Single Nucleotide Polymorphism rs6445975 in the PXK Gene Is Correlated with Susceptibility and Clinical Characteristics of Systemic Lupus Erythematosus.

Background: Recently, genome-wide association studies (GWAS) have discovered several single nucleotide polymorphisms (SNPs) and loci associated with the risk of systemic lupus erythematosus (SLE). rs6445975 (T>G; intronic variant) polymorphism in the PXK gene is one of these loci. However, there was an inconsistency between the results of replicative studies on European and Asia ancestry. This study aimed to assess the possible association between rs6445975 polymorphism with SLE risk in the Iranian population. Methods: Genotype and allele distribution of rs6445975 polymorphism were investigated in 110 patients with SLE and 115 healthy controls in Isfahan University of Medical Sciences, Isfahan, Iran in 2019 via real-time PCR high resolution melting method (HRM). Results: GG and TG genotypes, but not TT genotype, were associated with increased risk of SLE (GG vs TT; OR= 7.538; 95%CI [3.47, 17.066] and TG vs TT; OR=2.21; 95%CI [1.06, 4.72]). Inheritance analysis revealed that TG + GG was correlated with the increased risk of SLE disease in the dominant model (OR=3.928; 95%CI [2.056, 7.74]). Moreover, subjects with the G allele were more frequently affected with SLE than individuals with the T allele (OR= 3.55; 95%CI [2.37, 5.36]). The G allele in patients was correlated with serum concentration of CRP, ESR, anti-dsDNA antibody, C3, and C4 and presentation of some clinical manifestations such as kidney involvements and skin lesions (P<0.05). Conclusion: Our findings suggest a substantial association between rs6445975 polymorphism in the PXK gene with susceptibility and clinical characteristics of SLE in the Iranian population.

Evaluation of Diagnostic Accuracy of Alpha-Fodrin Antibody in Iranian Patients with Sjogren's Disease.

Background: Sjogren's syndrome, as a chronic autoimmune disease, involves in lymphocytic infiltration in the exocrine glands. As the result of exocrine glands disruption, the clinical hallmark of this disease including dryness of mouth and eyes along with fatigue and joint pain occur. However, heterogeneity of clinical presentations among newly diagnosed adult patients with Sjogren's syndrome leads to difficulty in its diagnosis. One of the diagnostic criteria for Sjogren's syndrome is the presence of autoantibodies in patient serum. One of the novel biomarkers suggested for diagnosis of Sjogren is alpha-fodrin antibody. In this study, we aimed to evaluate the diagnostic power of anti-α-fodrin antibody among the Iranian population for the first time. Materials and Methods: We recruited 82 individuals in this study. Alpha-fodrin were measured in case and control with Elisa kit as 16.71 (9.84) and 18.44 (11.54). Results: There was no any significant difference between two groups regarding alpha-fodrin level (P = 0.35). Then we applied the receiver operating characteristic (ROC) curve analysis to determine the predictive value of alpha-fodrin for diagnosing Sjogren's disease. The area under curve of the ROC curve was calculated as 0.5453. Also, there were significant association between age and alpha-fodrin antibody. Conclusions: Alpha-fodrin test did not have acceptable predictive power for predicting Sjogren's disease; however, it could be associated with disease progression.

Assessment of Treatment Safety and Quality of Life in Patients Receiving Etanercept Biosimilar for Autoimmune Arthritis (ASQA): A Multicenter Post-marketing Surveillance Study.

INTRODUCTION: Phase IV post-marketing surveillance studies are needed to evaluate the real-world safety and effectiveness of drug products. This study aimed to evaluate the safety and effectiveness of biosimilar etanercept (Altebrel, AryoGen Co., Iran) in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA). METHODS: In this open-label, multicenter, prospective, observational, post-marketing surveillance study, 583 patients received biosimilar etanercept 25 mg twice weekly or 50 mg once weekly and were followed up to 12 months. The primary objective was to evaluate the safety of biosimilar etanercept by documenting all the adverse events in the case report forms throughout the study period. The secondary objective was to evaluate the effectiveness of biosimilar etanercept in study patients, where longitudinal changes in health assessment questionnaire (HAQ), pain, and disease activity scores were assessed. RESULTS: A total of 583 patients (44.80 ± 13.09 years of age) were included and followed for an average of 8.12 ± 3.96 months. Among all patients, 172 (29.50%) experienced at least one adverse event, and injection site reaction, abdominal pain, and upper respiratory tract infection were the most common. HAQ scores decreased from 1.32 ± 0.77 at baseline to 0.81 ± 0.61 at 12 months in patients with RA/PsA (p < 0.01) and from 0.82 ± 0.58 at baseline to 0.66 ± 0.63 at 12 months in patients with AS (p = 0.18). Pain scores decreased from 6.49 ± 2.41 at baseline to 3.51 ± 2.39 at 12 months (p < 0.01). CONCLUSION: The results demonstrated the real-world safety and effectiveness of biosimilar etanercept in patients with RA, PsA, and AS. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04582084.

Interferon-induced protein 44-like gene promoter is differentially methylated in peripheral blood mononuclear cells of systemic lupus erythematosus patients.

BACKGROUND: The objectives of this study were to compare the interferon-induced protein 44-like (IFI44L) promoter methylation level between systemic lupus erythematosus (SLE) patients and healthy controls and to evaluate its diagnostic value in SLE. MATERIALS AND METHODS: The IFI44L promoter methylation level was measured in 49 patients with SLE and 50 healthy controls. Quantitative analysis of promoter methylation IFI44L gene in genomic DNA samples extracted from peripheral blood mononuclear cells was examined in SLE patients and healthy controls. The level of DNA methylation was compared between SLE patients and healthy controls as well as within SLE patient groups based on the presence of renal involvement. Moreover, diagnostic values of IFI44L were calculated. RESULTS: The IFI44L promoter methylation level in SLE patients was significantly lower than healthy controls (median, 43.8 vs. 57, respectively; P = 0.008). The level of IFI44L promoter methylation was not significantly different between SLE patients with renal involvement and SLE patients without renal involvement (84.6% vs. 92.7%, respectively; P = 0.774). The IFI44L promoter methylation level ≤94.3% was the best cutoff point with a sensitivity of 91.8% and a specificity of 38% to distinguish patients with SLE from healthy individuals. CONCLUSION: The level of IFI44L promoter methylation from whole peripheral blood in Iranian SLE patients was significantly lower than healthy controls. Furthermore, the DNA methylation level of IFI44L promoter was not associated with renal damage in patients with SLE.

Ultrasonographic findings of rheumatoid arthritis patients who are in clinical remission.

BACKGROUND: The aim of this study was to recognize the findings of ultrasonography (US) in remitted rheumatic arthritis (RA) patients for detection subclinical arthritis. MATERIALS AND METHODS: This descriptive study was conducted during 2016 in a rheumatology center. A total of 70 patients with remitted RA were included in the study. Sonography was performed on all 70 patients who did not show any clinical arthritis in clinical examination to find synovitis and effusion were evaluated with gray scale and hyperemia with power Doppler US. RESULTS: Nearly 44.3% (n = 31) of our patients had positive sonography results including 20% synovitis, 21.4% hyperemia, and 18.6% (n = 13) effusion. A total of 1960 joints of 70 patients were evaluated, in which 3.2% (n = 63) of joints had positive sonography findings including 1.2% synovitis, 1.5% hyperemia, and 1.1 with effusion. CONCLUSION: US can diagnosis subclinical arthritis in patients with remitted RA who does not show any joint involvement in clinical examination.

The effect of Vitamin D supplementation in disease activity of systemic lupus erythematosus patients with Vitamin D deficiency: A randomized clinical trial.

BACKGROUND: The aim of this study was to check the effectiveness of Vitamin D supplementation on the disease activity of Vitamin D-deficient systemic lupus erythematosus (SLE) patients. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled trial, 45 Vitamin D-deficient SLE patients were studied in two groups, namely interventional and placebo groups. The interventional group patients were treated with Vitamin D (50,000 unit/weekly Vitamin D for 12 weeks and then 50,000 unit/monthly for 3 months) and placebo group patients were only administered the placebo. The level of Vitamin D and the level of disease activity using SLE disease activity index (SLEDAI) were measured before and after intervention period in each group, and for intra- and between-groups comparison, we used t-test and repeated measure ANOVA. RESULTS: A total of 90 patients were enrolled in this study. The mean of Vitamin D was increased significantly after therapy in interventional group (17.36 ± 4.26 ng/ml vs. 37.69 ± 5.92 ng/ml, P < 0.001). The mean of Vitamin D had no significant difference before and after intervention in placebo group (16.78 ± 4.39 ng/ml vs. 16.62 ± 4.61 ng/ml, P = 0.53). The mean of disease activity (SLEDAI) was not different significantly before and after Vitamin D administration in interventional group (3.09 vs. 1.62 ± 1.25, P = 0.39). The mean of disease activity (SLEDAI) was not different significantly before and after intervention in placebo group (3.09 vs. 1.98 ± 2.47, P = 0.42). CONCLUSION: According to our study, it is suggested that using Vitamin D in patients with SLE could not have better outcomes in this regard. However, there are many unknown environmental or biological factors which are associated with the disease activity of SLE and have not been identified yet.

Intravenous pamidronate for refractory rheumatoid arthritis.

BACKGROUND: Patients with rheumatoid arthritis may be resistant to conventional treatment with disease-modifying antirheumatic drugs (DMARDs). On the other hand, biologic therapy is costly and may be inconvenient for many patients. Pamidronate is a potent bisphosphonate with the capacity of modifying the biological activity of the immune system cells. It may thus be used as an anti-inflammatory agent in patients with inflammatory joint diseases. MATERIALS AND METHODS: To assess the effectiveness of pamidronate in the management of rheumatoid arthritis, we selected 38 patients with rheumatoid arthritis to enroll in a pilot study to receive pamidronate and conventional treatment with prednisolone and DMARDs in combination. These patients received 60 mg of pamidronate for 3 consecutive months and were followed for 6 months since the first infusion. RESULTS: The mean visual analogue score (VAS) and disease activity score (DAS28) fell steadily until one month after the third infusion. However, no improvements were observed during the 3 months after the last infusion of the drug. All patients, except one, reported decreased pain in response to 3 consecutive pulses of pamidronate and most had improvements in the assessed laboratory and clinical indices. The drug was tolerated well in our patients. CONCLUSION: Pamidronate infusions had beneficial effects on various clinical and laboratory parameters of patients, but alleviation of symptoms were temporary and did not last for more than 6 months. This treatment option can be a choice for difficult cases of rheumatoid arthritis with severe pain and osteoporosis.

The prevalence of musculoskeletal complaints in a rural area in Iran: a WHO-ILAR COPCORD study (stage 1, rural study) in Iran.

The objective of this study is to study the prevalence of musculoskeletal complaints and disorders in a rural area in Iran. Interviews were conducted in randomly selected subjects from five villages in Tuyserkan County, northwestern part of Iran. The three phases of stage 1 Community Oriented Program for Control of Rheumatic Diseases were done during the same day. A total of 614 houses was visited, 1,565 persons interviewed, and 1,192 persons examined. Musculoskeletal complaints during the past 7 days were detected in 66.6% (shoulder 22.7%, wrist 17.4%, hands and fingers 14.9%, hip 13.9%, knee 39.2%, ankle 19.6%, toes 12.7%, cervical spine 17.9%, and dorsolumbar spine 41.9%). Degenerative joint diseases were detected in 20.5% (cervical spondylosis 2.2%, knee osteoarthritis [OA] 19.3%, hand OA 2.7%, and hip OA 0.13). Low back pain was detected in 23.4%, soft tissue rheumatism in 2.2%, rheumatoid arthritis in 0.19%, ankylosing spondylitis in 1.1%, systemic lupus erythematosus in 0.06%, and fibromyalgia in 0.06%. The prevalence of rheumatic complaints in rural Iran is very high and needs attention in the curricula of medical schools and in the planning of rural health care by the government.