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Objectives: The present study was designed to evaluate the association of transporters associated with antigen processing (TAP2) polymorphisms TAP2-379Ile > Val (rs1800454), TAP2-665Thr > Ala (rs241447) and TAP2-565Ala > Thr (rs2228396) as a candidate gene with susceptibility to the Systemic Lupus Erythematosus (SLE)., Methods: To analyze these three polymorphic variants, 88 patients with SLE and 100 healthy controls from northeastern Iran were enrolled from May 2018 to July 2019. Genomic DNA polymorphisms were performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. Data were analyzed by SPSS software., Results: In this cross-sectional study, there was a stratification between patients and controls. The distribution of the frequency of Ala73 (41.5%) allele at TAP2/665 and Ile 19 (10.8%) allele at TAP2/379 was higher in patients. Additionally, the Ala/Ala 13(14.8%) and Ala/Thr 49(55.7%) genotypes distributions at 665 positions were higher in SLE patients compared to the controls. Furthermore, frequencies of TAP2*H allele significantly increased in SLE patients 10(5.71%) (P=0.01). Frequency of TAP2*A allele in the control group was 120(60%) (p=0.06) due to the dominant genetic model. This allele has a protective effect against SLE. There was no relationship between TAP2*D, TAP2*E, TAP2*F and TAP2*G alleles with the outbreak of SLE., Conclusion: Our data indicated that genetic variants in TAP2 gene may be associated with SLE disease. A correlation between Ala allele at TAP2/665 and Ile allele at TAP2/379 polymorphisms and pathogenesis of SLE was observed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Interleukin (IL)-1 has a major role in cell destruction and inflammation. IL-1 receptor antagonist (IL-1RN or IL-1Ra) is a natural anti-inflammatory molecule that blocks IL-1. We intended to determine whether IL-1RN or IL-1Ra variable number tandem repeat (VNTR) polymorphism is associated with susceptibility to systemic lupus erythematosus (SLE) in a series of patients in the Northeastern part of Iran., Methods: Genomic DNA was extracted from the whole blood of 104 SLE patients and 209 subjects without SLE as a control group. The control group was matched for age and gender with SLE patients. Then, genomic DNA was genotyped by polymerase chain reaction (PCR) method for a length polymorphism in intron 2 of the IL-1RN gene., Results: Of five alleles, only allele 4 of IL-1RN had a higher frequency in healthy subjects (2.4%) compared to SLE patients (0), with a statistically significant difference (P= 0.03). Eleven kinds of polymorphisms of IL-1RN were found including 1/1, 1/2, 2/2, 3/3, 1/3, 3/5, 2/3, 2/5, 1/5, 4/4 and 1/4 in both groups. In genotype frequency, there was no statistically significant difference regarding gene polymorphism kinds between the two groups (P= 0.29)., Conclusion: Alleles 4 of IL-1RN may have a protective role against SLE susceptibility. However, SLE was not associated with any of the 11 kinds of genotype IL1-RN gene polymorphisms studied here., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Systemic lupus erythematosus‌ (SLE) is an autoimmune disease characterized by hyperactive B cells that produce various autoantibodies. Sex hormones have been documented to influence the development of SLE, in which women with SLE have low plasma level of dehydroepiandrosterone sulfate (DHEAS). A strong conclusion about the effect of DHEAS on apoptosis in SLE patients has not been provided. The aim of this study was to assess apoptotic effects of DHEAS on peripheral blood lymphocytes (PBLs) from SLE patients., Methods: Twenty SLE patients and 20 age- and sex-matched healthy controls were included into this study. Concentration of DHEAS was measured using enzyme-linked immunosorbent assay in serum from all participants. Freshly isolated PBLs from each individual were treated with 7.5-µmol of DHEAS for 24 hr in cell culture medium to assess the effect of DHEAS on apoptosis using fluorescein isothiocyante-conjugated annexin V and propidium iodide. The messenger RNA (mRNA) expression level of apoptosis-related genes (Fas, Fas-L, Bcl-2, and Bax) in PBLs was measured using real-time PCR before and after treating with DHEAS., Results: Level of DHEAS was low in SLE patients compared with healthy controls (p < 0.05). After treating with DHEAS, the percentage of apoptotic cells in SLE patients was decreased in comparison with healthy controls. DHEAS treatment increased the mRNA expression level of Bcl-2 in PBLs from SLE patients., Conclusions: DHEAS reduced the apoptosis rate in PBLs from SLE patients and may decrease the load of autoantigens. Therefore, DHEAS might be considered as a therapeutic tool in SLE patients., (© 2018 Wiley Periodicals, Inc.)

Background and Aim: Lymphoid cell infiltration and destruction of exocrine glands, specifically lacrimal and salivary glands are characteristics of Sjogren's syndrome (SS). An etiological role has been proposed for Helicobacter pylori (H. pylori), interacting in the clinical course and complications of SS (including gastric cancer and lymphoma). The aim of this study was to identify the probable correlation between H. pylori infection and Sjogren's syndrome (SS)., Methods: In this case-control study, ELISA method was used to determine serum level of IgA and IgM anti H. pylori antibody in 43 subjects with SS according to the international criteria and 95 healthy subjects as control. SPSS-17 was used to analyze data with t-test. P value <0.05 were considered significant., Results: Serum level of IgM (34.9% vs. 10.5%, p-value= 0.001) and IgA (67.4% vs. 46.3% p value= 0.021) anti H. pylori antibody were significantly higher in SS patients compared to the control group. There was a positive correlation between age and H. pylori infection (r=0.2, Pvalue= 0.05)., Conclusion: Patients with SS had a higher prevalence of H. pylori infection compared to the normal population. Eradication of H. pylori is recommended particularly in older patients with SS., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Juvenile idiopathic arthritis (JIA) is one of the most common chronic rheumatic diseases in children. The complex nature of this immune-mediated disease owes itself to several predisposing genes and environmental factors affecting its pathogenesis. Conducted in Iran, this study was originally intended to investigate every possible association between HLA DRB1 alleles and a susceptibility to JIA., Materials and Methods: In this case-control study, 45 patients with a definite diagnosis of JIA based on International League against Rheumatism (ILAR) criteria were compared against 46 healthy controls. DNA samples taken from both groups were analyzed using PCR-sequence specific primers (PCR-SSP) method. Data analysis including parametric and nonparametric test and multivariate analysis was undertaken using the SPSS 11.5 software. A P-value< 0.05 was regarded as statistically significant., Results: Mean ages in case group and healthy controls were 14.64±6.21 and 13.73±6.39, respectively with no significant difference between the two groups ( P =0.515). Sex difference between JIA group and healthy controls was also not significant ( P =0.068). The frequency of HLA-DRB1*01 was found the most frequent HLA-RB1 in our patients (33.3%). No significant statistical correlation between various HLA-DRB1 alleles and clinical subtypes of the disease could be established from the data. HLA-DRB1*11 was shown to raise protection to JIA ( P =0.035, OR=2.755, 95% CI=0.963-8.055) in northeastern Iran. In addition, we found that HLA-RB1*09 is nominally associated with an increased risk of JIA ( P =0.56, OR=2, 05, 95% CI=0.18-23.63)., Conclusion: HLA-DRB1*11 was shown to raise protection to JIA in northeastern Iran. The disparity of findings in other ethnicities prompts further investigations with larger sample sizes.

Aim: Knee osteoarthritis (OA), is the most common degenerative joint disease. Several non-pharmacological interventions have been used for this purpose such as insoles. There are contradictory data about the superiority and effectiveness of laterally wedged compared with neutrally wedged insoles. This study was designed to compare the effectiveness of laterally and neutrally wedged insoles in management of knee OA., Methods: In this double-blind, parallel treatment trial, 118 patients with knee OA according to American College of Rheumatology (ACR) criteria were enrolled and were followed for 2 months. Patients were randomly divided into two groups. Fifty-seven of them were treated with 5° laterally elevated wedged insoles (group A) and 61 patients were treated with neutrally wedged insoles (group B). Edinburg Knee Functional Scale (EKFS) was used to evaluate knee function before and after interventions. At the end of 2 months, severity of knee pain during the previous 2 days, numbers of non-steroid anti inflammatory drugs (NSAIDs) used for pain relief within the last 2 weeks and EKFS were assessed., Results: Severity of knee pain decreased in both groups after intervention. The mean difference in groups A (laterally wedged insole) and B (neutrally wedged insole) were 29.3 (95% confidence interval [95% CI]: 25.12, 33.55) and 6.25 (95% CI: 3.09, 9.4), respectively (P < 0.001 for both). In addition, at the end of the study, EKFS improved significantly in group A (mean: 7.54, 95% CI: 6.3, 8.8; P < 0.001), while in group B we could not find significant improvement (mean: 0.54, 95% CI: -0.41, 1.5; P = 0.166). Numbers of NSAIDs used during the two final weeks of the study significantly decreased compared with baseline in group A (P = 0.001; mean: 2.6, 95% CI: 1.3, 3.9); while in group B this was not shown (P = 0.9; mean: 0.05, 95% CI:-0.87, 0.97)., Conclusion: This study suggests that laterally elevated wedged insoles are more effective than neutrally wedged insoles, in pain relief of knee OA., (© 2013 The Authors International Journal of Rheumatic Diseases © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Thalassemia and the blood transfusion complications associated with it predispose children to poor bone health. This study was conducted to determine the prevalence of bone-related abnormalities and identify the bone health predictors within this population. One hundred and forty transfusion-dependent beta thalassemic subjects 8-18 years old in Mashhad, Iran, participated in this cross-sectional study. Anthropometric measures, dietary intake, bone-related biomarkers and bone densitometry, were assessed. The incidence of underweight and short stature was 33.6 and 41.4 %, respectively, which were indicators of malnutrition among thalassemic subjects in this study. Low bone density was detected in the lumbar spine and femoral region in 82 and 52 % of subjects, respectively. Hypocalcemia and hypophosphatemia were seen in 22 and 18.2 %, whilst vitamin D deficiency was present in more than 85 % of thalassemic children and adolescents. The relationships between weight, height and other anthropometric indices, serum calcium and bone markers, intake of macronutrients, zinc and vitamin E with bone mineral density (BMD) and bone mineral content (BMC) in the lumbar spine and femoral area were positively related, indicating that better nutritional status were associated with higher BMD and BMC values. Puberty, gender and serum osteocalcin were negative predictors for BMD and BMC values, whereas age, weight and height were the positive predictors. High incidence of low bone density and deficit in other aspects of bone health among thalassemia patients makes routine bone health assessment necessary for this vulnerable group. Considering influencing factors, dietary counseling and preventive supplementation therapy for this high risk group of children and adolescents may be necessary, although this should be assessed by intervention studies.

Lupus nephritis (LN) is a major cause of morbidity in patients with systemic lupus erythematosus (SLE). Several cytokines and apoptotic markers such as IL-18 and soluble Fas (sFas) have been assumed to play a role in the pathogenesis of LN. Previous studies confirmed that serum concentrations of sFas and IL-18 are increased in SLE. However, only a few studies have suggested a possible correlation between IL-18 and sFas. This study was planned to continue our previous study on the correlation between those markers to evaluate this correlation in LN. Thirty-two patients with only LN and 46 patients without any major organ involvement participated in this study. SLEDAI score (except for scores related to nephritis) was the same in these two groups. In both groups, patients with any other major organ involvement were excluded. We found a significant rise in the serum concentrations of sFas (P = 0.03) and IL-18 (P = 0.02) in patients with proteinuria compared to those without it. This study showed that the correlation between sFas and IL-18 in LN (P < 0.001, r p = 0.5) is significantly stronger than it is in mild SLE (P < 0.001, r p = 0.4) with similar nonrenal SLEDAI score (P = 0.032, z = 1.85). Between these two serum markers, sFas is the only predictor of proteinuria.

Systemic lupus erythematosus (SLE) is a disease with unknown etiology. The pathologic role of sex hormones and apoptosis in SLE has often been discussed. We studied the effects of estradiol in the pathway of induced apoptosis in Iranian SLE patients. T lymphocytes from 35 SLE patients and 20 age-matched controls were isolated and cultured in the presence of 10(-8) M 17-β estradiol. The expression levels of Fas, Fas ligand (FasL), Bcl-2, caspase-8, and caspase-9 mRNAs were determined semiquantitatively in comparison to the expression level of beta actin RNA. Estradiol exposure did not have any significant effects on the expression levels of Fas, Bcl-2, and caspase-9 in SLE patients and controls. However, the expression levels of FasL and caspase-8 were significantly increased in SLE patients, but not in controls. This suggests the probable involvement of extrinsic apoptosis pathway in estradiol-induced apoptosis in SLE.

The role of C-reactive protein (CRP) in systemic lupus erythematosus (SLE) as an inflammatory marker is still controversial. Recently, more sensitive methods, such as high sensitive CRP (hs-CRP) have been used to detect micro-inflammation. The role of hs-CRP in lupus flare has not been documented well. We conducted this study to examine the correlation between hs-CRP serum concentrations and disease activity in lupus. Ninety-two SLE patients and 49 healthy controls contributed to our study. Most confounding factors influencing the hs-CRP values were excluded. Disease activity was estimated using the SLE Disease Activity Index (SLEDAI-2K). hs-CRP values were determined using an enzyme-linked immunosorbent assay (ELISA) kit. Serum values of hs-CRP were significantly higher (p < 0.001, z = 3.29) in patients compared with healthy controls. The cutoff point for hs-CRP between patients and controls was 0.93 mg/L (Youden's Index = 0.39). There was no correlation between hs-CRP serum levels and disease activity. Furthermore, hs-CRP values did not correlate with any of the laboratory parameters, except for C3 (p = 0.003, r(s)  = -0.2) and C4 (p = 0.02, r(s) = -0.1). Although hs-CRP serum levels were significantly higher in lupus patients compared with healthy controls, it seems that this marker is not a good indicator for disease activity.

Rheumatoid arthritis (RA) is the most common form of autoimmune arthritis. Increased prevalence of metabolic syndrome (MetS) in RA may occur secondary to specific drug treatment and reduced physical activity associated with this condition. However, some recent studies suggest contradictory theories about the association of RA with MetS. This study was designed to evaluate the frequency of MetS in RA patients and the relationship between MetS with RA disease activity and body mass index (BMI). The study was conducted on 120 RA patients and 431 age- and sex-matched apparently healthy controls. A considerable proportion of patients were being treated with prednisolone and/or methotrexate and/or hydroxychloroquine. Disease activity was measured by the 28 joint count of disease activity score-Cerythrocyte sedimentation rate (DAS28ESR). MetS was evaluated according to International Diabetic Federation (IDF) and Adult Treatment Panel III (ATP III) criteria. The prevalence of MetS was significantly higher in the control group (p = 0.005). We did not find any difference in the prevalence of MetS between the patients with DAS < 3.2 and DAS ≥ 3.2. There was no association between the DAS28 score and the presence of MetS components by either definition. Multiple logistic regression analysis showed that the odds of a DAS > 3.2 in patients with BMI between 25 and 30 kg/m2 (OR = 0.1, p = 0.01) and BMI > 30 kg/m2 (OR = 0.3, p = 0.1), in comparison to BMI < 25 kg/m2, was 1/5 and 1/3, respectively. RA was not found to increase the risk of MetS. In addition, disease activity in RA patients was not influenced by the presence of MetS.

Knee osteoarthritis (OA) is a common degenerative joint disorder and a major cause of pain and disability. The hypothesis tested in this study was that the passion fruit peel extract (PFP), a flavonoid-rich dietary supplement, would reduce symptoms due to knee OA. Thirty-three OA patients were enrolled in a randomized, double-blind, placebo-controlled trial with parallel-group design. Patients received either placebo or PFP pills (150 mg, daily) in a double-blinded fashion for 2 months. The OA clinical symptoms were evaluated monthly with Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. In the PFP group, there was a significant improvement in total WOMAC score and WOMAC subscale score of physical function after 30 days and pain after 60 days. At 60 days, reductions of 18.6%, 18%, 19.6%, and 19.2% in pain, stiffness, physical function, and composite WOMAC score, respectively, were self-reported in the PFP group. Whereas, in the placebo group, the self-reported WOMAC scores increased in every category. The results of this study show that PFP substantially alleviated osteoarthritis symptoms. This beneficial effect of PFP may be due to its antioxidant and antiinflammatory properties., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Introduction: Central nervous system (CNS) involvement is a common and less understood aspect of systemic lupus erythematosus (SLE). Microembolic signals (MES) have been reported in SLE. We conducted a prospective study to evaluate the frequency of MES among patients with CNS involvement and those without. The main aim of the study is to clarify the pathophysiology of the CNS involvement in SLE., Methods and Materials: Sixty eight patients with a diagnosis of SLE (60 females, 8 males) participated in the study. Both middle cerebral arteries were monitored using transcranial Doppler for 60 min to detect MES. All cases underwent neurology and psychiatry assessments., Results: MES were detected in 7/68 patients (10.3%) with the mean number of 3.5 per hour. MES were significantly higher in patients with CNS involvement (6/24, 25%) than those without (1/44, 2.2%) (P=0.006). SLE disease activity index, duration of disease, plaque formation, intima-media thickness, and antiphospholipid antibodies were not associated with MES. MES were more frequent in patients receiving Aspirin and/or Warfarin (p=0.02)., Conclusions: MES may be a predictor for CNS involvement in SLE patients at risk for neuropsychiatric syndromes. Cerebral embolism may be implicated in the pathophysiology of neuropsychiatric SLE.

Objective: The aim of this cross-sectional analytic study was to evaluate the diagnostic efficacy of panoramic-based indices of the mandible (Mental Index-MI, Mandibular Cortical Index-MCI and Panoramic Mandibular Index-PMI) and to determine their correlation with bone mineral density (BMD) of the femoral neck and lumbar vertebrae (L2-L4) in order to assess the possibility of using these parameters as indicators of osteoporosis., Materials and Methods: The mandibular indices of 67 women over 35 years old were measured from panoramic radiographs, and bone densitometry was performed in the femoral neck and lumbar vertebrae (L2-L4), using DXA (Dual Energy X-ray Absorptiometry) technique. The patients were divided into three categories of normal, osteopenic and osteoporotic in each skeletal region. One-way ANOVA and ROC curve analyses were applied. The results were considered statistically significant when the P-value was less than 0.05., Results: Comparing the mean BMD in the femoral neck in women between C1 and C3 subgroups of MCI, a significant difference was detected (P=0.04). The mean PMI in the three skeletal subgroups was not different according to the skeletal region (P>0.05). We found a significant difference in mean MI between normal and osteopenic subgroups in the femoral neck (P=0.042)., Conclusion: Using radiomorphometric indices of the mandible (MCI-MI) may be useful in determining the skeletal status of the patients, but is not sufficient for precise evaluation.

Background: Soluble Fas (sFas) is a marker of apoptosis that appears to increase in the serum of systemic lupus erythematosus patients and may have a correlation with disease activity. The exact role of sFas in apoptosis is not clear. The purpose of this study is to assess the correlation between serum levels of soluble Fas (Apo/1-CD95) and the activity of systemic lupus erythematosus., Methods: Our study was performed on 114 systemic lupus erythematosus patients who were compared with 50 randomly selected sex, age and race-matched healthy controls. Disease activity was defined according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K). All physical exams and laboratory parameters were collected to determine the SLEDAI. sFas levels were determined using a commercially available ELISA kit., Results: There was a significant difference between serum levels of sFas in the case and control groups (P=0.001). A significant correlation coefficient existed between the sFas and SLEDAI2K variables (P=0.001, r=0.494). Significant statistical difference was found between serum levels of sFas in the active and inactive phases of disease according to SLEDAI< or =9 or > or =10, (P=0.002). The sFas levels were 270 - 300 pg/mL for SLEDAI< or =9 and 355-502 pg/mL for SLEDAI> or =10, with a confidence interval of 95 percent., Conclusion: This study shows a significant elevation of sFas levels in the sera of systemic lupus erythematosus patients with active disease; therefore it can be used as an appropriate marker for evaluation of disease activity.

Objective: To determine the prevalence and characteristics of hearing loss in Behçet syndrome., Study Design and Setting: This study included 27 patients with Behçet syndrome and 35 sex-and age-matched controls. A complete audiological evaluation was performed., Results: The average pure-tone audiograms from both groups showed a statistically significant hearing loss in the Behçet group. Sixteen patients (59.26%) showed some degrees of sensorineural hearing loss (SNHL), with the high-frequency type (4, 8, 10, and 12 kHz) being the most common pattern (93.75%). Hearing loss was the fourth most common manifestation. Although the patient's age, sex, and the duration of the disease were not related to hearing loss, there was a significant correlation between a negative pathergy test and hearing loss in patients with Behçet syndrome., Conclusion: We should consider audiovestibular involvement in Behçet syndrome as a common finding.

Background: Systemic Lupus Eyrythematosus (SLE) is an autoimmune disease characterized by antibodies to nuclear antigens, particularly anti-dsDNA. Imbalance between production and destruction of immune cells causes cytopenia. Sex hormones have immunomodulatory effects; estrogen increases the production of autoantibodies in SLE prone NZB/NZW mice., Objective: To investigate the relationship between sex hormones, anti-dsDNA, and lymphocyte subsets in Iranian patients with SLE., Methods: 38 SLE patients (28 females and 10 males) meeting 4 of 11 ACR revised criteria for SLE classification, and 20 age and sex matched healthy individuals (10 females and 10 males) participated in this study. Lymphocyte subsets were analyzed using flow cytometric analysis. Serum anti-dsDNA levels and sex hormones concentrations were determined using commercial ELISA and RIA kits, respectively., Results: The absolute count of white blood cells, lymphocytes, T lymphocytes (CD3+), T helper cells (CD3+CD4+), B cells (CD19+) and Nk cells (CD3- CD16+CD56+) in SLE patients diminished significantly in comparison to control group (p<0.05). IgG anti-dsDNA antibody levels were significantly higher in patients compared to controls as expected (p<0.05). Prolactin increased significantly, while DHEAS showed a significant decrease in SLE patients compared with the controls (p<0.05), however the level of estrogen did not have any significant difference in SLE patients in comparison to controls., Conclusion: Increased concentration of prolactin together with a simultaneous decrease in serum DHEAS in SLE patients are associated with anti-dsDNA elevation and a decrease in almost all lymphocyte subsets.