Association of the HLA-G gene +3142C>G polymorphism with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease that affects several organs and systems. Its etiology remains unknown, although it is probably multifactorial. The human leukocyte antigen G (HLA-G) is a nonclassic major histocompatibility complex I molecule characterized by restricted expression and low DNA polymorphism. HLA-G plays a role in immunosuppression through different mechanisms. In inflammatory diseases, it has been postulated that HLA-G expression may be a possible mechanism of tissue protection against exacerbated inflammatory response. On the 3' untranslated region (3' UTR) of the HLA-G gene, there is an insertion/deletion polymorphism of 14 bp (rs1704) that was shown to influence the mRNA stability. The influence of this polymorphism in disease susceptibility is controversial. Also in the 3' UTR there is a single nucleotide polymorphism C/G (rs1063320) on the position +3142, at a possible binding site for microRNAs (miRNAs) and having an influence on miRNA affinity. In this study, we analyzed the +3142C>G and the 14 bp polymorphisms in 195 SLE European-derived female patients. Our findings show a significant increase of the +3142G allele frequency among patients as compared with controls (0.58 vs 0.47, P = 0.011). Also, patients presented a higher frequency of the GG genotype (OR = 1.90, 95% CI: 1.08-3.42). Double heterozygotes for the two polymorphisms presented a milder mean systemic lupus erythematosus disease activity index (SLEDAI) than heterozygotes for only one of the variants or non-heterozygous individuals (1.56 vs 3.15 and 3.26, respectively, corrected P = 0.044). These results suggest the involvement of the HLA-G molecule on SLE susceptibility and outcome.     

Treating psoriatic arthritis to target: discordance between physicians and patients’ assessment,non-adherence,and restricted access to drugs precluded therapy escalation in a real-world cohort

Clinical Rheumatology - The treat-to-target strategy (T2T) was associated with better outcomes in psoriatic arthritis (PsA) compared to standard care in clinical trials. This study aimed to analyze...     

Effect of inflammatory activity and glucocorticoid [corrected] use on nutritional variables in patients with juvenile idiopathic arthritis

OBJECTIVE: To assess nutritional status in patients with juvenile idiopathic arthritis (JIA) and the influence of inflammatory activity and glucocorticoid use. METHODS: One hundred sixteen patients were evaluated. Disease subtype and disease activity were defined by the attending physician, and the cumulative glucocorticoid dose was recorded from chart review. Percentiles of body mass index (BMI) and triceps skinfold (TSF) and the Z score for height were determined: low weight and low adiposity were diagnosed when BMI and TSF were below the 5th percentile. Short stature was defined by a Z score of height for age < -2. Serum concentration of insulin-like growth factor-I (IGF-I) was measured by radioimmunoassay. RESULTS: The prevalences of low weight, low adiposity, and short stature were 16.4%, 20.7%, and 10.4%, respectively. Low IGF-I serum level was found in 14 patients (12.1%). The factors negatively associated with the Z score of height in multivariable regression analysis were disease duration (partial correlation coefficient -0.370, 95% confidence interval: -0.527 to -0.188; p < 0.001), erythrocyte sedimentation rate (ESR) (-0.357, -0.516 to -0.174; p < 0.001), and polyarticular or systemic disease subtype (-0.290, -0.459 to -0.100; p = 0.003), while there was no significant correlation with the cumulative dose of glucocorticoids (0.086, -0.111 to 0.277; p = 0.391). None of these variables was significantly correlated with the percentiles of BMI and TSF, albeit confidence intervals for these correlation coefficients were relatively large. Patients with a systemic or polyarticular disease subtype tended to present lower percentiles of BMI (p = 0.051). CONCLUSION: Nutritional status is frequently compromised in patients with JIA. Duration and disease subtype and the ESR are factors independently associated with short stature. The cumulative dose of glucocorticoids was not independently associated with short stature or with other nutritional variables, although a relevant negative effect of glucocorticoid dose on BMI and TSF cannot be entirely excluded.     

GSTT1, GSTM1 and GSTP1 polymorphisms and susceptibility to juvenile idiopathic arthritis

OBJECTIVE: In this study we have analyzed GSTM1, GSTT1 and GSTP1 polymorphisms in patients with juvenile idiopathic arthritis (JIA), to investigate a possible role of these genes as genetic components of the disease. METHODS: A total of 103 individuals (49 oligoarticular, 41 polyarticular and 13 systemic) were analyzed for the three polymorphisms, using a PCR/RFLP methodology. RESULTS: We have observed significantly increased frequencies of individuals with GSTT1 null genotype in JIA patients comparing to controls (37% x 21%; p=0.0183). There was a 2-fold increased risk (OR 2.2, 95% CI 1.2-4.1) associating the disease with the GSTT1 null genotype. Considering the subgroups (oligoarticular, polyarticular and systemic), the results indicated an association between polyarticular and systemic patients and the GSTT1 null genotype. There was a 2-fold increased risk for polyarticular patients (OR 2.4, 95%, CI 1.1-5.4), and a 4-fold increased risk for systemic patients (OR 4.4, 95%, 1.3-14.5). CONCLUSION: The GSTT1 null genotype seems to be involved in polyarticular and systemic JIA.     

The role of BsmI and FokI vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D in Brazilian patients with systemic lupus erythematosus

Vitamin D deficiency has been described in systemic lupus erythematosus (SLE). BsmI VDR (vitamin D receptor) gene polymorphism was associated with SLE in Asian patients. Studies in Brazilian populations have not been realized. A case-control study with 195 SLE patients and 201 healthy controls was conducted to investigate the influence of BsmI and FokI VDR gene polymorphisms on susceptibility to SLE. In addition, 25-hydroxyvitamin D [25(OH)D] was measured in SLE patients to evaluate possible associations with VDR polymorphic variants and clinical and laboratory expressions of disease. Genotyping was performed by RFLP-PCR. The measurement of 25(OH)D was performed by chemiluminescence. There was no statistically significant difference in genotype and allelic frequencies of BsmI and FokI polymorphisms between European-derived cases and controls. The mean serum levels of 25(OH)D were 25.51?±?11.43?ng/ml in SLE patients. According to genotype distribution, 25(OH)D concentrations were significantly higher in patients carrying the FokI f/f genotype compared with patients carrying the F/F genotype (31.6?±?14.1?ng/ml versus 23.0?±?9.2?ng/ml, p?=?0.004), reinforcing its role in the functional activity of VDR. This feature may be considered in future clinical and experimental studies involving vitamin D measurements. Therefore, genetic-specific definitions of ideal levels of vitamin D in SLE need to be established in future studies.     

Cachexia in patients with rheumatoid arthritis: a cohort study

Clinical Rheumatology - Rheumatoid arthritis (RA) is an inflammatory disease that leads to altered body composition. The loss of lean mass with a preservation or increase in fat mass has been...     

Association of concomitant fibromyalgia with worse disease activity score in 28 joints,health assessment questionnaire,and short form 36 scores in patients with rheumatoid arthritis

Objective

To study the association of the presence of fibromyalgia (FM) with the Disease Activity Score in 28 joints (DAS28), the Health Assessment Questionnaire (HAQ), and the Medical Outcomes Study Short Form 36 (SF‐36) health survey in patients with rheumatoid arthritis (RA).

Methods

A total of 270 outpatients with RA were enrolled in a prospective cross‐sectional study. The patients underwent clinical evaluation and application of the HAQ and SF‐36 questionnaires. Disease activity was evaluated using the DAS28 score. FM and RA diagnoses were made according to American College of Rheumatology criteria.

Results

The overall prevalence of FM was 13.4%. This group of patients had a higher prevalence of female sex, older mean age, higher functional class, and longer morning stiffness than patients with only RA. Mean ± SD DAS28 scores were significantly higher in patients with RA and FM (5.36 ± 0.99) than in patients with RA only (4.03 ± 1.39; P < 0.001). In a multivariable linear regression analysis, FM was an important predictor of the DAS28 score, even after adjusting for the erythrocyte sedimentation rate, number of swollen joints, functional class, number of disease‐modifying antirheumatic drugs currently in use, current dose of steroids, and articular erosions. HAQ and SF‐36 scores were also worse in patients with RA and associated FM.

Conclusion

FM is related to worse scores on the DAS28, HAQ, and SF‐36 in patients with RA. The presence of FM may have major implications in the interpretation of the DAS28 score because it is related to higher scores independently of objective evidence of RA activity.