Association of the STAT4 Gene rs7574865 Polymorphism with IFN-γ Levels in Patients with Systemic Lupus Erythematosus.

STAT4 plays an important role in disease activity in SLE patients. STAT4 particles have the capacity to activate the transcription of genes associated with the production of TH1 and Th17 lymphocytes, with a greater predominance on the production of IFN-γ and IL-17A. The presence of variants in STAT4 genes has a major impact on the generation of autoimmunity. However, there are few studies evaluating the impact of these variants on the production of proinflammatory cytokines such as IFN-γ and IL-17A. Methods-A case-control study was carried out with 206 Mexican mestizo patients residing in Western Mexico with a diagnosis of SLE and a group of 80 patients without autoimmune diseases was captured to determine the cut-off point for high IFN-γ levels. In this study, SLE patients with high IFN-γ levels were considered as cases (cut-off > 15.6 pg/mL), and SLE patients with normal IFN-γ levels were considered as controls (cut-off ≤ 15.6 pg/mL). Disease activity was identified from the systemic lupus erythematosus disease activity index (SLEDAI). For the determination of levels of cytokines IFN-γ, IL-12, and IL17A, commercial ELISA kits were used. Genotyping of STAT4 rs7574865 (G > T) was performed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. Results-The patients with SLE had a median age of 45 years with a range of disease duration from 4 years to 18 years; 45.6% were identified as having disease activity. In this sample, we identified a high IFN-γ prevalence of 35.4%. The levels of IFN-γ were higher in the patients with genotype TT than GG. We found that TT genotype conferred a higher risk of high IFN-γ when compared to the GG and GT genotypes. Conclusions-In this study, we identified that the polymorphic genotype TT of the STAT4 gene rs7574865 polymorphism is associated with increased levels of IFN-γ. However, its strength of association was weak, so complementary studies are needed to evaluate its impact on SLE patients.

Functional disability is related to serum chemerin levels in rheumatoid arthritis.

Adipokines, especially chemerin, can interact with cytokines and other molecules in inflammation. To date, there is insufficient information regarding a possible correlation between functional disability and chemerin and other pro-inflammatory molecules in rheumatoid arthritis (RA). To identify the association of functional disability with serum chemerin and other pro-inflammatory molecules, including other adipokines, cytokines and E-selectin, in patients with RA. Cross-sectional study. Assessment: disease activity (DAS28-ESR) and functional disability (HAQ-DI). We compared the adipokines (chemerin, leptin, adiponectin, resistin, and visfatin), cytokines (TNF-α, IL-6, IL-1ß, and IL-18) and E-selectin levels between RA with functional disability and RA non-disabled patients. Of 82 patients with RA, 43 (52%) had functional disability. The RA with functional disability group had higher chemerin (140 vs. 112 ng/mL, p = 0.007) than the non-disabled RA group. Chemerin correlated with the HAQ-DI (rho = 0.27, p = 0.02) and DAS28-ESR (rho = 0.21, p = 0.05). Severe activity correlated with IL-6 (rho = 0.33, p = 0.003) and E-selectin (rho = 0.23, p = 0.03) but not with disability. No other pro-inflammatory molecules correlated with HAQ-DI. High chemerin levels were associated with functional disability in RA, whereas no other molecules correlated with loss of function. These results encourage further studies assessing new roles of chemerin as a marker of impairment in RA.

Association of myostatin, a cytokine released by muscle, with inflammation in rheumatoid arthritis: A cross-sectional study.

ABSTRACT: Myostatin is a cytokine produced and released by myocytes that might have an outstanding role not only in muscle wasting during cachexia but also in inflammation. Herein we explore the association between myostatin levels and inflammatory parameters in rheumatoid arthritis (RA).One hundred twenty-seven women without rheumatic diseases and 84 women with a diagnosis of RA were assessed in a cross-sectional study. Outcomes reflecting the activity of the arthritis including Disease Activity Score (DAS28-ESR) and impairment in functioning by the Health Assessment Questionnaire-Disability Index were assessed in RA. We obtained Skeletal muscle mass index (SMI), fat-free mass index (FFMI), and fat mass index using dual-energy x-ray absorptiometry. Serum myostatin was determined by enzyme-linked immunosorbent assay. Myostatin levels were correlated with disease activity and parameters of muscle mass.The SMI was lower and concentration of myostatin was higher in RA patients than in controls (P = .008 and P < .001, respectively). Myostatin significantly positively correlated with C-reactive protein (rho = 0.48, P < .001), erythrocyte sedimentation rate (rho  = 0.28, P = .009), and DAS28-ESR (rho = 0.22, P  = .04), and negatively correlated with SMI (rho = -0.29, P = .008), (FFMI) (rho = -0.24, P = .027). In the multivariate logistic regression analysis, levels of myostatin remained associated with disease activity in RA (P = .027).In our study, myostatin was associated with disease activity in RA patients, suggesting a mechanistic link between myostatin, muscle wasting and inflammation in RA.

Fasting triglycerides and glucose index: a useful screening test for assessing insulin resistance in patients diagnosed with rheumatoid arthritis and systemic lupus erythematosus.

BACKGROUND: Insulin resistance (IR) is frequently observed in patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). In clinical practice, IR assessment is limited to a low proportion of patients due to cost and equipment and technical expertise requirements. The surrogate index of triglycerides and glucose (TyG index) has been validated in non-rheumatic populations, showing adequate sensitivity and specificity for IR, although this index has not yet been used in connective tissue disorders. The aim of this study was to evaluate the frequency of insulin resistance (IR) using the validated surrogate index of triglycerides and glucose (TyG index) and to explore factors associated with IR in Mexican women with RA or SLE. METHODS: Ninety-five female RA and 57 SLE patients were included in a cross-sectional study. Clinical and epidemiological variables were evaluated. IR was assessed using the TyG index with a cutoff value of > 4.68. Logistic regression analysis was performed to identify factors associated with IR excluding confounders. RESULTS: IR frequency in the entire sample was 50%, higher than the 10% observed in non-rheumatic controls (p < 0.001). The frequency of IR was similar in SLE (49.1%) and RA (50.5%, p = 0.8) patients. IR was associated with a longer duration of hypertension and higher total cholesterol and low density lipoprotein cholesterol levels. Based on multivariate analysis, the duration of hypertension (OR: 1.06; 95% CI 1.002-1.12, p = 0.04), waist circumference (OR: 1.04; 95% CI 1.01-1.08, p = 0.007), uric acid levels (OR: 1.46; 95% CI 1.08-1.97, p = 0.01), RA (OR: 4.87; 95% CI 1.31-18.78, p = 0.01) and SLE (OR: 4.22; 95% CI 1.06-16.74, p = 0.04) were the main risk factors for IR. CONCLUSIONS: This study shows that the TyG index is a useful screening test for IR in RA and SLE patients. Future longitudinal studies should be performed with the aim of identifying the predictive value of TyG index results for identifying complications linked to IR.

Serum levels of P-glycoprotein and persistence of disease activity despite treatment in patients with systemic lupus erythematosus.

Around 25% of patients with systemic lupus erythematosus (SLE) could be refractory to conventional therapies. P-glycoprotein expression on cell surface has been implied on drug resistance, however, to date, it is unknown if P-gp serum levels are associated with SLE disease activity. Evaluate the association of serum P-gp levels and SLE with disease activity despite treatment. A cross-sectional study was conducted on 93 female SLE patients, all receiving glucocorticoids at stable doses for the previous 6 months before to baseline. SLE patients were classified into two groups: (a) patients with active disease [SLE disease activity index (SLEDAI) ≥ 3] despite treatment, and (b) patients with inactive disease (SLEDAI < 3) after treatment. Forty-three healthy females comprised the control group. Serum P-gp, anti-DNA, and both anti-nucleosome antibody levels were measured using ELISA. Active-SLE patients despite treatment had higher P-gp levels compared with inactive-SLE after treatment (78.02 ng/mL ± 114.11 vs. 33.75 ng/mL ± 41.11; p = 0.018) or versus reference group subjects (30.56 ng/mL ± 28.92; p = 0.011). P-gp levels correlated with the scores of SLEDAI (r = 0.26; p = 0.01), Mexican-SLEDAI (MEX-SLEDAI) (r = 0.32; p = 0.002), SLICC/ACR damage index (r = 0.47; p < 0.001), and with prednisone doses (r = 0.33; p = 0.001). In the multivariate model, the high P-gp levels were associated with SLICC/ACR score (p = 0.001), and SLEDAI score (p = 0.014). Our findings support a relationship between serum P-gp levels and SLE with disease activity despite treatment, but it requires further validation in longitudinal studies.

[Assessment of the ability of first contact physicians in the treatment of rheumatoid arthritis]. / Evaluación de la competencia para el tratamiento de la artritis reumatoide por médicos de primer contacto.

Rheumatic Diseases (RD) are part of the 20 most frequent reasons for consultation in family medicine, therefore, it is mandatory that family physicians perform an opportune recognizement and therapeutic approach of RD. The aim of this study was to measure the clinical competence for identification and therapeutic approach of rheumatoid arthritis (RA) of 144 from 450 family physicians by using a structured and validated instrument. The FP Sample was obtain from 5 randomly selected from 23 Family Medicine Units of the Instituto Mexicano del Seguro Social in the city of Guadalajara, Mexico. Main outcome measure was the clinical competence of FP, defined as the capacity to interpretate, to evaluate and proposals realized in its clinical practice. Competence levels were expressed in an ordinal scale and its association with other variables was assessed by using Kruskal-Wallis test or Chi square test. Clinical competence median value was 47.3, ranking from -6 to 90, and no statistical difference was found when comparing by Family Medicine Unit, neither when comparing by other variables. We conclude that 15.3 % of FP met clinical competence for identification and therapeutic approach of rheumatoid arthritis (RA).