood urea nitrogen, creatinine, and thyroid-function tests were normal. The rest of laboratory data were as follows: ALT 129 U/L, AST 102 U/L, GGT 72 U/L, hemoglobin 12.3 mg/L, WBC 3.6×103/mcL, neutrophil count 1.8×103/mcL, lymphocyte count 1.2×103/mcL, CRP 1.5 mg/dl (normal, ≤5 mg/dl), ESR 42 mm/h. Cranial MRI was reported as multiple hyperintense spots located on supratentorial white matter, corpus callosum, and brainstem on standard T2-weighted MRI sequence. On neurological consultation, these lesions were interpreted as encephalitis. Additionally, he was consulted to Ophthalmologist due to blurry vision. No pathological finding was found. He was also for autoimmune disorders causing cerebral involvement. Thus, ANA, ENA, anti ds DNA, ANCA were investigated. All autoantibodies, hepatitis screening, CMV, EBV, parvovirus B 19 were found negative. On the other hand, HIV positivity was detected by ELISA. Consequently, the patient was transferred to department of Infectious diseases. Conclusion HIV causes autoimmune and systemic disorders via triggering immune dysregulation. The frequency of these autoimmune diseases has ranged from 1% to 60% according to literature. Both HIV and the treatment of HIV can cause rheumatologic findings.

Objectives Diagnosing Behçet’s disease (BD) is a challenge, especially in countries with a low prevalence. Recently, venous wall thickness (VWT) in lower extremities has been shown to be increased in BD patients. In this study, we aimed to investigate the diagnostic performance of common femoral vein (CFV) thickness measurement in BD and whether it can be used as a diagnostic tool. Methods . Patients with BD (n = 152), ankylosing spondylitis (n = 27), systemic vasculitides (n = 23), venous insufficiency (n = 29), antiphospholipid syndrome (APS; n = 43), deep vein thrombosis due to non-inflammatory causes (n = 25) and healthy controls (n = 51) were included in the study. Bilateral CFV thickness was measured with ultrasonography by a radiologist blinded to cases. Results Bilateral CFV thickness was significantly increased in BD compared with all control groups (P 0.95 for the cut-off value (0.5 mm). This cut-off value also performed well against all control groups with sensitivity rates >90%. The specificity rate was also >80% in all comparator groups except APS (positive predictive value: 79.2–76.5%, negative predictive value: 92–91.8% for right and left CFV, respectively). Conclusion Increased CFV thickness is a distinctive feature of BD and is rarely present in healthy and diseased controls, except APS. Our results suggest that CFV thickness measurement with ultrasonography, a non-invasive radiological modality, can be a diagnostic tool for BD with sensitivity and the specificity rates higher than 80% for the cut-off value ≥0.5 mm.

Objective Familial Mediterranean Fever (FMF) is an autoinflammatory disease that is commonly present with recurrent episodes of fever, peritonitis, pleuritis or arthritis. Enthesitis and sacroilitis can also be seen in FMF. Spondylitis is a less common manifestation of joint involvement in FMF and there are controversial publications about whether this involvement is FMF-related or coincidentally. The aim of this study was to provide a comparison between ankylosing spondylitis (AS) patients and FMF patients with AS. Methods A total of 404 patients who 360 of them was AS and 44 was FMF patients with AS (in accordance with Tel Hashomer) patients with AS (in accordance with modified New York criteria) were included in this study. All cases were evaluated retrospectively and patient's demographic and clinical data were recorded. Results The mean age was 34.5 ± 8.6 years and 61.4% of patients were female in FMF group. In AS group, the mean age was 41.2 ± 10.8 years and 67.8% of patients were male. In AS group, 92% of patients had inflammatory back pain, 51% had hip pain, 30% had heel pain, 14% had peripheral arthritis and 11% had uveitis. In FMF group, 98% of patients had inflammatory back pain, 59% had hip pain, 48% had heel pain, 43% had peripheral arthritis and 4.5% had uveitis. Syndesmophyte and enthesitis on X-ray were seen in 18% and 22% of AS patients, and 7% and 41% of FMF patients with AS, respectively. There were significant differences between AS patients and FMF patients with AS in terms of heel pain (P: .017), peripheral arthritis (P: .000) and enthesitis (P: .006). Conclusion Peripheral arthritis and enthesitis were more frequent, and uveitis and syndesmophyte were less frequent in FMF patients with spondylitis than AS patients. When we look at gender differences, clinical and genetic features, it seems to be different condition from AS.

Aim: Analysis of genes that play roles in multiple myeloma pathogenesis and their pathways are current research topics. We aimed to detect expression of some genes in ErbB and insulin signaling pathways. Methods: Bone marrow samples were taken from three healthy volunteers and 17 treatment-naive patients. Firstly RNA isolation was made and then cDNA were synthesized. There are eight genes that are related to ErbB and insulin signaling pathways. Specific primers for these genes were designed. Gene expression analysis was performed by the real-time polymerase chain reaction method. Results: In the patient group, expressions of MTOR, RPTOR, PIK3CA, AKT1, ErbB4, PRKAR2A and PRKACB genes were detected to be 3-10 times up-regulated than in control group. There were no differences in the expression levels of RICTOR and GYS1 genes between control group and patient group. GYS1, PRKACB and PRKAR2A genes have been analyzed for the first time. Conclusion: In this study, PRKAR2A and PRKACB genes expressions were detected to be upregulated and this has not been reported in the literature before. MTOR, RPTOR, PIK3CA, AKT1, and ErbB4 genes expression were detected to be upregulated as has been reported in the literature. All these results will be useful to understand the pathogenesis of multiple myeloma.

Chronic lymphocytic Leukemia (CLL) is the most common form of leukemia in adults. Clinical findings may broad range vary. Detecting some deletions using the FISH method may help us to foresee the progression of the disease and to choose a better treatment method in healing the patient. In this case report, we will present you a CLL patient with t(7;14), t(14;19) and 17p deletions, which are known for bad prognosis, developing autoimmune hemolytic anemia which is refractor to the treatment. This patient unfortunately died due to a clinical form of hemophagocytic syndrome including prolymphocytic transformation.

Background Oral white sponge nevus (WSN) is a rare autosomal dominant benign condition, characterized by asymptomatic spongy white plaques. Mutations in Keratin 4 (KRT4) and 13 (KRT13) have been shown to cause WSN. Familial cases are uncommon due to irregular penetrance. Thus, the aim of the study was: a) to demonstrate the clinical and histopathological features of a three-generation Turkish family with oral WSN b) to determine whether KRT4 or KRT13 gene mutation was the molecular basis of WSN. Material and Methods Out of twenty members of the family ten were available for assessment. Venous blood samples from six affected and five unaffected members and 48 healthy controls were obtained for genetic mutational analysis. Polymerase chain reaction was used to amplify all exons within KRT4 and KRT13 genes. These products were sequenced and the data was examined for mutations and polymorphisms. Results Varying presentation and severity of clinical features were observed. Analysis of the KRT13 gene revealed the sequence variant Y118D as the disease-causing mutation. One patient revealed several previously unreported polymorphisms including a novel mutation in exon 1 of the KRT13 gene and a heterozygous deletion in exon 1 of KRT4. This deletion in the KRT4 gene was found to be a common polymorphism reflecting a high allele frequency of 31.25% in the Turkish population. Conclusions Oral WSN may manifest variable clinical features. The novel mutation found in the KRT13 gene is believed to add evidence for a mutational hotspot in the mucosal keratins. Molecular genetic analysis is required to establish correct diagnosis and appropriate genetic consultation. Key words:White sponge nevus, leukokeratosis, oral mucosa, keratins, mutation.

Background:Tocilizumab (TCZ) is a human anti-interleukin (IL)-6 receptor antibody approved in Turkey for the treatment of rheumatoid arthritis (RA).Objectives:In this study our purpose was to describe the disease activity, quality of life (QoL), and retention rate in RA patients who were prescribed TCZ as first-line biologic treatment in a real-world setting.Methods:Anonymized patient registry of TURKBIO was used based in a national, multicenter, and retrospective context. We conducted a search in the registry between years 2013 and 2020 and included adult RA patients who were prescribed with TCZ as their first-line biologic treatment with a post-TCZ follow-up of at least 6 months. CDAI, DAS28-(ESR), and HAQ-DI scores in 6, 12, and 24 months were obtained. Pairwise comparison was carried out for survey scores across baseline and timepoints. Subgroup analysis for route of TCZ administration was performed. EULAR response criteria were used for response evaluation. Retention of TCZ was evaluated by Kaplan-Meier analysis.Results:Overall,130 patients with a mean RA duration of14 years were included in the study. 87.7% of the patients were female and mean age was53 (SD; 15.0). Median duration of follow-up was 18.5 months. Majority (90.8%) of patients were given tocilizumab via intravenous route at baseline. Number of patients with ongoing TCZ treatment and follow-up at 6, 12, and 24 months were 121 (93%), 85 (65%), and 46 (35%), respectively. Remission rates at 6, 12, and 24 months per CDAI (Conclusion:TCZ as a first-line biologic treatment was found to be clinically effective in this real-world study with a high retention rate. These results are in line with the results gathered from previous TCZ controlled and real-life studies in which TCZ was found clinically safe and effective.References:[1]Haraoui B, Casado G, Czirjak L, Taylor A, Dong L, Button P, Luder Y, Caporali R. Tocilizumab Patterns of Use, Effectiveness, and Safety in Patients with Rheumatoid Arthritis: Final Results from a Set of Multi-National Non-Interventional Studies. Rheumatol Ther. 2019 Jun;6(2):231-243.[2]Favalli EG, Raimondo MG, Becciolini A, Crotti C, Biggioggero M, Caporali R. The management of first-line biologic therapy failures in rheumatoid arthritis: Current practice and future perspectives. Autoimmun Rev. 2017 Dec;16(12):1185-1195.[3]Haraoui B, Jamal S, Ahluwalia V, Fung D, Manchanda T, Khraishi M. Real-World Tocilizumab Use in Patients with Rheumatoid Arthritis in Canada: 12-Month Results from an Observational, Noninterventional Study. Rheumatol Ther. 2018 Dec; 5(2): 551–565.Disclosure of Interests:Ayten Yazici Speakers bureau: PFIZER, AbbVie, NOVARTIS, Özlem Özdemir Işik: None declared, Ediz Dalkiliç Speakers bureau: AbbVie, UCB Pharma, PFIZER, Roche, MSD, NOVARTIS, Süleyman Serdar Koca Speakers bureau: MSD, NOVARTIS, GILEAD, PFIZER, ABDI IBRAHIM, UCB Pharma, AMGEN, SANOFİ, Yavuz Pehlivan Speakers bureau: PFIZER, NOVARTIS, MSD, CELLTRION, Consultant of: PFIZER, Soner Şenel: None declared, Nevsun Inanc Speakers bureau: NOVARTIS, PFIZER, ABDI IBRAHIM, JANNSEN, Paid instructor for: NOVARTIS, PFIZER, ABDI IBRAHIM, JANNSEN, Consultant of: NOVARTIS, PFIZER, ABDI IBRAHIM, JANNSEN, Grant/research support from: NOVARTIS, PFIZER, ABDI IBRAHIM, JANNSEN, Servet Akar Speakers bureau: LILLY, MSD, NOVARTIS, GILEAD, PFIZER, ABDI IBRAHIM, JANNSEN, UCB Pharma, AMGEN, Paid instructor for: LILLY, NOVARTIS, GILEAD, PFIZER, ABDI IBRAHIM, UCB, AMGEN, Grant/research support from: PFIZER, Sema Yilmaz: None declared, Özgül Soysal Gündüz: None declared, Ayse Cefle Speakers bureau: UCB Pharma, PFIZER, MSD, AbbVie, AMGEN, NOVARTIS, Fatos Onen Speakers bureau: AbbVie, LILLY, MSD, NOVARTIS, GILEAD, PFIZER, ABDI IBRAHIM, JANNSEN, UCB Pharma, AMGEN, İbrahim Etem-MENARINI, Paid instructor for: AbbVie, LILLY, NOVARTIS, GILEAD, PFIZER, ABDI IBRAHIM, UCB Pharma, AMGEN, İbrahim Etem-MENARINI, Grant/research support from: PFIZER

Background:Currently, biologic treatments are used effectively in patients with psoriatic arthritis (PsA).Objectives:The aim of this study was to evaluate and compare long-term drug survival of the first biologic treatments including adalimumab, certolizumab, etanercept, golimumab, infliximab, secukinumab and ustekinumab in patients with PsA.Methods:PsA patients, electronically registered at each visit in the TURKBIO database between 2011 and 2019 were included in the study. PASW 18.0 for Windows was used for statistical analysis. Drug survival rates were calculated by Kaplan Meier method.Results:355 patients (227 women; axial PsA = 48, peripheral PsA = 307) were included in the study (Table 1). Adalimumab was the most commonly used first biologic treatment (n=125; 37.6%). The rate of drug survival was found to be 0.75 at month 60 in patients receiving the first biologic treatment (Figure 1). There was no significant difference in drug survival rate between tumor necrosis factor alpha inhibitor (TNFi) and non-TNFi biologic drugs (p=0.56). No difference was also found in drug survival rates between each biologic treatment.Table 1.Initial demographic and clinical datas of patients with PsAPsA Patients (n=355)Females, n (%)227 (63,9)Age of diagnosis, years*34,6 (27-42)CRP baseline*6 mg/ L (3-15)ESR baseline*24 mm/h (10-38)Smoking, n (%)Current99 (28,5)Never192 (55,3)Previous56 (16,2)HLA B27 positivity,n (%)41 (26,4)First biologic agent, n (%)-TNFi332 (95,4)AdalimumabEtanercept125 (37,6)80 (24,1)Golimumab52 (15,6)Certolizumab44 (13,3)Infliximab31 (9,4)- Other biologic agents16 (4,6)Secukinumab13 (81,3)Ustekinumab3 (18,7)*median (min-max)Conclusion:The results of this study establish that more than half of patients with PsA can remain in their initial biologic treatment over a long term. It has been observed that the choice of biologic treatment did not effect the drug survival in PsA.Disclosure of Interests:None declared

Background: As a result of arterial ischemia, the frequencies of hypertension (HT), ischemic heart disease, congestive heart failure and atherosclerosis have been shown to increase and contribute to mortality in patients with Takayasu’s arteritis (TAK). Determining cardiovascular disease (CVD) and associated risk factors in TAK is important for a comprehensive treatment approach and better disease prognosis. Data about the effect of metabolic syndrome (MetS) which is known as a risk factor for CVD on TAK are limited. Objectives: The aim of this study was to determine the prevalence of MetS in patients with TAK and its effect on CVD and cumulative organ damage. Methods: A total of 122 TAK patients, followed by Turkish Takayasu Study Group in 7 tertiary Centers and diagnosed according to the 1990 ACR criteria were consecutively assessed for cumulative organ damage (VDI score), history of CVD and MetS as defined by the National Cholesterol Educational Program Adult Treatment Panel III (NCEP ATP III). CVD was defined as coronary artery disease or cerebrovascular event (myocardial infarction or stroke). Results: Eighty-seven percent of patients were female and the median age was 39 (17-65) years. The frequency of MetS was 14.7% and CVD was 13.1%. The median age, disease duration, smoking prevalence and CVD were found slightly higher in MetS group, without reaching statistical significance. There were no differences in VDI score between the groups (Table 1). Conclusion: MetS frequency in our TAK patients was observed to be less than the normal population data obtained from METSAR (Turkish MetS study in normal population) in Turkey (female: 39.6%, male: 28%). The discrepancy with SLE, which is another inflammatory autoimmune disease having a higher frequency of MetS related with organ damage, may be explained with the potentially more severe disease course in SLE patients requiring higher cumulative doses of glucocorticoids (1). Reference [1] Demir S, Artim-Esen B, Sahinkaya Y, Pehlivan O, Alpay-Kanitez N, Omma A, et al. Metabolic syndrome is not only a risk factor for cardiovascular diseases in systemic lupus erythematosus but is also associated with cumulative organ damage: a cross-sectional analysis of 311 patients. Lupus. 2016;25:177-84. Disclosure of Interests: Nilufer Alpay Kanitez: None declared, Sema Kaymaz Tahra: None declared, Ayten Yazici: None declared, Ayse Cefle: None declared, Mete Kara: None declared, Handan Yarkan-Tugsal: None declared, Onay Gercik: None declared, Servet Akar Grant/research support from: MSD, Abbvie, Roche, UCB, Novartis, Pfizer, Amgen, Consultant for: MSD, Abbvie, Roche, UCB, Novartis, Pfizer, Amgen, Speakers bureau: Pfizer, Fatos Onen: None declared, Kenan Aksu: None declared, Gokhan Keser: None declared, Cemal Bes: None declared, Sevil Kamali: None declared, Fatma Alibaz-Oner: None declared, Haner Direskeneli: None declared

Background The first symptoms of ankylosing spondylitis (AS) patients usually begin prior to 45 years, but can occur later in life. Objectives The purpose of this study is to evaluate the efficacy and safety of anti-TNFα treatment in late-onset AS (LoAS) patients in comparison to those with adult onset AS (AoAS). Methods We studied AS patients in TURKBIO registry between the dates of January 2011 and November 2018. All the patients fulfilled the modified New York criteria for AS 1 and were classified into 2 groups based on their age at symptom onset: AoAS (age>16 but ≤45 years); and LoAS (age>45 years). In both groups, the following data were compared: (1) epidemiological variables (2) clinical manifestations, including signs and symptoms at diagnosis; (3) laboratory results (4) disease activity markers and follow-up parameters (BASDAI, ASDAS-CRP and HAQ); (5) previous and current treatments (6) adverse events. Results A total of 2551 AS patients (91,1% with AoAS and 8.9% with LoAS) were included in the study. LoAS group had more female patients, older age, shorter disease duration and diagnostic delay, higher initial ESR and less HLA-B27 positivity compared to the AoAS (Table 1). Peripheral arthritis (not statistically significant) and dactylitis was seen more common in the LoAS. The frequency of other involvements was similar between the groups (Table1). The frequency of using drugs was similar between each groups although the use of glucocorticoids and sulphasalazine was more common in the LoAS. Switching from the first anti-TNFα treatment to the second one was more common in the AoAS. However, there was found no significant difference between the two groups in 2 or more switch ratios (Table 1). At the latest visit after the anti-TNFα therapy, the mean improvement in BASDAI was significantly higher in the AoAS (Table 2). A total of 10 (4.4%) serious adverse events were reported in LoAS and 39 (1.7%) in AoAS patients in the follow-up (HR: 2.62; 95% CI: 1.32–5.18). Severe infections were the most commonly seen serious adverse events (1.3% in LoAS and 0.8% in AoAS), followed by allergic reactions (0.9% in LoAS and 0.3% in AoAS). Tuberculosis was observed in 2 patients (0.9%) in LoAS and 9 (0.4%) in AoAS, malignancy in 3 patients (1.3%) in LoAS and 6 (0.3%) in AoAS. Conclusion Our data showed that almost 8.9% of the patients with AS had late-onset of symptoms. The results suggested that LoAS patients might have different demographic, clinical features, disease activity parameters at baseline. The frequency of anti-TNFα use and response rate to the treatment was also similar in LoAS to those in AoAS patients. The LoAS patients seem to have more common severe adverse events compared to the AOAS patients possibly related to their older age. References [1] Van der Linden S, Valkenburg HA. Evaluation of diagnostic criteria for AS. Arthritis Rheum1984; 27: 361–368. Disclosure of Interests Sadettin Uslu: None declared, Gercek Can: None declared, Ayse Cefle: None declared, Sema Yilmaz: None declared, Sinem Burcu Kocaer: None declared, Tuba Yuce Inel: None declared, Semih Gulle: None declared, Suleyman Serdar Koca: None declared, Servet Yolbas: None declared, Mehmet Akif Ozturk: None declared, Soner Senel: None declared, Nevsun Inanc: None declared, Ediz Dalkilic Grant/research support from: MSD and Abbvie, Consultant for: MSD, Abbvie,Roche, UCB, Pfizer and Novartis, Speakers bureau: MSD, Abbvie,Roche, UCB, Pfizer and Novartis, Ozgul Soysal: None declared, abdurrahman tufan: None declared, Servet Akar Grant/research support from: MSD, Abbvie, Roche, UCB, Novartis, Pfizer, Amgen, Consultant for: MSD, Abbvie, Roche, UCB, Novartis, Pfizer, Amgen, Speakers bureau: Pfizer, Merih Birlik: None declared, Ismail Sari: None declared, Nurullah Akkoc: None declared, Fatos Onen: None declared

Background Patients with Sjogren’s syndrome (SS) have symptoms such as vaginal dryness and dyspareunia. Objectives In this study we aimed to present of primary SS (pSS) and secondary SS (sSS) patient‘s gynecological symptoms and effects of the disease on sexuality. Methods 60 pSS, 42 sSS, 52 healthy controls (HC) were interviewed. It was asked questions about sexuality, SF-36, HAD scale, pSS and sSS patients were also administered HAQ and Modified Hiil questionnaire¹. Results The mean age of the patients was 52 ± 11 years in the pSS, 54 ± 11years in the sSS and 46 ± 9 years in the HC. Although there was no significant difference in term of age in pSS and sSS groups, mean age was lower in HC group. There were no significant differences in SF-36 mental index score, SF-36 physical index score, HAD-Anxiety score and HAD-Depression score among 3 groups. 62% of patients in the pSS, 79% in the sSS and 33% in HC were in menopause. Vaginal and vulvar dryness were significantly higher in SS, especially in the pSS than HC. The proportion of sexually active women was lower in sSS group. Spontaneous genital pain and dyspareunia were found to be high in pSS and it was statistically significant. Decreased sexual desire was significantly higher in SS groups (Table1). HAQ score was significantly lower in pSS group than sSS group. Dyspareunia, dysuria, vaginal dryness and fatigue were significantly higher in pSS (Table2). There was no significant difference between two groups in terms of the effect of vulvar, vaginal dryness, dyspareunia, decreased sexual desire, myalgia, arthralgia and fatigue on sexuality In the pSS group, it was seen that disease had a negative effect on sexuality. There were no significant differences between the two groups when asked whether they enjoyed sexuality and the sexual problems create problems between their partners. In both groups, 97% of patients stated that they had not been questioned about their sexuality before. 80% of pSS patients and 88% of sSS patients stated that they did not talk about sexuality problems. Conclusion Gynecological and sexual problems are seen in SS patients. Menopause also contributes to this situation. Patients should be informed about these problems and directed to gynecologists when necessary, and enough time should be reserved as we do. References [1] S. Maddali Bongi at all.Gynaecological Symptoms and Sexual Disability in Women with Primary Sjogren’s Syndrome and Sicca Syndrome.Clinical and Experimental Rheumatology 2013; 31: 683-690 Disclosure of Interests None declared

Background Takayasu’ arteritis (TAK) is a rare vasculitis characterized by inflammation and obliteration of intermediate to large-size arteries. Even though more than 50% of patients with TAK have pulmonary artery involvement, non-vascular involvement and symptoms are uncommon. Objectives We aimed to investigate the frequency of non-vascular pulmonary involvement in TAK. Methods We assembled a retrospective cohort of patients with TAK from six different centers in Turkey. The demographics, clinical characteristics, treatment and outcomes of patients were abstracted from medical records, and the computed tomography findings were evaluated for pulmonary manifestations. Results As of January 2019, 197 TAK patients were recruited (mean age: 42.7±13.9 years [min-max: 17-75]) to the cohort, and 88.3% of them were female. Twenty-four patients had cough and/or dyspnea and four had hemoptysis as pulmonary symptoms. In CT assessment, parenchymal infiltrations were present in four (2%), pleural effusion in five (2.5%), nodule/cavity in one (0.5%), and pulmonary hemorrhage in one patient (0.5%). The patient who had pulmonary hemorrhage had also pleural effusion at the same time. In the whole cohort, 11.2% of patients (n=22) had pulmonary hypertension (PAH), three of them had cough and/or dyspnea and four of them had hemoptysis as a pulmonary symptom. Among patients with PAH, any pulmonary involvement in CT was more frequent compared to the rest of the patients (22.7% vs 5.1%, p Conclusion In this first assessment of Turkish TAK cohort, we observed non-vascular pulmonary involvement in about 5% of our patients and half of them were pleural effusions. The second most common manifestation was parenchymal infiltration with a frequency of 2%. Although rare, non-vascular pulmonary manifestations should also be investigated in TAK patients, especially in patients with pulmonary hypertension. References [1] Nakajima N. Takayasu Arteritis: Consideration of pulmonary involvement. Ann Vasc Dis2008;1(1):7-10. [2] Elsasser S, Soler M, Bollinger CT, et al. Takayasu disease with predominant pulmonary involvement. Respiration2000;67(2):213-5. Disclosure of Interests Ayten Yazici: None declared, Ayse Cefle: None declared, Sema Kaymaz Tahra: None declared, Nilufer Alpay Kanitez: None declared, Mete Kara: None declared, Onay Gercik: None declared, Handan Yarkan Tugsal: None declared, Fatos Onen: None declared, Servet Akar Grant/research support from: MSD, Abbvie, Roche, UCB, Novartis, Pfizer, Amgen, Consultant for: MSD, Abbvie, Roche, UCB, Novartis, Pfizer, Amgen, Speakers bureau: Pfizer, Kenan Aksu: None declared, Gokhan Keser: None declared, Fatma Alibaz-Oner: None declared, Haner Direskeneli: None declared

Infertility is an important health problem affecting 15% of couples worldwide. Intellectual disability (ID) is characterized with significant impairment of intellectual function, adaptive daily life skills and social skills. Insertion is a rare chromosomal rearrangement causing infertility and ID. Here, we report a 39-year-old man presenting with primary infertility and mild ID. The patient’s spermiogram was consistent with azoospermia. Conventional cytogenetic analysis showed a novel inversion/insertion type of chromosomal aberration involving chromosomes 18 and 2: 46, XY, inv ins(18;2)(q11.2;q13q22). We carried out the array comparative genomic hybridization analysis to confirm the cytogenetic findings. Y micro-deletion analysis demonstrated that the AZF region as intact. We suggest that the novel insertion found in this case [46, XY, inv ins(18;2)(q11.2;q13q22)] may have caused infertility and mild ID in our patient. To the best of our knowledge, this chromosomal insertion has not previously been reported.

Background:Behçet’s disease (BD) is a vasculitic multisystem inflammatory disorder. It may also involve the skin, mucosa, eyes, blood vessels, joints, gastrointestinal system, and central nervous system (CNS).Objectives:In this study, we aimed to present CNS involvement data in patients followed up with a diagnosis of BD.Methods:The clinical, demographic, laboratory and medication data of 394 patients who were followed up with a diagnosis of BD in our rheumatology outpatient clinic between 2000 and 2020 were retrospectively evaluated.Results:CNS involvement was detected in %5.6(24) patients who were followed up with a diagnosis of BD. 66.7% of the patients were male, and their mean diagnosis age was 25.1±8.2 years, mean CNS involvement age was 28.39±9.6 years. Neurological symptoms occurred in an average of 3.3 years after the diagnosis of BD. Parenchymal involvement was present in 54.2% of the patients with CNS involvement, 45.8 % had cerebral venous thrombosis. Oral apthous ulcer was found in 91.7 % of the patients, genital ulcer in 70.8%, pathergy positivity in %45.8 papulopustular lesion in %37.5, erythema nodosum in %45.8. Patients with CNS involvement had headache, vision loss, diplopia, hemiparesis, epilepsy, proptosis, and ataxic gait and walking difficulty in 66.6%, 12.5%, 25%, 12.5%, 8.3%, 8.3% and 12.5%, respectively. Patients with and without CNS involvement were compared in terms of clinical findings and medications. A significant difference was observed in terms of cardiac involvement (Table 1). While one of the 2 patients with cardiac involvement had a thrombus in the right ventricle, the other had pericardial effusion. The patient with cardiac thrombus also had cerebral venous thrombus. Steroid, azathioprine, cyclophosphamide treatments have been used at a higher in patients with CNS involvement. In addition, the patients with parenchymal and cerebral venous involvement were compared in terms of clinical, demographics findings and medications. The presence of papulopustular lesions (9.1% vs 57.1%) and pathergy positivity (18.2% vs 71.4%) were higher in patients with parenchymal involvement (p:0.033, p: 0.020, respectively).Table 1.Comparison of data of patients with and without CNS involvementn (%)CNS Involvement (+)n:24CNS Involvement (-)n:370PGender0.396 Female8(33.3)164(44.3) Male16(66.7)206(55.7)Oral Aphthous Ulcer22(91.7)357(96.5)0.230Genital Ulcer17(70.8)239(64.6)0.661Papulopustular lesion9(37.5)120(32.4)0.655Erythema Nodosum11(45.8)139(37.6)0.516Pathergy11(45.8)174(47)0.988Uveitis9(37.5)129(34.9)0.827Retinal Vasculitis1(4.2)10(2.7)0.504Arthritis3(12.5)95(25.7)0.221Deep Venous Involvement6(25)59(15.9)0.256Artery Occlusion1(4.2)8(2.2)0.436Arterial Aneurysm1(4.2)14(3.8)1GIS involvement2(8.3)15(4.1)0.277Cardiac involvement2(8.3)4(1.1)0.046Conclusion:It has been reported that neurological symptoms occur in an average of 2.5 to 6.5 years after the diagnosis of BD. On the other hand, it has been stated that neurological complications may be the first involvement in 3-33% of the cases and this situation will cause diagnostic difficulties1. These data are consistent with our study.References:[1]Noel N, Drier A, Wechsler B, ve ark. Neurological manifestations of Behcet’s disease. Rev Med Interne 2014;35(2):112–120.Disclosure of Interests:None declared

Background:Behcet’s Disease (BD) is a systemic variable vessel vasculitis that involves the skin, mucosa, joints, eyes, arteries, veins, nervous system and the gastrointestinal system.Objectives:In this study we aimed to present variety of involvements in patients who were followed up in our outpatient clinic with a diagnosis of BD.Methods:Data of 394 patients diagnosed with BD between 2000-2020 were retrospectively reviewed clinical, demographic characteristics and systemic involvements.Results:In our study 43.7% of BD patients were female, 56.3% were male and the mean age was 40±11years, disease average age of onset 36.5±10.6, disease duration was 12.8±6.8years. It was observed mucocutaneus involvement 98% of the patients, uveitis in 35%, retinal vasculitis in 2.8%, arthritis in 24.9%, arterial occlusion in 2.3%, arterial aneurysm in 3.8%, venous involvement in 19.8%, gastrointestinal (GIS) involvement in 4.3%, cardiac involvement in 1.5%, and cranial involvement 7.1 (Table 1).Table 1.The Data of Behçet Diseasen (%)n= 394GenderFemale172 (43.7)Male222 (56.3)Family History48 (12.2)Fever & Weight Loss21 (5.3)Mucocutaneus involvement386 (98)Oral Aphthous Ulcer379 (96.2)Genital Ulcer256 (65)Papulopustular lesions129 (32.7)Erythema Nodosum-like lesions150 (38.1)Skin Pathergy Reaction185 (47)Uveitis138 (35)Retinal Vasculitis11 (2.8)Venous involvement76 (17.6)Thrombophlebitis30 (7.6)67 (17)Deep venous thrombosisArthritis98 (24.9)Monoarthritis74 (75.5)Oligoarthritis21 (21.4)Sacroiliitis3 (3.0)Artery Occlusion9 (2.3)Arterial Aneurysm15 (3.8)GIS involvement17 (4.3)İleum9 (2.3)Colon2 (0.5)Rectum1 (0.3)İleocolonic4 (1)Cardiac involvement6 (1.5)Pericarditis2 (0.5)Ventricular thrombosis3 (0.7)Atrial thrombosis1 (0.2)Cranial involvement24 (5.6)Parenchymal involvement13 (4.6)Cerebral Venous Thrombosis11 (2.8)Pulse steroid15 (3.8)1mg/kg steroid48 (12.2)Infliximab13 (3.3)Azathioprine184 (46.7)Cyclophosphamide31 (7.9)When all patients evaluated in terms of renal findings, proteinuria was observed in 5 patients and hematuria was observed in 2 patients. 3 patients had proteinuria over than 500mg/day. Their renal biopsy findings; 2 of them were nonspecific involvements and one of them was minimal mesangioproliferative changes.Conclusion:As a multi-system disease, general data have been presented, as clinical symptoms involve almost all systems of the body (1).References:[1]Behcet’s disease Fereydoun Davatchi 1Int J Rheum Dis.2014 May;17(4):355-7. doi: 10.1111/1756-185X.12378.Disclosure of Interests:None declared

Background:Behçet’s disease (BD) is a vasculitic multisystem inflammatory disorder. It may also involve the skin, mucosa, eyes, blood vessels, joints, gastrointestinal system, and central nervous system.Objectives:In this study, we aimed to present venous involvement data in patients followed up with a diagnosis of BD.Methods:The clinical, demographic, laboratory and medication data of 394 patients who were followed up with a diagnosis of BD in our rheumatology outpatient clinic between 2000 and 2020 were retrospectively evaluated.Results:Venous involvement was detected in 17.6% (n:76) patients who were followed up with a diagnosis of BD. 75% of the patients were male, and their mean diagnosis age was 27.1±9.9, disease duration was 14.2±6.3 years. While the thrombosis of lower extremity veins, cervical veins, and vena cava were observed in 85.5% of BD patients, superficial thrombophlebitis was found in 31.6%. Cerebral venous involvement (CVI) was evaluated in cranial involvement. Oral aphthous ulcer was found in 97.4 % of the patients, genital ulcer in 65.8%, pathergy positivity in 44.7%, papulopustular lesion in 34.2%, erythema nodosum in 40.8%. 27.6% of the patients were evaluated for hereditary thrombophilia and 5.3% (n:7) had hereditary thrombophilia. Deep venous thrombosis was found in 85.7% (6/7) of these patients, renal artery occlusion in 14.3%, pulmonary artery thrombosis in 14.3%, and cerebral venous thrombosis in 28.6%. Patients with and without venous involvement were compared in terms of clinical findings. A significant difference was observed in terms of retinal vasculitis, artery occlusion, arterial aneurysm, family history for BD and gender. In logistic regression analysis, a significant relationship was observed between venous involvement and gender, family history, retinal vasculitis, artery occlusion, arterial aneurysm (Table1).Table 1.Comparison of data of patients with and without venous involvementVenous Involvement (+)n:76Venous Involvement (-) n:318POR* (%95CI)Gender0.0002.78(1.58-4.88) Female19(25)153(48.1) Male57(75)165(51.9)Family History4(5.3)44(13.8)0.0490.035(0.12-0.99)Oral Aphthous Ulcer74(97.4)305(95.9)0,745Genital Ulcer50(65.8)206(64.8)0,894Papulopustular lesion26(34.2)103(32.4)0,786Erythema Nodosum31(40.8)119(37.4)0,601Pathergy34(44.7)151(47.5)0,772Uveitis20(26.3)118(37.1)0,083Retinal Vasculitis5(6.6)6(1.9)0.0363.66(1.08-12.33)Arthritis13(17.1)85(26.7)0,104Artery Occlusion6(7.9)3(0.9)0.0028.97(2.19-36.74)Arterial Aneurysm7(9.2)8(2.5)0.0133.93(1.37-11.20)Gastrointestinal involvement6(7.9)11(3.5)0,111Cardiac involvement3(3.9)3(0.9)0,089Cranial involvement7(9.2)17(5.3)0,282* Significant data in logistic regression analysis were presentedConclusion:Superficial venous thrombosis and deep vein thrombosis are the most frequent vascular involvements in BD patients. Significant correlations exist between CVI and pulmonary artery involvement (PAI), intracardiac thrombosis and PAI. It should be recalled that lower extremity venous thrombosis is often present in these associations, and even precede them (1).References:[1]Seyahi E. Behçet’s disease: How to diagnose and treat vascular involvement. Best Practice & Research Clinical Rheumatology. 30 (2016) 279-295Disclosure of Interests:None declared

Hereditary gingival fibromatosis (HGF) is the most common genetic form of gingival fibromatosis that develops as a slowly progressive, benign, localized or generalized enlargement of keratinized gingiva. HGF is a genetically heterogeneous disorder and can be transmitted either as an autosomal-dominant or autosomal-recessive trait or appear sporadically. To date, four loci (2p22.1, 2p23.3–p22.3, 5q13–q22, and 11p15) have been mapped to autosomes and one gene ( SOS1 ) has been associated with the HGF trait observed to segregate in a dominant inheritance pattern. Here we report 11 individuals with HGF from three unrelated families. Whole-exome sequencing (WES) revealed three different truncating mutations including two frameshifts and one nonsense variant in RE1-silencing transcription factor ( REST ) in the probands from all families and further genetic and genomic analyses confirmed the WES-identified findings. REST is a transcriptional repressor that is expressed throughout the body; it has different roles in different cellular contexts, such as oncogenic and tumor-suppressor functions and hematopoietic and cardiac differentiation. Here we show the consequences of germline final-exon-truncating mutations in REST for organismal development and the association with the HGF phenotype.

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; ORGCA = 1.19, ORTAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA = 5.52E-04, ORGCA = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus., This work was supported by SAF2012– 34435 from the Spanish Ministry of Economy and Competitiveness, BIO-1395 from Junta de Andalucía, and RD12/0009/0004 from the RETICS Program (RIER) of Instituto de Salud Carlos III (ISCIII). FDC was recipient of a grant from the ‘Ramón y Cajal’ programme of the Spanish Ministry of Economy and Competitiveness (RYC-2014–16458). MCC and JHR are supported by Ministerio de Economía y Competitividad (SAF 14/57708R), cofunded by “Fondo Europeo de Desarrollo Regional, Unión Europea, Una manera de hacer Europa” [Instituto de Salud Carlos III and Fondo Europeo de desarrollo regional (FEDER) (PIE 13/00033)]. The Vasculitis Clinical Research Consortium has received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54AR057319), the National Center for Research Resources (U54 RR019497), the Office of Rare Diseases Research, and the National Center for Advancing Translational Science. The VCRC is part of the Rare Diseases Clinical Research Network (RDCRN).

Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a constellation of adult onset phenotypes consistent with an acceleration of intrinsic biological aging. It is caused by pathogenic variants in the WRN gene, which encodes a multifunctional nuclear protein with exonuclease and helicase activities. WRN protein is thought to be involved in optimization of various aspects of DNA metabolism, including DNA repair, recombination, replication, and transcription. In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations already reported in the literature. The Seattle International Registry recruits patients from all over the world to investigate genetic causes of a wide variety of progeroid syndromes in order to contribute to the knowledge of basic mechanisms of human aging. Given the unusually high prevalence of WS patients and heterozygous carriers in Japan, the major goal of the Japanese Consortium is to develop effective therapies and to establish management guidelines for WS patients in Japan and elsewhere. This review will also discuss potential translational approaches to this disorder, including those currently under investigation.

Objective: The aim of our study was to evaluate the changes of the melanocytic nevi during the biological agent therapy. Methods: For this purpose, 40 index nevi of 25 adult patients who were treated with infliximab, adalimumab, etanercept or rituximab were included in this study. All of the patients underwent clinical and dermoscopic evaluation before the beginning of the treatment, 6 months and 1 year after the beginning of the treatment. Among dermoscopic examination methods, pattern analysis, ABCD score system and three-point checklist were performed. Results: In terms of the diameter of the index nevi, there was no statistically significant difference between the first examination and that of the sixth month, but differences was observed between the first examination and that of the twelfth month. There was also no statistically significant difference in total dermoscopy scores calculated by ABCD score system application on 31 nevi at the times of assessment. At the end of the study, we detected 24 new nevi formation in 7 patients, whom all of were over 35 years of age, however no eruptive nevi or melanoma formation were observed. Conclusion: An increase in the diameters of the present nevi and formation of new nevi may be seen with biological agent therapy in one-year-follow-up.

Background:Rheumatoid arthritis(RA) is one of the most frequent rheumatic disease, and the age of onset is between 30-50 years old. Late-onset RA(LORA) is usually defined as RA with onset at age 60 or over.Objectives:To investigate the choice, effectiveness and the retention rate of biological drugs in LORA patients.Methods:TURKBIO registry is the Turkish version of Danish DANBIO rheumatological database which has been established in 2011. We studied RA patients in TURKBIO registry cohort between the dates of 2011 and 2020. All patients fulfilled the American College of Rheumatology criteria for RA and were classified into two groups based on their age at symptom onset: adult-onset RA(>18-Results:From 10 centers, 2111 RA patients recruited, and 8.8% of them was LORA patients. In LORA, the frequency of female was less than AORA. While, there was no difference between LORA and AORA in terms of erosion presence and RF positivity, antiCCP positivity was more frequent in LORA group. The use of antiTNF was lower, and the use of rituximab was more frequent in LORA. At 12 months after bDMARDs therapy, serum CRP and ESR levels and DAS28-CRP showed higher changes compared to baseline values in LORA. Although the mortality rate was higher in LORA, the adverse reactions were reported to be higher in AORA, and most common advers reaction was infections in both groups(Table). The longest survival was observed in infliximab and rituximab(median 22 and 20months) in LORA, in rituximab and golimumab(median 16 and 12months) in AORA.Conclusion:The frequency of LORA who uses bDMARDs was 8.8% in our database. In the elderly patient population, there are some reservations about the use of biological drugs in general due to several co-morbidities and concommitant drug used. Although data on this issue are limited, appropriate biological use can be effective and reliable in required patients.References:[1]Zulfigar AA, Niazi R, Pennaforte JL, Andres E. Late-onset rheumatoid arthritis: clinical, biyological, and therapeutic features about a retrospecttive study. Geriatr Psychol Neuropsychiatr Viell 2019;17:51-62Table.Comparison of demographic, laboratory findings and biological treatment(median;25-75)n(%)AORA ((n:1925)LORA (≥60)(n:186)pAge (year)54 (43-61)71 (68-74)Disease duration (year)11.4 (7-18)6 (4-9)Gender (Female)1562 (81)124 (67)Anti-CCP positivity747 (62)65 (72)0.044RF positivity721 (61)63 (70)0.085Erosion presence486 (56)41 (62)0.955Drug survival (months)18 (6-44)18 (4-31)0.046Concomitant csDMARDsMTX629 (34)39 (22)0.001SZP146 (8)13 (7)0.781LEF501 (27)35 (20)0.032bDMARDsAntiTNF1068 (56)73 (39)TCZ304 (16)20 (11)0,069TOFA294 (15)27 (15)0,784RTX439 (23)57 (31)0,016ABA298 (16)34 (18)0,317Response ΔESH-6 (-21-4)-18 (-36--3)0.016(12 months) ΔCRP-2 (-12-0.6)-9.3 (-28--0.1)0.014ΔDAS28-CRP-1.3 (-3--0.1)-2.2 (-3--1)0.023ΔHAQ-0.3 (-0.8-0)-0.4 (-0.8--0.1)0.114Adverse effects440 (23)32 (17)0.077Malignancy9 (0,5)3 (1.6)0.082Infection192 (10)10 (5)0.042Allergy63 (3)4 (2)0.404Dermatitis62 (3)1 (0,5)0.040Death18 (0.9)7 (4)0.004Other136 (7)11 (6)0.556Acknowledgments :NoneDisclosure of Interests: :None declared