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The immune system plays a crucial role in the response against severe acute respiratory syndrome coronavirus 2 with significant differences among patients. The study investigated the relationships between lymphocyte subsets, cytokines, and disease outcomes in patients with coronavirus disease 2019 (COVID‐19). The measurements of peripheral blood lymphocytes subsets and cytokine levels were performed by flow cytometry for 57 COVID‐19 patients. Patients were categorized into two groups according to the severity of the disease (nonsevere vs. severe). Total lymphocytes, T cells, CD4+ T cells, CD8+ T cells, B cells, and natural killer cells were decreased in COVID‐19 patients and statistical differences were found among different severity of illness and survival states (P ˂ 0.01). The levels of IL‐6 and IL‐10 were significantly higher in severe and death groups and negatively correlated with lymphocyte subsets counts. The percentages of Th17 in the peripheral blood of patients were higher than those of healthy controls whereas the percentages of Th2 were lower. For the severe cases, the area under receiver operating characteristic (ROC) curve of IL‐6 was the largest among all the immune parameters (0.964; 95% confidence interval: 0.927–1.000, P 106.44 pg/ml and CD8+ T cell counts, Graphical Abstract COVID‐19 patients with poor prognosis exhibited a significant depletion of lymphocyte‐subset counts, with remarkably increasing concentrations of IL6 and IL10.

Introduction: Inborn errors of immunity (IEI) represent a heterogeneous large group of genetic disorders characterized by susceptibility of affected individuals to recurrent infections, autoimmune/inflammatory diseases, allergies and malignancy. We aim to report for the first time the Algerian registry for IEI in children.Methods: We describe the characteristics of IEI in Algerian children from the data collected in the Algerian registry for IEI over a long period of 37 years.Results: Between 1985 and 2021, we included 887 children (530 male, 59.6%) with a mean age at diagnosis of 3.23y and a mean diagnosis delay of 2y. The prevalence rate was estimated at 1.97/100,000 inhabitants or 5.91/100,000 children. The parental consanguinity was found in 52.6%. The most prevalent category was combined immunodeficiencies (CID) (35.5%) followed by predominantly antibody deficiencies (24.4%) and CID with syndromic features (17.9%). The most predominant diseases were severe CID (120 cases), MHC II deficiency (99 cases), agammaglobulinemia (81 cases), common variable immunodeficiency (74 cases), hyper IgE syndromes (60 patients), ataxia telangiectasia (46 patients), Wiskott Aldrich syndrome (40 patients) and chronic granulomatous disease (39 cases). The clinical presentation was dominated by lower respiratory tract infections (69%), failure to thrive (38.3%) and chronic diarrhea (35.2%). Genetic analysis was performed in 156 patients (17.6%). The global mortality rate was 28.4% mainly caused by CID.Conclusion: This is the first report of the Algerian registry for IEI in children. Data is globally similar to that of Middle East and North African (MENA) registries with high consanguinity, predominance of CID, and significant mortality. This registry highlights the weak points that should be improved in order to provide better patient care.

Background Plasma cell dyscrasias (PCD) are a heterogeneous group of diseases characterized by the expansion of monoclonal bone marrow plasma cells that produce a monoclonal immunoglobulin (M-component). Purpose This is a retrospective study that describes the epidemiological, immunochemical features and etiology of monoclonal gammopathies diagnosed between 1998 and 2016 in the Teaching Hospital Beni-Messous of Algiers. Patients and methods 2121 cases of monoclonal gammopathies (MG) were collected during this period. Serum/urine protein electrophoresis, serum/urine immunofixation and serum free light chain measurements were used to demonstrate M protein. Results The middle age of the patients at the time of the diagnosis were 62.96 ± 13.19 years with extremes ranging from 07 to 99 years. The study included 1013 (47, 76 %) men and 1108 (52, 23 %) women with a sex ratio 0,91. Isotypes repartition was: IgG (60.91 %), IgA (17.91 %), light chain (10.46 %), IgM (6.6 %), IgD (1.03 %) and IgE (0.09 %) of cases. The most frequent diagnosis was: Multiple Myeloma (55.20 %), followed by monoclonal gammopathy of undetermined significance (34.13 %). Conclusion In our study, two particularities were noted. There is no male predominance in Algerian PCD patients. Moreover, we observed a higher frequency of light chain multiple myeloma and lower frequency of IgM isotype compared to western studies.

Human inborn errors of immunity (IEI) are a group of 485 distinct genetic disorders affecting children and adults. Signs and symptoms of IEI are heterogeneous, and accurate diagnosis can be challenging and depends on the available human expertise and laboratory resources. The Middle East and North Africa (MENA) region has an increased prevalence of IEI because of the high rate of consanguinity with a predominance of autosomal recessive disorders. This area also exhibits more severe disease phenotypes compared with other regions, probably due to the delay in diagnosis. The MENA-IEI registry network has designed protocols and guidelines for the diagnosis and treatment of IEI, taking into consideration the variable regional expertise and resources. These guidelines are primarily meant to improve the care of patients within the region, but can also be followed in other regions with similar patient populations.

Monogenic immune dysregulation diseases (MIDD) are caused by defective immunotolerance. This study was designed to increase knowledge on the prevalence and spectrum of MIDDs, genetic patterns, and outcomes in Middle East and North Africa (MENA). MIDD patients from 11 MENA countries (Iran, Turkey, Kuwait, Oman, Algeria, Egypt, United Arab Emirates, Tunisia, Jordan, Qatar, and Azerbaijan) were retrospectively evaluated. 343 MIDD patients (58% males and 42% female) at a median (IQR) age of 101 (42-192) months were enrolled. The most common defective genes were LRBA (23.9%), LYST (8.2%), and RAB27A (7.9%). The most prevalent initial and overall manifestations were infections (32.2% and 75.1%), autoimmunity (18.6% and 41%), and organomegaly (13.3% and 53.8%), respectively. Treatments included immunoglobulin replacement therapy (53%), hematopoietic stem cell transplantation (HSCT) (14.3%), immunosuppressives (36.7%), and surgery (3.5%). Twenty-nine (59.2%) patients survived HSCT. Along with infectious complications, autoimmunity and organomegaly may be the initial or predominant manifestations of MIDD., Alborz University of Medical Sciences, This work was supported by the vice chancellor for research, Alborz University of Medical Sciences.

Resume L’immunotherapie orale (ITO) a ete reconnue comme un traitement prometteur pour l’allergie aux proteines de lait de vache (APLV) persistante. L’objectif de cette etude est d’analyser les caracteristiques cliniques, biologiques et evolutives des malades sous ITO. Methodes Etude prospective realisee au niveau du service de pediatrie A au CHU Beni Messous a Alger, ayant concerne tous les enfants suivis pour APLV et chez lesquels une ITO a ete pratiquee. Resultats Cent vingt-huit malades sont suivis pour APLV IgE mediee dont 38 ont necessite une ITO (22,8 %), 24 garcons et 14 filles, l’âge median a l’ITO 4,8 ans (1,5–10,5), la dose initiale etait comprise entre 0,6 et 100 ml, le lait cuit etait utilise chez tous les malades dont 52,6 % cuit dans une matrice de ble. La duree moyenne de l’ITO etait 17,5 mois avec une moyenne d’âge de guerison de 6,5 ans. Un taux eleve des IgE specifiques au lait de vache et particulierement a la caseine etait correle a un âge de guerison plus avance. 55,2 % ont un asthme associe. Des reactions allergiques legeres a moderees ont ete rapportees sans recours a l’adrenaline sauf chez un seul malade. Conclusion Les resultats sont encourageants, 63 % consomment plus de 200 ml/j de lait, les autres sont en escalade therapeutique personnalisee. La cinetique des IgE specifiques et des tests cutanes ont permis de guider l’ITO. Bien que les incidents fussent peu frequents, la vigilance s’impose au cours de l’ITO.

Background Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis. Methods We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers. Results We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG). Conclusions This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation., Karolinska Institute, Open access funding provided by Karolinska Institute.

Background Interferon regulatory factor 5 (IRF5) is a transcription factor regulating interferon secretion and was proved to be implicated in the pathogenesis of systemic lupus erythematosus (SLE) in several studies. The purpose of this case-control study was to investigate whether IRF5 gene polymorphism is involved in the genetic predisposition to SLE in the Algerian population. Methods IRF5 rs729302 (A/C) polymorphism was analyzed in 120 SLE patients and 98 age and sex matched controls by real time- polymerase chain reaction. Results Significant association was observed for AA and AC genotypes of IRF5 between patients and healthy subjects (60% vs 73%; 40% vs 27%, p =0.025, respectively). Patients with SLE had more frequent C allele compared to controls (20% vs 13%, P = 0.041). However, the allele and genotype frequencies did not show any difference in patients with nephritis in comparison to those without nephritis. Conclusion The rs729302 C allele and AC genotype can be considered as risk factors for the development of SLE in Algerian patients.

Accumulating evidence supports that the viral-induced hyper-inflammatory immune response plays a central role in COVID-19 pathogenesis. It might be involved in the progression to acute respiratory distress syndrome (ARDS), multi-organ failure leading to death. In this study, we aimed to evaluate the prognostic value of the immune-inflammatory biomarkers in COVID-19, then determine optimal thresholds for assessing severe and fatal forms of this disease.153 patients with confirmed COVID-19 were included in this study, and classified into non-severe and severe groups. Plasmatic levels of interleukin 6 (IL6), C-reactive protein (CRP), soluble-IL2 receptor (IL2Rα), procalcitonin (PCT) and ferritin were measured using chemiluminescence assay. Complete blood count was performed by Convergys 3X® hematology analyzer. Our results demonstrated that the peripheral blood levels of IL6, PCT, CRP, ferritin, IL2Rα, white blood cell count (WBC), neutrophil count (NEU), neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR) were significantly higher in severe forms of COVID-19. The ROC curve analysis showed that IL6 was the most accurate inflammatory biomarker. The calculated cutoff of IL6 (42 pg/ml) could correctly classify > 90% of patients regarding their risk of severity (area under ROC curve (AUROC) = 0.972) and the threshold value of 83 pg/ml was highly predictive of the progression to death (AUROC = 0.94, OR = 184) after a median of 3 days. Besides, IL-6 was positively correlated with other inflammatory markers and the kinetic analysis highlighted its value for monitoring COVID-19 patients. PCT and NLR had also a high prognostic relevance to assess severe forms of COVID-19 with corresponding AUROC of 0.856, 0.831 respectively. Furthermore the cut-off values of PCT (0.16 ng/ml) and NLR (7.4) allowed to predict mortality with high accuracy (se = 96.3%, sp = 70.5%,OR = 61.2)’ (se = 75%, sp = 84%, OR = 14.6).The levels of these parameters were not influenced by corticosteroid treatment, which make them potential prognostic markers when patients are already undergoing steroid therapy.

Increasing evidence suggests that the rs6822844, within KIAA1109/TENR/IL2/IL21 gene cluster on 4q27, is strongly associated with rheumatoid arthritis (RA) in the Caucasian population. The aim of this study is to investigate the possible association between the SNP rs6822844 and susceptibility to RA in the Algerian Maghreb population, and to explore the association with the clinical and immunological features of RA. The polymorphism rs6822844 was genotyped in 323 RA patients and 323 healthy individuals using the TaqMan assay. A strong association of IL2/IL21 with RA susceptibility was detected in the Algerian population [odds ratio (OR) = 2.57 (95% confidence interval (CI) 1.74-3.83), P = 10(-4) ]. Our results revealed that IL2/IL21 predisposed to disease development in both autoantibody positive and negative disease. Meanwhile, the association was stronger in RA patients with anti-cyclic citrullinated peptides (ACPA) positive than those with ACPA negative [OR = 2.30 (95% CI 1.53-3.51), P = 10(-4) and OR = 1.98 (95% CI 1.01-4.22), P = 0.037, respectively]. Moreover, our findings showed a moderate association of the rs6822844 polymorphism with disease activity (P = 0.014). This study indicates for the first time that there is a strong association between IL2/IL21 rs6822844 variant and susceptibility to RA in the Algerian population, and that this association was independent from the autoantibodies status of RA patients.

This study aimed to evaluate the effects of estrogen reduction on amyloid deposition, some lipid metabolism and oxidative stress markers, PSA-like production and p63 expression in the prostate of the adult rat.Aromatase inhibitor: Formestane (4-OHA), was administrated to male rats, at a dose of 0.1 mg/kg b.w./day, for 10 days. The control group (CONT) received the same volume of placebo injection (NaCl 0.9%).4-OHA treatment induced a significant accumulation of intraprostatic cholesterol (138.90 ± 17.64 vs 85.12 ± 2.87, p = 0.01); against an insignificant diminution of malondialdehyde (412.6 ± 54.35 vs 842.70 ± 336.50, p 0.05) and glutathione (2.40 ± 0.23 vs 3.65 ± 0.88, p 0.05). This was associated with a significant decrease of nitric oxide (31.76 ± 7.07 vs 179.40 ± 58.35, p = 0.024). Additionally, 4-OHA significantly increased the intraprostatic production of PSA-like (11.12 ± 2.78 vs 3.91 ± 0.43, p = 0.043). The prostatic histology revealed an amyloid deposition, in all prostatic lobes and a smooth muscle layer growth (p 0.05); especially significant in the dorsal and lateral lobes. Theses lobes manifested a basal cells proliferation, with a 3-fold increase of p63 expression (p 0.001). The ventral lobe presented epithelial atrophy (37.80 ± 16.20 vs 167.60 ± 5.16, p 0.05); with occasional and significant proliferative foci (247.00 ± 9.573 vs 167.60 ± 5.16 p 0.05).Aromatase inhibition, in the adult male rat, alters the prostatic function by reducing nitric oxide availability and inducing amyloid deposition along with limiting the differentiation of basal cells, through a lobe-specific p63-overexpression.

Background Vitamin D (VD) is a steroid hormone belonging to the class of secosteroids with myriad immune functions and seems to be involved in the development and severity of rheumatoid arthritis (RA).1–3 Objectives The aim of this study was to estimate the prevalence of vitamin D deficiency in patients with rheumatoid arthritis as compared to healthy controls and to analyse the association between levels of vitamin D and CRP(C-reactive protein)/ACPA (anti citrullinated protein antibodies) positivity. Methods Serum 25(OH)D levels were measured in 115 RA patients and 104 age- and gender-matched healthy controls using the chemiluminescent immunoassay method (CLIA). CRP (mg/dl) was measured by the nephelometric method and ACPA antibodies were evaluated using enzymatic linked immuno-assay (ELISA). Results There was no statistically significant difference between levels of 25(OH)D in RA (25.08±9.22 ng/ml) and healthy controls (15.62±5.34 ng/ml). The vitamin D deficiency ( Low 25-OHD levels were negatively associated with CRP (23 ng/ml vs 29 ng/ml; p=0,023) and ACPA positivity (23 ng/ml vs 28 ng/ml; p=0, 03). Conclusions The 25(OH) D levels are inversely related to CRP and ACPA values in Algerian RA patients. References [1] Lee YH, Bae SC. Vitamin D level in rheumatoid arthritis and its correlation with the disease activity: a meta-analysis. Clin Exp Rheumatol. 2016Sep–Oct;34(5):827–833. [2] Bragazzi NL, Watad A, Neumann SG, et al.Vitamin D and rheumatoid arthritis: an ongoing mystery. Curr Opin Rheumatol2017Jul;29(4):378–388. [3] Ishikawa LLW, Colavite PM, Fraga-Silva TFC, et al. Vitamin D Deficiency and Rheumatoid Arthritis. Clin Rev Allergy Immunol2017Jun;52(3):373–388. Disclosure of Interest None declared

Multiple myeloma is characterized by underlying clinical and biological heterogeneity, which translates to variable responses to treatment and outcome.To assess the roles of serum free light chain (sFLC) and K/L FLC ratio (rFLC) in the diagnoses and prognoses of multiple myeloma (MM), sFLC levels and K/L ratios were measured in 112 patients with newly diagnosed multiple myeloma using the Freelite automated immunoassay.Abnormal sFLC and/or rFLC levels were detected 99.1% of the patients. The baseline sFLC predicted the overall survival (OS). The median OSs were not reached (NR) and were 30 months in the low sFLC group (sFLC-K132 mg/L or sFLC-L342 mg/L) and the high sFLC group (sFLC-K ≥ 132 mg/L or sFLC-L ≥ 342 mg/ L) (p0.001), respectively. Similarly, the rFLC successfully predicted the OS times of 29 months for group A (rFLC ≤ 0.03 or ≥ 32) and NR for group B (0.03rFLC32) (p0.001). According to the response to treatment and sFLC ratio, significant differences in the OSs were observed between the partial response group and other patients, (respectively, OS median = 28 months vs. NR, log rank p0.001). Additionally, the patients were further stratified into two groups using the novel poor-prognosis factors (rFLC32 or0.03) combined with the International Staging System parameters (beta2-microglobulin, albumin), i.e., a low-risk group (those with zero or one factor) and a high-risk group (those with two or three factors). The median OSs for the low- and high-risk groups were NR and 29 months, respectively (p = 0.001).The sFLC assay was extremely sensitive in the diagnosis of MM. In addition to its strong prognosis value, it could be a predictor of response to therapy.

Background: The aims of this study were to establish the clinical value of multi-parametric flow cytomentry (MFC) in multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). Methods: We analyzed bone marrow aspirates from 112 MM and 17 MGUS patients by MFC, using 3 combinations of 9 color labeling: a, CD38 / CD138 / CD45 / CD56 / CD19 / CD27 / CD117 / CD20 / CD33; b, CD38 / CD138 / CD45 / cytoplasmic Kappa / cytoplasmic Lambda; and c, CD38 / CD138. MFC data were classified based on clinical features and prognosis factors. Results: Myeloma’s patients compared to MGUS group had plasma cells (PCs) with abnormal immunophenotypic patterns, including high CD56 and CD20 expression and weak or negative CD45, CD19, and CD27 expression without significant median differences in expression of CD33 and CD117. Multiple myeloma patient with low expression of CD19, CD27 or CD45, overexpression of CD56 or with a high proportion of PCs at diagnosis demonstrated shorter overall survival times. Moreover, MM patients with combined abnormal expressions of 4 or 5 antigens demonstrated shorter survival times (P = 0.001). These high-risk MFC patients were associated with poor clinical outcomes, including ISS stage III and DS stage III, low hemoglobin levels, and elevated serum beta2-microglobilin (P = 0.01, P = 0.006, P = 0.01 and P = 0.008, respectively). Conclusions: The present study highlights the benefits of assessing abnormal antigen expression for clinical uses. These measures could facilitate proper diagnosis of disorders and improve risk stratification for a targeted early treatment regimen.

IgD multiple myeloma (MM) is a rare subtype of myeloma, it affects less than 2% of patients with MM. To evaluate the clinical and prognostic attributes of serum free light chains (sFLCs) analysis, we examined 17 cases of IgD MM. From 1998 to 2012, we obtained 1250 monoclonal gammapathies including 590 multiple myeloma and 17 patients had IgD MM. With preponderance of men patients with a mean age at diagnosis of: 59±12years. Patients with IgD MM have a short survival (Median survival=9months). The presenting features included: bone pain (75%), lymphadenopathy (16%), hepatomegaly (25%), splenomegaly (8%), associated AL amyloidosis (6%), renal impairment function (82%), infections (47%), hypercalcemia (37%) and anemia (93%). Serum electrophoresis showed a subtle M-spike (Mean=13.22±10g/L) in all patients associated to a hypogammaglobulinemia. There was an over-representation of Lambda light chain (65%); high serum β2-microglobulin in 91% and Bence Jones proteinuria was identified in 71%. The median rate of sFLCs κ was 19.05mg/L and 296.75mg/L for sFLCs λ. sFLCR was abnormal in 93% of patients and it showed concordance between baseline sFLCR and the survival (P=0.034). The contribution of FLC assay is crucial for the prognosis of patients with IgD MM.

Resume Propos Le deficit immunitaire commun variable (DICV) est le plus frequent des deficits immunitaires symptomatiques. Il est caracterise par un defaut de production d’anticorps, des infections a repetition le plus souvent des voies aeriennes et une survenue accrue des affections auto-immunes et lymphoproliferatives. Methodes Il s’agit d’une etude retrospective portant sur 29 patients atteints de DICV. Un dosage ponderal des immunoglobulines et une analyse des sous-populations lymphocytaires ont ete realises chez nos patients. Resultats Vingt-neuf cas ont ete analyses. L’âge moyen au moment du diagnostic etait de 23 ans. Des infections a repetition, principalement des pneumopathies et des infections ORL, ont ete decrites quasiment chez tous les patients. Les manifestations auto-immunes et lymphoproliferatives ont ete retrouvees chez 5 et 6 patients respectivement. Une diminution d’IgG etait retrouvee quasiment chez tous les patients, elle etait associee a une diminution d’IgA et d’IgM dans 89,7 % et 65,5 % des cas respectivement. Trois quarts (75 %) de nos patients ont un phenotype T et/ou B perturbe. On retrouve en particulier des lymphopenies B (54,2 %) et T CD4+ (41,7 %) et une inversion du rapport CD4/CD8 (70,8 %). La survenue d’une splenomegalie et/ou d’une cytopenie auto-immune est associee a un taux significativement plus bas en lymphocytes B et T CD4+ circulants. Conclusions Notre travail illustre l’extreme heterogeneite du DICV tant sur le plan clinique que sur le plan immunologique. La classification des patients atteints de cette maladie est essentielle pour permettre de definir des groupes homogenes et de caracteriser les anomalies moleculaires propres a chaque groupe.

Methotrexate (MTX) is the most used drug in rheumatoid arthritis (RA) treatment. However, it shows variability in clinical response, which is explained by an association with genetic polymorphisms. This study aimed to elucidate the role of the two gene polymorphism C677T and A1298C of the methylenetetrahydrofolate reductase (MTHFR) in response to MTX in Algerian RA patients. Study included 54 early RA patient treated with MTX for one year. MTX efficiency and toxicity were evaluated at 6 and 12 months respectively and the two gene polymorphisms were genotyped. No association was found between A1298C polymorphism and MTX toxicity. However, T allele of the C677T polymorphism was associated with the occurrence of MTX adverse effects (p = 0,019, OR: 3,63, 95% CI [1,12 - 12,80]). No association was found between C677T polymorphism and MTX efficiency, while A allele of the A1298C polymorphism was associated with good and moderate response (p = 0,02, OR = 3,28, 95% CI: [1,11– 9,42]). The study of RA biological markers kinetics showed that MTX did not affect antibodies rate unlike inflammatory markers. Our study suggests that MTHFR C677T and A1298C genotyping are associated to MTX toxicity and efficiency, respectively, in RA patients. This offers new perspectives in the personalization of RA treatment in Algeria.

Introduction Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory and multifactorial disease. Genetic predisposition seems to play an important role. The aim of this study is to explore the relationship between human leukocyte antigen (HLA)-DRB1 alleles and susceptibility, clinical and biological features of RA in an Algerian patient population. Methods Using polymerase chain reaction – sequence specific primers (SSP), 134 RA patients and 132 healthy controls were genotyped for HLA-DRB1 and HLA-DRB1*04 subtypes. Results HLA-DRB1*04 was found to have increased frequency in the RA group compared to controls (P

Resume But de l’etude Parmi les cytokines pro-inflammatoires qui jouent un role important dans la physiopathologie de la polyarthrite rhumatoide (PR), l’interleukine 1 (IL-1). Le but de cette etude est d’evaluer la relation entre les polymorphismes de l’IL-1B en position -511 et +3953, du recepteur antagoniste de l’IL-1 (IL1-RN VNTR) et la survenue de la PR dans une population algerienne ainsi que leurs correlations avec les differents phenotypes clinico-biologiques. Patients et methodes Cent quarante-sept patients diagnostiques PR (119 femmes, 28 hommes) et 127 sujets temoins (70 femmes, 57 hommes) etaient inclus dans l’etude. L’analyse des deux polymorphismes IL-1B-511 et IL-1B+3953 etait faite par PCR-RFLP et l’analyse du polymorphisme IL1-RN VNTR etait realisee par PCR. Resultats Aucune difference significative n’a ete notee dans les frequences genotypiques, alleliques et haplotypiques des trois polymorphismes etudies entre les patients atteints de PR et les temoins. Cependant, le genotype (T/T) du polymorphisme de l’IL-1B-511 est plus frequents chez le groupe de patients PR avec ACPA positifs comparativement au groupe PR ACPA negatifs ( p c = 0,01 ; OR = 4,65). On a note egalement chez ce meme groupe de patients que l’haplotype (IL-1RN*1/IL-1B-511 T/IL-1B+3953C) etait plus frequent ( p c = 0,03 ; OR = 2,05). Conclusion La combinaison formee de l’allele 1 du polymorphisme IL1-RN VNTR et l’allele T du polymorphisme IL1B-511 et l’allele C du polymorphisme IL1-B +3953 semble predisposer a la synthese d’ACPA et par consequent a la survenue de PR/ACPA (+). Des etudes complementaires sur un nombre de patients plus importants sont necessaires pour conclure du role de l’IL-1 dans la susceptibilite et/ou severite de la PR.

Objective: Previous studies implicated that IL17/IL23 pathway and TH17 cells play an important role in autoimmune inflammation. Genome wide association studies have identified multiple single nucleotide polymorphisms (SNPs) in the IL23R and IL17 genes region associated with rheumatoid arthritis (RA). Methods: In this study, we investigated the association of IL23R, IL17A and IL17F genes SNPs with RA susceptibility in the Algerian population. 343 patients with RA and 323 healthy subjects were genotyped for IL23R (rs11209026, rs1343151, rs10489629), IL17F (rs763780, rs2397084) and IL17A (rs2275913) variants by TaqMan technology. Results: There was no evidence of a genetic association between IL23R, IL17F and IL17A SNPs and RA susceptibility in our population. However, IL23R rs1343151 variant enhanced the development of RF IgM and IgG positive (+) RA as compared with RF IgM and IgG negative (-) RA (OR 2.29, p = 0.004 and OR 0.64, p = 0.014 respectively). Also, IL23R rs10489629 was associated with all RF isotypes positive disease (IgM+: OR 2.16, p = 0,006; IgG+: OR 0.64, p = 0,004 and IgA+: OR 1.54, p = 0,013). A moderate association of IL17A rs2275913 with RF IgA- RA subgroup was shown (OR 1.95, p = 0,039). Moreover, our data showed a correlation between IL23R and IL17F variants and the parameters of disease activity such as HAQ score and disease duration. Conclusion: The current study emphasizes the lack of association of IL23R and IL17 polymorphisms with RA susceptibility in the Algerian population. However, the data showed the relationship between IL23R and IL17A polymorphisms and the production of the different RF isotypes in RA patients.

International audience; X linked agammaglobulinemia (XLA) is the first described primary immunodeficiency and the most common form of agammaglobulinemia. It is characterized by susceptibility to recurrent infections, profound decrease of all immunoglobulin isotypes and very low level of B lymphocytes in peripheral blood. The disorder is caused by mutations in the Bruton's Tyrosine Kinase (BTK). Nine male patients suspected to have XLA from nine unrelated families were enrolled in this study. We performed sequencing of the BTK gene in all nine patients, and in the patients' relatives when possible. The XLA diagnosis was confirmed for six patients with six different mutations; we identified a novel mutation (c.1522GN A) and five known mutations. One third of nine unrelated patients do not have mutations in BTK and thus likely suffer from autosomal recessive agammaglobulinemia in the setting of consanguinity. Our results support that the autosomal recessive agammaglobulinemia can be more common in Algeria.

This study is the first to report epidermodysplasia verruciformis (EV) associated with ARTEMIS deficiency in a young adult. This broadens the clinical scope of ARTEMIS deficiency, and provides a new genetic etiology for susceptibility to EV.

Presenting processed antigens to CD4+ lymphocytes during the immune response involves major histocompatibility complex class II molecules. MHC class II genes transcription is regulated by four transcription factors: CIITA, RFXANK, RFX5 and RFXAP. Defects in these factors result in major histocompatibility complex class II expression deficiency, a primary combined immunodeficiency frequent in North Africa. Autosomal recessive mutations in the RFXANK gene have been reported as being the principal defect found in North African patients with this disorder. In this paper, we describe clinical, immunological and genetic features of 11 unrelated Algerian patients whose monocytes display a total absence of MHC class II molecules. They shared mainly the same clinical picture which included protracted diarrhoea and respiratory tract recurrent infections. Genetic analysis revealed that 9 of the 11 patients had the same RFXANK founder mutation, a 26 bp deletion (named I5E6-25_I5E6+1, also known as 752delG26). Immunological and genetic findings in our series may facilitate genetic counselling implementation for Algerian consanguineous families. Further studies need to be conducted to determine 752delG26 heterozygous mutation frequency in Algerian population.

Joint Bone Spine - In Press.Proof corrected by the author Available online since vendredi 1 mars 2013

Revue du rhumatisme - In Press.Proof corrected by the author Available online since mardi 7 mai 2013

Background Increasing evidence suggest that single nucleotide polymorphism (SNP) rs6822844 , within KIAA1109-TENR-IL2-IL21 gene cluster, is strongly associated with autoimmune diseases in Caucasian population, including rheumatoid arthritis (RA) [1, 2, 3]. Objectives The aim of this study was to investigate possible association between this polymorphism, susceptibility to RA, auto-antibody profile and RA severity in Algerian population. Methods We investigated 289 Algerian patients with RA and 266 healthy subjects, for rs6822844 polymorphism, using Taqman allelic discrimination assays (Applied biosystems 7500). We recorded demographics, clinical, and laboratory data, including evidence of inflammatory activity and presence of autoantibodies (rheumatoid factor (RF) and cyclic citrullinated peptide antibodies (anti-CCP)). Results The allele G of IL-21 gene polymorphism ( rs6822844 ) was associated significantly with susceptibility to RA (odds ratio (OR) =1.33 [95% CI 1.21 to 1.46], p =0.000). No significant association was observed between rs6822844 and ACPA+ or ACPA- RA groups. However, the major G allele frequency was significantly increased in the RF- RA group compared with RF+ RA group (96% vs 92%, OR=0.95 [95% CI 0.91 to 0.99], p =0.039). Concerning RA severity, the minor T allele was associated with (1) disease activity, assessed by HAQ score and DAS-28-CRP, and (2) ACPA serum levels ( p =0.027, p =0.031 and p =0.005 respectively). Conclusions Our results indicate that there is a strong relationship between rs6822844, susceptibility and severity of RA in Algerian population. References Amit K. Maiti, Xana Kim-Howard, Parvathi Viswanathan, Laura Guillen, Adriana Rojas- Villarraga, Harshal Deshmukh, Haner Direskeneli, Guher Saruhan-Direskeneli, Carlos Canas, Gabriel J. Tobόn, Amr H. Sawalha, Alejandra C. Chernavsky, Juan-Manuel Anaya, Swapan K. Confirmation of an Association Between rs6822844 at the IL2–IL21 Region and Multiple Autoimmune Diseases: Evidence of a General Susceptibility Locus. Arthritis & rheumatism 2010; 62: 323–329. Hollis-Moffatt JE, Chen-Xu M, Topless R, Dalbeth N, Gow PJ, Harrison AA, Highton J, Jones PB, Nissen M, Smith MD, van Rij A, Jones GT, Stamp LK, Merriman TR. Only one independent genetic association with rheumatoid arthritis within the KIAA1109-TENR-IL2-IL21 locus in Caucasian sample sets: confirmation of association of rs6822844 with rheumatoid arthritis at a genome-wide level of significance. Arthritis Research & Therapy 2010; 12: R116. Nina A. Daha, Fina A. S. Kurreeman, Rute B. Marques, Gerrie Stoeken-Rijsbergen, Willem Verduijn, Tom W. J. Huizinga, Rene E. M. Toes. Confirmation of STAT4, IL2/IL21, and CTLA4 Polymorphisms in Rheumatoid Arthritis. Arthritis & rheumatism 2009; 60: 1255–1260. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1950

Background The B-cell lymphocyte kinase (BLK) is a src family protein tyrosine kinase expressed in B-lineage cells. BLK gene polymorphism was reported as a risk factor in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) susceptibility. Objectives To investigate whether the association of BLK gene polymorphism with RA is present in an Algerian population. Methods The BLK (rs13277113) single nucleotide polymorphism was directly genotyped in 223 RA patients and 200 healthy controls by real time -polymerase chain reaction method (TaqMan Assays). The relationships between anti-citrullinated peptide antibody (ACPA) positivity, rheumatoid factor (RF) positivity and BLK genotypes were analyzed statistically. Disease activity score (DAS28) and HAQ score were also assessed. Results Significant associations between RA and controls were observed for AG heterozygote genotype (21% vs 33%, P=0.004, OR=0.53) and recessive model (AA vs. AG+GG, 94% vs 99%, P=0.002, OR=0.08). Allele frequencies did not differ between patients and controls and between antibodies positive (ACPA, RF) and negative RA (P>0.05). No significant difference in genotypes distribution was found after stratification according to parameters of disease activity (DAS 28 and HAQ, P>0.05). Conclusions Our result indicates that polymorphism in BLK gene is associated with susceptibility to RA in Algerian population but not with the severity. References Genin E, Coustet B, Allanore Y, et al. Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis. PLoS One. 2013 Apr 30;8(4) Viatte S, Plant D, Bowes J, et al. Genetic markers of rheumatoid arthritis susceptibility in anti-citrullinated peptide antibody negative patients. Ann Rheum Dis. 2012 Dec;71(12) Zhang H, Wang L, Huang Y, et al. Influence of BLK polymorphisms on the risk of rheumatoid arthritis. Mol Biol Rep. 2012 Nov;39(11). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1943

Background Articular manifestations are common in systemic sclerosis (SSc), and joint pain is a frequent presenting feature of this disease. Joint symptoms have been noted in 12 to 66% of patients at the time of diagnosis and in 24 to 97% of patients at some time during the course of their illness. Objectives To determine frequency and features of erosive and non erosive arthritis in a prospective study of systemic sclerosis patients Methods One hundred fifty (150) patients attending the rheumatology department at Ben Aknoun Hospital, as part of a prospective study and fulfilling the ACR and/or Leroy and Medsger criteria for systemic sclerosis were evaluated by one author. Joint involvement was classified as follows: arthralgias, arthritis (joint swelling and tenderness on physical examination or synovitis on US), erosive arthritis (erosions and joint space narrowing on radiographs or erosions on US). Only wrists, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints were studied. Standard radiographs of the hands and wrists were obtained and evaluated. All radiographs were evaluated without knowledge of the clinical or serological data of the patients examined. The presence of either extra-articular (subcutaneous calcinosis and digital tuft resorption) or articular involvement (juxta-articular osteoporosis, marginal erosions and joint space narrowing) was recorded. Ultrasonography (US) of the wrists, the MCP and the PIP was performed in patients without arthritis on joint examination or with normal radiographs. All autoantibody analyses were performed in the Laboratory of Beni Messous hospital, Algiers, Algeria. The statistical significance for the various associations was calculated using the X 2 test. The difference was significant when p value Results 139 women and 11 men with a median age of 45.12±13.59 years and a disease duration (first non-Raynaud symptom) of 9.7 years. 42 patients had a diffuse scleroderma, 108 patients had a limited scleroderma. 60 patients had arthritis. Arthritis were inaugural in 41.7%. There was no significant difference between patients with or without arthritis in term of digital ulcers, skin, lung, heart and kidney involvement. Anti-CCP2 was positive in 16.5% patients with arthritis and in 4.5% patients without arthritis (p=0.01) 21 patients had erosive arthritis, An overlap with Rheumatoid Arthritis (RA) was found in only 7 patients. Patients with erosive arthritis had more diffuse cutaneous involvement (42.9%) (p=0.01), digital ulcers (81%) (p = 0.009) and ILD (81%) (p=0.009). Anti-CCP2 was positive in 33.3 % patients with erosive arthritis and in 7.7 % patients without erosive arthritis (p = 0.01). Anti-topoisomerase 1 antibody was positive in 71.4 % patients with erosive arthritis and in 38.5 % patients without erosive arthritis (p = 0.01). We also compared patients with erosive arthritis, with and without overlap syndrome (SSc-RA) 14 patients had erosive arthritis but no RA. Those patients had more flexion contracture (92.9%) (p=0.01), digital ulcers (92.9%) (p=0.04), acro-osteolysis (50%) (p=0.04), esophagus involvement (100%) (p=0.03) and ILD (92.9%) (p=0.04). Conclusions Erosive arthritis and particularly systemic sclerosis erosive arthropathy was associated with a severe disease. Disclosure of Interest : None Declared