Correlations and Influence of TAP2 Genes Polymorphisms and Systemic Lupus Erythematosus Propensity.

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.

Helicobacter Pylori Infection in Sjögren's Syndrome: Co-incidence or Causality?

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.

In vitro modulatory effect of dehydroepiandrosterone sulfate on apoptosis and expression of apoptosis-related genes in patients with systemic lupus erythematosus.

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.

Protective role of HLA-DRB1*11 against juvenile idiopathic arthritis living in North Eastern Iran.

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.

Superiority of laterally elevated wedged insoles to neutrally wedged insoles in medial knee osteoarthritis symptom relief.

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.

Stronger Correlation between Interleukin 18 and Soluble Fas in Lupus Nephritis Compared with Mild Lupus.

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.

Bone-related complications of transfusion-dependent beta thalassemia among children and adolescents.

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.

The pathway of estradiol-induced apoptosis in patients with systemic lupus erythematosus.

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-ß 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.

Microembolic signals in patients with systemic lupus erythematosus.

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.

Correlation between serum levels of soluble Fas (CD95/Apo-1) with disease activity in systemic lupus erythematosus patients in Khorasan, Iran.

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.

Hearing loss in Behçet syndrome.

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.

Sex hormones and peripheral white blood cell subsets in systemic lupus erythematosus patients.

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.