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Aim: This study aimed to investigate the associations between single nucleotide polymorphisms (SNPs) of IL-6 (-174G/C), microRNA146a (rs2910164C/G) and MALAT1 (rs619586A/G) and susceptibility to rheumatoid arthritis (RA) in Egyptians. Methods: SNPs were genotyped in 101 RA patients and 104 controls. Expression levels were evaluated either by Enzyme-linked immunosorbent assay (ELISA) for IL-6 or quantitative real-time PCR (qRT-PCR) for miR-146a and MALAT1. Results: IL-6-174 GC (OR = 3.422) genotype, IL-6-174 C allele (OR = 2.565), miR-146a (rs2910164) CG (OR = 2.190) and MALAT1 (rs619586) AA (OR = 4.125) genotypes and A allele (OR = 6.122) could be considered as risk factors for RA. An increase in the expression of IL-6, miR-146a and MALAT1 was detected in RA patients, which was independent of any SNP. Conclusion: SNPs of IL-6, miR-146a and MALAT1were linked to RA predisposition in Egyptians.

Background: miR-210, a key hypoxamiR, regulates hypoxia and inflammation-linked hypoxia. Systemic lupus erythematosus (SLE), a chronic autoimmune disease, is responsible for many pathological disorders, including photosensitivity., Objective: This study aimed to find the correlation between circulating miR-210/HIF-1α levels and photosensitivity in SLE patients and other SLE-associated pathological complications in a single-center case-control study., Methods: The study population comprised 104 SLE Egyptian patients with photosensitivity, 32 SLE patients without photosensitivity, and 32 healthy subjects. SLE activity was assessed for all patients using the SLE Disease Activity Index (SLEDAI). Clinical complications/manifestations and hematological/serological analyses were recorded. HIF-α concentration was investigated by ELISA, and miR-210 expression was analyzed by qRT-PCR., Results: The results revealed that circulating miR-210 was significantly increased in the SLE/photosensitivity group versus the SLE and control groups. The additional occurrence of malar rash, oral ulcers, renal disorders, or hypertension resulted in a higher expression of miR-210. SLEDAI activity status showed no effect on miR-210. Erythrocyte sedimentation rate, white blood cells, hemoglobin, platelets, patient age, and disease duration were positively correlated with circulatory miR-210. HIF-α concentration was significantly induced in the SLE/photosensitivity group versus the SLE and control groups. In SLE/photosensitivity, the presence of renal disorders and hypertension resulted in the highest HIF-α concentrations. A strong positive correlation was recorded between HIF-α concentration and circulatory miR-210 in SLE/photosensitivity patients (r = 0.886)., Conclusion: The dysregulation of circulating miR-210/HIF-1α levels in SLE/ photosensitivity patients is controlled by the presence of additional pathological complications, and results suggest that the hypoxia pathway might interact positively with the pathogenesis and disease progression of SLE., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

microRNA-146a (miR-146a) plays an essential role in immune anomalies and organ injury of systemic lupus erythematosus (SLE) by regulating the disease's inflammation and complications. Here, we analyzed the expression of miR-146a in SLE and a panel of pro-inflammatory cytokines (IL-1, IL-6, IL-8, IL-17, and TNF-α). Association between all measured parameters and the disease's clinical manifestation and response to treatment was monitored. Our study populations were 113 SLE patients and 104 healthy volunteers. miR-146a expression in peripheral blood mononuclear cells (PBMCs) was measured by quantitative real-time PCR (RT-qPCR). The content of the plasma cytokines (IL-1β, IL-6, IL-8, IL-17, and TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA). Compared with healthy controls, miR-146a expression was significantly increased ( p < 0.05) in lupus patients. The analysis of the receiver operator characteristic curve (ROC) of miR-146a showed 91% sensitivity and 70% specificity. IL-1β, IL-6, and IL-17 cytokines were significantly increased ( p < 0.001), while IL-8 and TNF-α were significantly decreased ( p < 0.001) in SLE patients against controls. The expression of miR-146a and TNF-α was upregulated considerably in SLE patients with severe disease activity. miR-146a expression was positively correlated with IL-6. Our results pointed to the elevation of miR-146a as a trade marker of SLE patients. Reduction of IL-8 and TNF-α in combination with an elevation of IL-1β, IL-6, and IL-17 might refer to miR-146a's dual effect in controlling inflammation in lupus. Although we shed some light on the role of miR-146a in SLE, further study is recommended to improve our results.

Objective: MicroRNAs are fine regulators for gene expression during the post-transcriptional stage in many autoimmune diseases. HypoxamiRs (miR-210 and miR-21) play an important role in hypoxia and in inflammation-associated hypoxia. Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that would potentiate many pathological complications, including hemolytic anemia. This study aimed to investigate the role of hypoxamiRs in SLE/hemolytic anemia patients., Methods: This work was designed to analyze the circulating levels of↱ the miR-210 and miR-21 expressions and hypoxia-inducible factor-1α (HIF-α) in SLE/hemolytic anemia patients. SLE activity was evaluated for all patients by SLE Disease Activity Index (SLEDAI). Clinical manifestations/complications and serological/hematological investigations were reported. HIF-α concentration was assayed by ELISA and expression of miR-21 and miR-210 was analyzed by qRT-PCR., Results: The results indicated that the fold change of the miR-210/miR-21 expressions in plasma was significantly elevated in SLE/hemolytic anemia patients. A strong positive correlation between the miR-210 and miR-21 expression levels was also recorded. Among the associated-disease complications, hypertension, arthritis, oral ulcers, and serositis were associated with a high circulating miR-210 expression, while the occurrence of renal disorders was associated with the increased miR-21 expression. Furthermore, the HIF-α level was remarkably elevated in SLE/hemolytic anemia patients. A high positive correlation was recorded between the HIF-α concentration and miR-210/miR-21 expression levels. The occurrence of oral ulcers, arthritis, and hypertension was associated with the increased HIF-α concentration. On the other hand, SLEDAI and white blood cell count were positively correlated with miR-21/ miR-210. The erythrocyte sedimentation rate was positively correlated with miR-21., Conclusion: The dysregulation of the circulating miR-210/miR-210/HIF-1α levels in SLE/hemolytic anemia patients advocated that the hypoxia pathway might have an essential role in the pathogenesis and complications of these diseases., (© 2022. Huazhong University of Science and Technology.)

Background: Oxidative stress is postulated to have a major role in the pathophysiology of Bechet's Disease (BD). Growing evidence suggests that vitamin D has important roles in enhancing the expression of anti-inflammatory cytokines as well as certain antioxidants. However, there is little evidence currently about the antioxidant properties of vitamin D in BD., Objective: To study the relationship between vitamin D levels and the oxidative stress markers in patients with BD in addition to its association with disease activity and severity., Methods: Sixty BD patients (45 males, 15 females; mean age: 34.2 ± 9.6 years) were enrolled in this study and compared to a sex and age matched control group. Plasma 25-Hydroxy vitamin D (25-OH-D) was measured using Human (25-OH-D) ELISA assay. Plasma malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), superoxide dismutase (SOD) activity, catalase (CAT) activity and total antioxidant capacity (TAC) were determined by spectrophotometric methods in both groups. Plasma calcium (Ca) was measured by ELISA assay., Results: When compared to controls vitamin D, GSH, CAT activity, TAC and Ca were significantly lower in BD patients, while MDA and NO levels were significantly increased in BD patients. Our Results Found that vitamin D was inversely correlated to BD current Activity form (BDCAF), disease severity score, ESR, CRP, MDA and NO, while vitamin D was significantly positively correlated to GSH, SOD, TAC and Ca., Conclusion: Our study confirms that a lower level of vitamin D is associated with the oxidative stress state in BD patients as detected by MDA and NO elevation as well as decreased GSH, SOD activity, CAT activity and TAC. Hence, Vitamin D fortified foods and beverages or supplementation may improve disease severity and oxidative stress in BD patients., (© 2022. The Author(s).)

This study aimed to investigate the genetic polymorphisms of miR-146a SNPs (rs2910164, rs57095329, and rs2431697) in systemic lupus erythematosus (SLE) patients and their association with clinical manifestations. The implication of SNPs on miR-146a expression level was also evaluated. SLE patients (113) and healthy controls (104) were registered in this study. The miR-146a SNPs were genotyped by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Quantitative real-time PCR was used to measure the miR-146a expression in peripheral blood mononuclear cells (PBMCs). Our results showed that the genotype frequency of miR-146a SNPs didn't deviate significantly from the Hardy-Weinberg equilibrium (HWE). The AG genotype and G allele of miR-146a (rs57095329 A/G) might be considered a risk factor for the disease (OR = 2.27; CI: 0.78-6.57 and OR: 2.35; CI: 0.79-6.92 for AG genotype and G allele, respectively). Although, no statistical significance in the distribution of miR-146a SNPs (rs2910164, rs57095329, and rs2431697) was found, indicating the lack of association between the three SNPs and SLE susceptibility. Significantly, the higher frequency of the AA genotype of miR-146a (rs57095329) was associated with pancytopenia (P < 0.05), while the CT genotype of miR-146a (rs2431697) was associated (P < 0.05) with the antiphospholipid syndrome (APS). SLE patients had significantly higher levels of miR-146a compared to controls (P < 0.05). Elevation of miR-146a was independent of any SNP genotypes. In conclusion, this pilot study shows no association between miR-146a SNPs in our population group and susceptibility to lupus. Studies concerning other miRNAs in larger sample sizes are essential for a better understanding of their role in susceptibility to SLE disease., Competing Interests: The authors declare that they have no conflict of interest., (© 2022 The Authors.)

Objective: Cytokine polymorphisms have been associated with systemic lupus erythematosus (SLE) pathogenicity. Interleukin 27 (IL-27) is an important one of pro-/anti-inflammatory cytokine. It has been reported in various Th1/Th17-mediated inflammatory disorders, and even in Th2-complexed diseases, such as SLE. In our preliminary study, the aim was to investigate the potential roles of single nucleotide polymorphism (SNP) -964A/G (rs153109) and + 2905 T/G (rs17855750) in an IL-27p28 gene on susceptibility to SLE., Methods: The 112 Egyptian SLE patients against 101 healthy persons were enrolled in this work. The polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) is used for genotyping IL-27 SNPs., Results: No significant variations were found between patients and control in the genotype and allele frequencies of IL-27p28 (-964A/G). SLE patients have a significant increase in the frequency of IL-27p28 (+ 2905 T/G) TG genotype (P < 0.01) and G allele (P < 0.01) compared to controls. Complete disappearance of GG genotype was demonstrated in both groups. G allele might have considered a disease risk factor with odd ration (OR) = 9.184. From four possible haplotypes, the frequency of AT haplotype elevated in both examined groups., Conclusion: This was the first study on the Egyptian population for studying the relation between IL-27 SNPs and SLE. Our preliminary study indicated that both TG genotype and G allele of IL-27p28 (+ 2905 T/G) could consider risk factors for SLE. Key Points • This article provides an information about the relation between systemic lupus erythematosus and interleukin-27 cytokine by detection single nucleotide polymorphism., (© 2021. International League of Associations for Rheumatology (ILAR).)

Background: Systemic lupus erythematosus (SLE) has a variable natural history and clinical characteristics., Objectives: This study aims to evaluate the clinical and immunological characteristics, and assess the disease accrual of an Egyptian SLE cohort., Methods: The study included 569 SLE patients who were collected from three different centers; demographic, laboratory data, cumulative manifestations, and comorbidities were assessed (characteristics at the time of diagnosis were recorded retrospectively, while current clinical data were recorded cross-sectionally). Evaluation of disease activity was done using Systemic Lupus Erythematosus Disease Activity Index score (SLEDAI) and damage by Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SDI)., Results: The median age of patients at disease onset was 25.0±10.5 years, the median disease duration was 4.0 (6.5) years, the female to male ratio was (12.5:1), and the median SLEDAI was 12.0±14.0. Family history of SLE was noticed in 4%. Antinuclear antibody was positive in all patients and 86% had positive anti-double-stranded DNA. Arthritis/arthralgia was the most frequent presenting symptom (44%) followed by fever (39%). Along the disease course; alopecia was the most common clinical manifestation (76.1%), followed by constitutional symptoms (75.9%), and nephritis (65.7%). Three hundred and five patients encountered organ damage (SDI >1); kidney damage was the most frequent (32%), followed by cardiovascular damage (24.3%). Neutropenia, hypocomplementemia, arthritis, hypertension, longer disease duration, and higher disease activity were found to be independent risk factors for disease damage., Conclusions: There are some diversities and similarities in our findings compared to the previously reported data. Arthritis is the most common presenting symptom, while alopecia is the most frequent clinical finding, and a higher prevalence of nephritis was reported. Renal damage is the most frequent outcome., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: Behçet's disease (BD) is a chronic autoimmune vasculitic disorder of unclear pathogenesis. CCN2/CTGF (connective tissue growth factor) is one of the CCN family members which carry out pro-angiogenic biological functions and play an important role in inflammatory and autoimmune diseases. The aim of the present study was to assess CCN2 plasma concentrations in BD patients and to analyze their association with clinical features of the disease, activity and laboratory parameters., Methods: We included 87 BD patients and 60 healthy control subjects matched for age and gender. Demographic, clinical, disease activity and severity data were recorded. Plasma CCN2 concentrations were measured using enzyme-linked immunosorbent assay., Results: The plasma concentrations of CCN2 in BD patients were significantly elevated compared to healthy controls. The mean plasma CCN2 levels in patients with major organ involvement were significantly higher than those without. Patients who received steroids or cyclophosphamide showed a significant reduction in CCN2 levels. This was confirmed by the results of multivariate analysis. Patients with active ocular disease had a significant increase in CCN2 compared to the inactive group. On the other hand, CCN2 levels were not significantly correlated with overall disease activity and severity scores., Conclusion: Behçet's disease patients showed a significant increase of CCN2 levels, especially in the group of patients with major organ involvement. A significant reduction of these levels was found in patients who received steroids or cyclophosphamide. Larger studies with further investigations of the precise role of CCN2 in BD pathogenesis might lead to novel therapies for the clinical management of this disease., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

There are a limited number of studies that report the polarization of the immune system toward the production of T helper 1 (Th1), Th2, or Th17-type cytokines in patients with Behçet's disease (BD). Here, we aimed to detect the presence of various cytokines in serum samples of Egyptian BD patients and to determine the correlation between their production levels and clinical manifestations. To that aim, serum levels of IFN-γ, IL-10, IL-6, and IL-17 measured by ELISA were determined in BD patients with active or inactive disease to evaluate their clinical relevance. The results of the present study show significantly elevated levels of IL-17 and IL-6, as well as a reduction in IL-10, and no change in IFN-γ, in sera of BD patients, as compared to the healthy control group. Moreover, IL-6 serum levels were increased in BD patients in active stages of disease and correlated with arthritic manifestations. On the other hand, IL-10 serum levels were significantly decreased in patients with gastrointestinal tract complications. Furthermore, a positive correlation was observed between IL-10 serum levels and ocular manifestations in BD patients, in contrast to those of IL-17, showing no correlation with the different clinical manifestations. Taken together, the magnitude of IL-6 serum levels could be a potential marker for arthritic manifestations and disease activity, whereas those of IFN-γ, IL-10, and IL-17 cannot be considered predictors for different clinical manifestations in patients with BD.

miRNAs are noncoding RNA that play a critical role as fine regulators of gene expression at the posttranscriptional level within cells in numerous autoimmune diseases. miR-221/222 play a role in cancer by regulating cell proliferation, invasion and apoptosis. However, there have been insufficient studies on their role in rheumatoid arthritis (RA). This work is designed to analyze the miR-221/222 expression patterns in peripheral blood mononuclear cells (PBMCs) of patients with RA in comparison with healthy controls using quantitative RT-PCR, in a group of 30 RA patients and 20 healthy controls. The fold change of miR-221/222 expression in PBMCs was significantly elevated (p < 0.01) in RA patients compared with healthy controls. A positive correlation between expression levels of miR-221 and miR-222 was recorded (r = 0.303; p < 0.05). High miR-221/222 expression levels appeared to be elevated with high activity. miR-222 expression in high activity group of RA patients was significantly increased in relation to moderate (p < 0.01) and low (p < 0.001) activity ones with positive correlation (r = 0.363; p < 0.05) between the progress of disease activity and change in miR-222 expression level. ROC analysis showed a sensitivity of 70% and specificity of 75% for miR-221. In miR-222, the sensitivity of 80% and specificity of 70% were recorded. Our data shed some light on the role of miR-221/222 expression in RA patients, and their great potential value as new novel noninvasive biomarkers for disease detection. Therefore; further investigations are warranted to fully elucidate their role in rheumatoid.

Background: Few studies have reported a possible involvement of pleiotrophin (PTN) in the pathophysiology of osteoarthritis (OA) and very little is known about its role in rheumatoid arthritis (RA). This study is to measure PTN in the sera and synovial fluids in RA and OA and to assess its relation to activity, functional class and radiological staging., Subjects and Methods: Serum and synovial fluid samples were collected from 35 RA patients and 40 knee OA patients and serum samples were withdrawn from 20 healthy controls. Demographic, clinical and serological data were prospectively assessed. Functional and radiographic grades were also assessed. Serum and synovial fluid PTN levels were measured using enzyme-linked immunosorbent assay (ELISA)., Results: There was no statistical significant differences (p > 0.05) on comparing the mean PTN level in sera of RA, OA patients and healthy controls. However the mean synovial fluid level of PTN in both patient groups was significantly higher than mean serum level (p < 0.001). Significant correlations between the serum PTN level and both morning stiffness duration (p = 0.008) and mHAQ score (p = 0.039) were only observed in RA patients., Conclusion: Our results point to a possible important role of PTN in RA and OA. We firstly report a serological pattern of PTN in the sera and synovial fluids of RA patients. However its implementation as a disease marker or a potential target therapy in both diseases awaits larger studies and further investigations.

Aim of the Work: This study aims to assess Growth differentiation factor-15 (GDF-15) level in Scleroderma patients and its relation to disease manifestations., Patients and Methods: This study included 55 scleroderma patients and 40 age and sex matched healthy volunteers. All patients were subjected to full history taking, thorough clinical examination, and laboratory investigations. GDF-15 serum levels were analyzed in patients and controls using human GDF-15 immunoassay Quantikine ELISA kit., Results: The GDF-15 serum level was significantly higher in Systemic sclerosis (SSc) patients in comparison to healthy control individuals, p-value = 0.004. In addition, the GDF-15 serum levels increased in a significant way in patients with diffuse SSc than those with limited SSc, p = 0.026. Also, we had discovered a significant positive correlation between serum GDF-15 levels and the modified Rodnan score of the SSc patients, r = 0.442, p = 0.001 and a significant association was found between high GDF-15 level and SSc patients with interstitial pulmonary fibrosis (IPF) as compared to healthy controls (p = 0.002). However, no significant difference was found between SSc patients without IPF and healthy subjects regarding GDF-15 level (p = 0.106)., Conclusion: GDF-15 serum levels were elevated in patients with SSc and correlated with the extent of skin fibrosis, and it was found to be higher in SSc patients with IPF. Such results may suggest a pivotal role of GDF-15 in fibrotic changes in SSc, and GDF-15 could be a treatment target in SSc patients in future.

A triggering receptor expressed on myeloid cells-1 (TREM-1) is a member of the immunoglobulin superfamily with an established role in innate and adaptive immune response. We aimed to determine the plasma concentrations and clinical association of sTREM-1 in Systemic Lupus Erythematosus (SLE) patients. Plasma from 79 SLE patients and 35 normal healthy subjects were assayed for sTREM-1 and IL-6 levels using Enzyme Linked Immunosorbant Assay (ELISA). The clinical disease characteristics and serological data were prospectively assessed. Disease activity was scored using the SLE disease activity index. We detected significantly higher levels of sTREM-1 in plasma of SLE patients than the healthy control group. We also detected high sTREM-1 levels in subgroups of patients with neuropsychiatric manifestations (NPLE) and patients with the total high disease activity and NPLE activity. In addition, sTREM-l levels were significantly correlated with parameters of disease activity, i.e. SLEDAI score, IL-6, hypoalbuminemia. On the other hand, we did not find significant differences in sTREM-1 levels in relation to age, disease duration, medications, ESR, other organ system involvement, or the presence of anti-dsDNA. Our preliminary data indicated that sTREM-1 levels may be an additional useful marker of disease activity in SLE. It also highlights its importance in patients with NPLE. An additional prospective longitudinal study should be carried out to support these findings.

Aim: Growth arrest specific protein 6 (Gas-6) and its tyrosine kinase receptor Axl plays an important role in apoptosis, and regulation of innate immune response, therefore, we investigated their plasma concentrations in Rheumatoid arthritis (RA) patients and correlated them to clinical, laboratory and radiological parameters of the disease., Methods: Plasma from 77 RA patients and 50 normal healthy subjects were assayed for plasma Gas6 and Axl levels. Demographic, clinical and serological data were prospectively assessed. Rheumatoid arthritis disease activity was assessed using 28-joint Disease Activity Score (DAS-28) and functional capacity by modified health assessment questionnaire (mHAQ). Standardized x-rays for hands and feet were done to all participants., Results: The level of Gas6 and Axl were significantly decreased in the RA patients compared to those of the healthy control subjects. Levels of Gas6 correlated positively with Axl levels in both patients and healthy control. Gas6 levels were remarkably reduced in those patients with erosive RA than those without. Levels of Gas6 were found to be negatively correlated with the presence of erosive disease and positively correlated with DAS-28, ESR, Leucocytosis and IL6., Conclusion: The plasma concentrations of Gas6 and Axl are altered in RA patients and thus may have a role in RA pathogenesis. Further mechanistic studies on the involvement of all TAM receptors tyrosine kinases pathway in RA are needed to help in understanding the pathogenesis and possibly aid in diagnosis and future treatments of RA especially for patients with erosive disease., (© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Behcet's disease (BD) is a chronic multisystem inflammatory disorder of unclear etiology. Vascular inflammation, endothelial dysfunction and angiogenesis may be in part responsible for the pathogenesis of BD. Angiopoietin-1 (Ang-1) is a recent angiogenic mediator. The aim of the present study was to assess Ang-1 in the plasma of BD patients as well as to analyze its association with clinical, and laboratory parameters of the disease. The present study included 47 BD patients and 30 age- and gender-matched healthy controls. Demographic, clinical, disease activity and severity were prospectively assessed. Plasma Ang-1 levels were measured using enzyme-linked immunosorbent assay. The plasma level of Ang-1 in BD patients was significantly lower than healthy controls (p = 0.005). Plasma Ang-1 level in patients with vascular affection was significantly lower than those without vascular affection (p = 0.045). Levels of Ang-1 showed a significant positive correlation with steroid dose. Patients who received cyclophosphamide or steroids showed a significant increase in plasma Ang-1 level. This was further confirmed by the results of the multivariate analysis. There was no significant association between plasma Ang-1 levels and other clinical manifestations or disease activity and severity. Plasma Ang-1 levels were diminished in our BD patients especially in patients with vascular involvement. Larger studies with further investigations of the precise role of Ang-1 in the pathogenesis of BD are needed and might lead to novel therapies for the clinical management of BD.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Cytokine gene polymorphisms play an important role in SLE. Thus, this study aimed to investigate the associations between interleukin 6 (IL-6) and interleukin 10 (IL-10) promoter single-nucleotide polymorphisms (SNPs) and their susceptibility to SLE and the implications for plasma levels. We genotyped IL-6-174G/C (rs1800795) using mutagenically separated polymerase chain reaction (MS-PCR) and IL-10-1082G/A (rs1800896) and -819C/T (rs1800871) using sequence specific primer polymerase chain reaction (SSP-PCR) in 100 Egyptian patients and 119 controls. The plasma levels of IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). There was significant increase in the frequency of IL-6 (-174) GG genotype (P < 0.05) and G allele (P < 0.01) compared to controls. A significant increase in the distribution of IL-10 (-1082G/A) GG (P < 0.05) and AA (P < 0.05) genotypes and a significant reduction in the frequency of GA genotype (P < 0.05) was found in SLE patients. The mean serum concentration of IL-6 (P < 0.001) and IL-10 (P < 0.001) was significantly elevated in SLE patients compared to healthy controls. There was no significant association of the most common clinical findings and IL-6 and IL-10 gene polymorphisms in SLE patients. In conclusion, our preliminary study indicated that both GG genotype and G allele of IL-6 (-174G/C) could be considered as risk factors for SLE. In addition, the polymorphisms at IL-10 (-1082 G/G and AA) may play a role in SLE susceptibility in Egyptian patients. Larger prospective studies are needed to confirm our findings., (© The Author(s) 2015.)

Aim: Imbalance of T-helper-cell (TH) subsets (TH1/TH2/TH17) and regulatory T-cells (Tregs) is suggested to contribute to the pathogenesis of Systemic lupus erythematosus (SLE). Therefore, we evaluated their cytokine secretion profile in SLE patients and their possible association with disease activity., Methods: Sixty SLE patients, 24 rheumatoid arthritis (RA) patients and 24 healthy volunteers were included in this study. Demographic, clinical, disease activity and serological data were prospectively assessed. Plasma cytokines levels of TH1 (IL-12, IFN-γ), TH2 (IL-4, IL-6, IL-10), TH17 (IL-17, IL-23) and Treg (IL-10 and TGF-β) were measured by enzyme linked immunosorbent assays (ELISA)., Results: SLE patients were found to have significantly higher levels of IL-17 (p<0.001), IL-6 (p<0.01), IL-12 (p<0.001) and IL-10 (p<0.05) but comparable levels of IL-23 and IL-4 and slight reduction (but statistically insignificant) of TGF-β levels compared to controls. IL-6, IL-10 and IL-17 were significantly increased (p<0.05) with disease activity. The RA group exhibited significantly higher levels of plasma IL-4 (p<0.01), IL-6 (p<0.05), IL-17 (p<0.001), IL-23 (p<0.01) and TGF-β (p<0.5) and lower IFN-γ (p<0.001) and IL-10 (p<0.01) than those of healthy subjects., Conclusion: Our study showed a distinct profile of cytokine imbalance in SLE patients. Reduction in IFN-γ (TH1) and TGF-β1 (Treg) with the elevation in IL-6 and IL-17 (TH17) could imply skewing of T-cells toward TH17 cells. Breaking TH17/Treg balance in peripheral blood may play an important role in the development of SLE and could be responsible for an increased pro-inflammatory response especially in the active form of the disease., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A growing body of evidence suggests that anti-complement-1q (anti-C1q) antibodies are elevated in a variety of autoimmune disease. Therefore, we investigated their prevalence and clinical significance in plasma of patients with hepatitis C virus (HCV) genotype IV in the presence and absence of autoimmune extra hepatic manifestations in comparison to normal healthy individuals. Plasma Anti-C1q Abs levels were assessed by an Enzyme Linked Immunosorbant Assay in 91 chronic HCV-infected patients (51 with and 40 without autoimmune rheumatic manifestations) and 40 healthy volunteers matched for age and gender. Epidemiological, clinical, immunochemical and virological data were prospectively collected. Positive Anti-C1q antibodies were more frequent among HCV patients with extra-hepatic autoimmune involvement, than those without and healthy control subjects. No significant correlations were found between Anti-C1q levels with either the liver activity or the fibrosis scores. In HCV-patients with autoimmune involvements, plasma Anti-C1q levels were significantly higher in patients with positive cryoglobulin, and in those with lymphoma than in those without. These results were confirmed by multivariate analysis. Further large scale longitudinal studies are required to assess and clarify the significance and the pathogenic role of anti-C1q antibodies among HCV infected patients with positive cryoglobulinaemia and lymphoma.

Cytokines play critical roles in the pathogenesis of Behçet's disease (BD). They mediated many of the effectors and regulatory functions of immune and inflammatory responses. Many studies have linked Interleukin-6 (IL-6) and Interleukin-10 (IL-10) pathologically to BD. Thus, this study aimed to investigate the associations between IL-6 and IL-10 promoter single-nucleotide polymorphisms (SNPs) and the susceptibility to BD and their implication on plasma levels. We genotyped IL-6 -174 G/C (rs1800795) using Mutagenically Separated Polymerase Chain Reaction PCR (MS-PCR) and IL-10 -1082 G/A (rs1800896) and -819 C/T (rs1800871) using Sequence Specific Primer PCR (SSP-PCR) in 87 Egyptian patients and 97 controls. The plasma levels of IL-6 and IL-10 were measured using Enzyme-linked Immunosorbent Assay (ELISA). Significant increase in the frequency of -1082 GG genotype (P<0.05, OR=2.25, 95%CI=1.03-4.91) and significant decrease in the frequency of -1082 GA genotype (P<0.05, OR=0.53, 95%CI=0.29-0.96) was demonstrated in BD patients compare to controls. Patients with genital ulcer had significantly lower frequency of -1082 GG (P<0.05, OR 0.2, 95% CI=0.04-0.99) and G allele (P<0.05, OR=0.28, 95%CI=0.08-0.93), while patients with ocular manifestations had significantly higher frequency of -1082 G allele (P<0.01, OR=2.28, 95%CI=1.19-4.36). BD patients had significantly higher level of IL-6 (P<0.001) and significantly lower level of IL-10 (P<0.001) compared to controls. The changes in the level of cytokines were independent of any genotype of IL-6 or any genotype/haplotype of IL-10. Patients with active disease state had significantly higher level of IL-6 compared to patients in remission (P<0.05). In conclusion, our preliminary study indicates that the polymorphism at IL-10 -1082 G/A may play a role in BD susceptibility. The significant increase in IL-6 level and the significant decrease in IL-10 level in BD patients were independent of any particular genotype in IL-6 or any particular genotype/haplotype in IL-10., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Aim: The aim of our study was to determine the prevalence of anti-C1q antibodies and their possible association with clinical presentation in Behcet's disease (BD) patients with special emphasis for patients with vascular involvement., Methods: Plasma anti-C1q Abs levels were measured using an enzyme-linked immunosorbent assay in 51 BD patients and 25 age- and gender-matched healthy controls., Results: We found elevated concentrations of anti-C1q more frequently in patients with BD (18 %) than in healthy controls (8 %). The highest prevalence was found in patients with vascular BD (42 %) which was significantly higher than patients without vascular BD and healthy controls (p = 0.025). Furthermore, patients with vascular BD had the highest mean anti-C1q levels when compared to BD patients without vascular involvement or healthy control subjects (p = 0.015). We did not find significant differences in the prevalence of any other organ involvement between BD patients with elevated vs. normal anti-C1q ab levels. Anti-C1q ab levels positively correlated with ESR (r = 0.383, p = 0.006) and negatively with C4 (r = -0.304, p = 0.030)., Conclusion: In conclusion, we found an increased prevalence of anti-C1q autoantibodies in BD patients with vascular involvement. Further large scale longitudinal studies are required to assess and clarify the significance and the pathogenic role of anti-C1q antibodies in BD and other autoimmune diseases in which vasculitis is a component.

AIM: The aim of our study was to determine the prevalence of anti-C1q antibodies and their possible association with clinical presentation in Behcet's disease (BD) patients with special emphasis for patients with vascular involvement. METHODS: Plasma anti-C1q Abs levels were measured using an enzyme-linked immunosorbent assay in 51 BD patients and 25 age- and gender-matched healthy controls. RESULTS: We found elevated concentrations of anti-C1q more frequently in patients with BD (18 %) than in healthy controls (8 %). The highest prevalence was found in patients with vascular BD (42 %) which was significantly higher than patients without vascular BD and healthy controls (p = 0.025). Furthermore, patients with vascular BD had the highest mean anti-C1q levels when compared to BD patients without vascular involvement or healthy control subjects (p = 0.015). We did not find significant differences in the prevalence of any other organ involvement between BD patients with elevated vs. normal anti-C1q ab levels. Anti-C1q ab levels positively correlated with ESR (r = 0.383, p = 0.006) and negatively with C4 (r = -0.304, p = 0.030). CONCLUSION: In conclusion, we found an increased prevalence of anti-C1q autoantibodies in BD patients with vascular involvement. Further large scale longitudinal studies are required to assess and clarify the significance and the pathogenic role of anti-C1q antibodies in BD and other autoimmune diseases in which vasculitis is a component.

Aim: Osteopontin (OPN) is a multifunctional molecule highly expressed in chronic inflammatory and autoimmune diseases. We aimed to assess the plasma OPN levels in Behcet's disease (BD) patients and identify potential associations between these levels with disease activity, severity and clinical manifestations with special emphasis on vascular affection., Methods: We studied 55 BD patients and 31 age- and gender-matched healthy controls. Demographic, clinical and serological data were prospectively assessed. Activity and severity of BD were assessed using clinical scores and laboratory parameters. Plasma OPN levels were measured using enzyme-linked immunosorbent assay (ELISA)., Results: Plasma OPN levels were significantly higher in patients with BD compared to healthy controls (p < 0.000). The means for plasma OPN levels in active and inactive BD patients were significantly higher than that for the normal controls (with p < 0.000 and p = 0.002 respectively). The mean OPN levels significantly associated with the BD clinical severity score from mild to severe (p = 0.011). BD patients with vascular involvement had significant elevation of plasma OPN levels than those without (P = 0.03). OPN levels positively correlated with severity score, IL6, hsCRP, ESR, leucocytes count and neutrophil count., Conclusion: Plasma OPN levels were higher in BD patients than in healthy controls and were found to be associated with disease activity, severity and vascular involvement. To confirm our results we propose that larger scale, multicentre studies with longer evaluation periods are needed.

Purpose: The aim of the present study was to investigate plasma concentrations of Gas6 and its soluble tyrosine kinase receptor sAxl in Systemic lupus erythematosus (SLE) and Behçets disease (BD) patients and to correlate those levels with clinical and laboratory manifestations of the diseases., Methods: The study included 89 female SLE and 49 male BD patients. Twenty-seven age and sex matched healthy volunteers served as controls. All patients were subjected to full clinical examination, laboratory investigations and assessment of disease activity. Plasma concentrations of Gas6 and sAxl were quantified using ELISA technique., Results: The level of Gas6 and Axl were significantly altered in the SLE patients (p < 0.001) and in the BD patients (p 0.001 and 0.04 respectively) compared to those of the control. In SLE, the Gas6 was remarkably lower in those with class 1 lupus nephritis and in those with neuropsychiatric manifestations. In the BD patients, the level of Axl was significantly increased in those with neurological disease activity. The number of lymphocytes significantly negatively correlated with the gas6 and Axl levels significantly correlated with the number of neutrophils and negatively with the lymphocytic count in the BD patients., Conclusion: The plasma concentrations of Gas6 and Axl were significantly altered in SLE and BD patients, suggesting that the Axl receptor shedding is an active process affected by and influences Gas6-mediated Axl-signaling in both diseases. Special attention is required in SLE patients with early lupus nephritis and neuropsychiatric manifestations and BD patients presenting with neurological disease activity. The relation with lymphocytes and neutrophils in BD throws light on the role of gas6 and Axl on their known resistance to cell death. Although the mechanisms responsible for the initiation of BD remain to be clarified, the role of the apoptotic process seems critical throughout the disease.

Owing to the suggested role of osteopontin (OPN) in inflammation, autoimmunity and fibrosis, we investigated their serum concentrations in chronic hepatitis C virus (HCV) infected patients with and without autoimmune manifestations and correlated those levels to clinical manifestations and the histological severity of hepatic fibrosis. A total of 70 chronic HCV-infected patients (35 with and 35 without autoimmune rheumatic manifestations‏) were compared with 35 healthy volunteers matched for age and gender. Epidemiological, clinical, immunochemical and virological data were prospectively collected. OPN serum levels were assessed by an Enzyme Linked Immunosorbant Assay. The mean serum OPN levels were higher in HCV patients with autoimmune rheumatologic manifestations and in patients without; than that for the normal controls (p = 0.000). The mean OPN values progressively increased by increasing severity of liver fibrosis (p = 0.009). Multivariate analysis revealed that the presence of rheumatologic manifestations had the highest predictive value (b = 7.141, Beta = 0.414, p = 0.000) followed by liver fibrosis (b = 4.522, Beta = 0.444, p = 0.000) on the variation of OPN levels in our HCV patients. Among the group of patients with HCV and rheumatologic involvement, OPN serum levels were higher in patients with positive cryoglobulin and rheumatoid factor than in those without, and with systemic vasculitis than in those without. Correlation analysis didn't reveal any statistical significance of OPN with age, serum albumin, aminotransferases and viral load. Our data suggests OPN as a promising marker for HCV associated autoimmune rheumatologic involvement, particularly with regard to development of vasculitis and cryoglobinemia. In addition, it could serve as a biomarker to evaluate the severity of liver damages in HCV infected subjects.

Objective: To assess the level of B-cell activating factor belonging to the tumor necrosis factor family (BAFF) also known as B-lymphocyte stimulator (BLyS) and A proliferation-inducing ligand (APRIL) in the serum of Juvenile idiopathic arthritis (JIA) patients and to detect their relation to the clinical manifestations and disease activity in the different subtypes of the disease., Methods: Seventy-four consecutively recruited JIA patients were clinically examined, the Juvenile arthritis disease activity score in 27 joints (JADAS-27) calculated and Childhood Health Assessment Questionnaire (CHAQ) used to measure the functional status. Thirty-four healthy matched children served as controls. Routine laboratory examinations were recorded and serum BAFF and April were determined., Results: The JIA patients were 20 systemic-onset, 31 oligoarticular and 23 polyarticular. Serum BAFF and APRIL were elevated in JIA patients being higher in systemic onset and both significantly correlated. APRIL significantly correlated with both JADAS-27 and CHAQ scores while BAFF correlated only with JADAS-27. The APRIL serum levels were significantly associated with the presence of RF and ANA. The BAFF serum levels were significantly higher in oligoarticular onset JIA patients with uveitis compared to those without., Conclusion: Our results suggest increased BAFF and APRIL serum levels in JIA patients denoting their possible role in the disease and calling for additional research to elucidate the intrinsic mechanisms explaining APRIL and BAFF over expression., (Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Systemic sclerosis (SSc) is a multisystem disease in which interplay between inflammation, autoimmunity and fibrosis appears to play an indispensable role. Owing to the suggested role of cyclooxygenase-2 enzymes (Cox-2) in inflammation and fibrosis, we investigated their serum concentrations in SSc patients and their clinical and laboratory associations. Serum from 49 patients with SSc, 28 of whom had limited cutaneous SSc (lSSc) and 21 had diffuse cutaneous SSc (dSSc) subtypes, and from 27 healthy subjects were assayed for Cox-2 and TNF by enzyme-linked immunosorbent assay (ELISA). Demographic, clinical, autoantibodies and serological data were prospectively assessed. The analysis revealed that patients with lSSc had higher levels of serum Cox-2 than controls. Serum Cox-2 levels were increased in SSc patients with arthritis and digital ulcers; on the contrary, these were diminished in those with associated pulmonary fibrosis. An additional prospective large scale, longitudinal study should be carried out to support these findings and to reveal the mechanistic connections between Cox-2 levels and SSc disease manifestations.

Objective: To evaluate the clinical significance of anti-angiogenic receptor cluster of differentiation 36 (CD36) in serum of patients with SSc., Methods: We studied 47 SSc patients (28 with lcSSC and 19 with dcSSC) and 38 age- and gender-matched healthy controls. Demographic, clinical, autoantibodies and serological data were prospectively assessed. Peripheral vascular affection was classified into mild, moderate, severe or end-stage based on a vascular severity scale. Soluble CD36 (sCD36) serum levels were measured using ELISA., Results: Serum sCD36 levels were significantly higher in patients with SSc compared with healthy controls (P = 0.045). When the patients were divided into clinical subsets, sCD36 was higher in lcSSc than in healthy controls (P = 0.03). Levels of sCD36 were found to be positively correlated with pulmonary artery systolic pressure (PASP) and negatively correlated with percentage diffusing lung capacity for carbon monoxide (DL(CO)). In the multivariate analysis, 50% of the variation of sCD36 levels could be explained by elevated PASP (0.000), telangiectasias (0.026) and increasing vascular severity (P = 0.003)., Conclusion: Serum sCD36 levels were higher in SSc patients (particularly the limited subset) than in healthy controls and were found to be correlated with PASP and vascular severity. We conclude that sCD36 may be a marker for elevated PASP and vascular involvement in SSc. To confirm our results we propose that larger scale, multicentre studies with longer evaluation periods are needed.

Juvenile idiopathic arthritis (JIA) is an autoimmune diseases characterized by chronic arthritis and systemic manifestations. Autoimmune diseases can affect the upper airways including the larynx. The aim of this study was to investigate laryngeal involvement in JIA patients and its possible association with JIA disease parameters. Fifty consecutive JIA patients were screened for laryngeal abnormalities using flexible fiberoptic laryngoscope and laryngeal computerized tomography. Laryngeal abnormalities were detected in nine (18%) of our cases, with cricoarytenoiditis in six cases (12%) and a rheumatoid nodule in the pyriform fossa in only one case (2%). Diffuse congestion and edema of the posterior part of the larynx with normal vocal cord mobility was detected in two cases (4%). In our study, laryngeal abnormalities were significantly higher in patients with polyarticular seropositive disease subtype and also were significantly higher in patients with longer disease duration, higher disease activity scores, and those with erosive disease. JIA may affect the larynx. Laryngeal involvement in JIA patients is more in polyarticular seropositive cases. JIA patients have to be subjected to thorough otolaryngologic examination for early diagnosis and prompt management.

Objective: To investigate the vestibular dysfunction in a cohort of patients with systemic sclerosis (SSc) and to correlate the findings with disease parameters and microvascular involvement., Methods: Vestibular affection was assessed in 30 female SSc patients and 29 age-matched healthy females subjects by using the computerized dynamic platform posturography (CDP). Assessment of microvasculature was done by nailfold videocapillaroscopy (NVC). The main clinical correlates of disease, such as renal function, skin, articular and lung involvement, were evaluated by clinical and instrumental investigations., Results: Subtle vestibular dysfunction was detected in 33% of SSc patients. They exhibited significant decrease in their vestibular ratio values compared to controls (P=0.01). There was a statistical significant association of vestibular affection with both Rodnan's skin score and vascular severity score. Moreover a significant association was found between vestibular dysfunction and NVC patterns. On the other hand, no correlation was observed between vestibular impairment with age, disease duration, disease subsets, autoantibodies and the other clinical disease parameters., Conclusion: Our results showed an evidence of vestibular impairment in patients with SSc. Vestibular dysfunction positively correlates with vascular severity score as assessed by NVC., (Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objective: A proliferation-inducing ligand (APRIL) is a new member of the tumour necrosis factor family which is intimately connected to the regulation of cellular pathways. The aim of this study was to assess serum concentrations of APRIL in systemic sclerosis patients, and to correlate them with the main clinical and serological features of the disease., Methods: Sera from 35 patients with systemic sclerosis, 25 had limited cutaneous and 10 had diffuse cutaneous subtypes, and 35 normal healthy subjects were assayed for APRIL by Enzyme Linked Immunosorbant Assay. Demographic, clinical, autoantibodies and serological data were prospectively assessed., Results: Serum APRIL concentrations were higher in patients with systemic sclerosis and in both its subtypes compared to the healthy controls (p<0.0001 in all). Patients with elevated APRIL levels had significantly higher incidences of myositis than those with normal levels (p=0.04). We did not find significant differences in other organ involvement prevalence between systemic sclerosis patients with elevated vs. normal APRIL levels. In addition, the frequencies of autoantibodies (i.e., anti-topoisomerase I, anti-centromere) were comparable between both groups. Serum APRIL levels were correlated with serum γ-globulins concentrations (r=0.404, p=0.016) but not with C-reactive protein, skin score, nor pulmonary functions. Serum APRIL was also correlated with creatine kinase levels only in systemic sclerosis patients with myositis (r=0.786, p=0.02)., Conclusion: Our preliminary results suggest increased serum APRIL levels in systemic sclerosis patients, particularly in those associated with myositis and hypergammaglobinemia. To confirm our results, we propose that larger scale, multicentre studies with longer evaluation periods are needed., (Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Background: Symmetric polyarthritis associated with hepatitis C virus (HCV) infection frequently displays a clinical picture like rheumatoid arthritis (RA). Antibodies to cyclic citrullinated peptide (CCP) have high specificity for the diagnosis of RA. This study examined the frequency and clinical significance of anti-CCP antibodies in patients with chronic HCV infection, with and without manifestations of joint involvement, compared to RA patients., Methods: Serum anti-CCP antibodies and rheumatoid factor (RF) were evaluated in 30 patients with RA and 47 patients with chronic HCV infection. Of those with HCV infection, 20 patients had chronic HCV infection associated with articular involvement and 27 patients had chronic HCV infection without any articular involvement., Results: Anti-CCP antibody level was positive in 70% of RA patients, 8.5% of HCV-infected patients, and in 20% of HCV patients with articular manifestations. RF was positive in 76% of RA patients and in 60% of HCV patients with articular involvement. Cryoglobulins were found in 29% of HCV-infected patients and in 16% of RA patients. Cryoglobulins were more frequent among HCV patients with articular affection (35%) compared to HCV patients without articular affection (26%)., Conclusions: Although anti-CCP antibodies remain a useful diagnostic tool for RA, their interpretation in HCV-infected patients with arthritis should be applied with caution. The possibility that those patients could be prone to develop RA cannot be ruled out. Those patients need careful clinical and radiological follow-up. Further large-scale studies are warranted.

Systemic Lupus Erythematosus (SLE) is a chronic, systemic autoimmune disease characterized by loss of tolerance to self-antigens. Regulatory T cells (T(REG)) are those CD4+ T cells that constitutively express high levels of CD25 and exhibit powerful suppressive properties. The aim of this work was to quantify CD4+CD25+ (T(REG)) cells and the Mean Fluorescence Index (MFI) of T(REG) in the peripheral blood of patients with SLE and to correlate these findings with their disease activity scores and drug therapy. This study included 24 SLE patients with various disease activity scores (SLEDAI) and 24 healthy age and sex matched controls. Flow cytometry was used to examine the frequency of CD4+CD25+ T cells and the MFI of CD4+CD25+(high) T cells (T(REG)). CD4+CD25+ T cells % and MFI of CD4+CD25+(high) T cells were higher in SLE patients than controls (p value=0.62 and=0.037 respectively) and both CD4+CD25+ T cell % and the MFI of CD4+CD25+(high) T cells showed highly significant correlation with SLEDAI scores (both with a p value<0.001) and were higher in patients taking glucocorticoids than those not on glucocorticoids (p= 0.023, 0.048 respectively). We conclude that the increase in T(REG) cells in our patients may be due to corticosteroid treatment.