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.

Background. Myostatin is a regulator of muscle size. To date, there have been no published studies focusing on the relation between myostin levels and myopenia in rheumatoid arthritis (RA). Objective. Evaluate the value of serum myostatin as a biomarker of cachexia and low skeletal muscle mass (LSMM) in RA patients, along with whether high serum myostatin is associated to these conditions after adjusting for potential confounders. Methods. This cross-sectional study included 161 female RA patients and 72 female controls. In the RA group, we assessed several potential risk factors for LSMM and rheumatoid cachexia. Dual-energy X-ray absorptiometry was used to quantify the skeletal muscle mass index (SMMI) (considering kg/m²) and the presence of rheumatoid cachexia (a fat-free mass percentile and fat mass percentile of the reference population). Serum myostatin concentrations were determined by ELISA. To identify a cut-off for high serum myostatin levels, we performed ROC curve analysis. Multivariable logistic regression analysis was used to identify the risk factors for LSMM and rheumatoid cachexia. The risk was expressed as odds ratios (ORs) and their 95% confidence intervals (95% CIs). Results. Compared to the controls, the RA group had a higher proportion of LSMM and exhibited high serum myostatin levels ( ). ROC curve analysis showed that a myostatin ng/mL was the most efficient cut-off for identifying rheumatoid cachexia (sensitivity: 53%, specificity: 71%) and LSMM (sensitivity: 43%, specificity: 77%). In the multivariable logistic regression, RA with high myostatin levels (≥17 ng/mL) was found to increase the risk of cachexia ( , 95% CI: 1.24-6.29; ) and LSMM ( , 95% CI: 1.17-7.89; ). Conclusions. High serum myostatin levels increase the risk of LSMM and rheumatoid cachexia. We propose that high myostatin levels are useful biomarkers for the identification of patients in risk of rheumatoid cachexia and myopenia.

Background: Muscle wasting, also known as myopenia, is frequent in rheumatoid arthritis (RA). To date, it is still unknown if the failure of pharmacologic therapies increases the risk of myopenia in RA. Objective: To identify if treatment failure with conventional synthetic DMARDs (csDMARDs) constitutes an independent risk factor of muscle wasting in women with RA. Methods: This was a cross-sectional study. We included 277 women with RA. Assessments in RA patients included: clinical, epidemiological, and therapeutic variables. The skeletal muscle index (SMI) was estimated by DXA, and myopenia was diagnosed if they had an SMI < 5.45 kg/m². Multivariable logistic regression models identified risk factors of myopenia. Results: Muscle wasting was observed in 28.2% of patients with RA. The risk factors of myopenia in RA were menopausal (OR: 4.45, 95% CI: 1.86 to 10.64) and failure of combined therapy with csDMARDs (OR: 2.42, 95% CI: 1.15 to 5.07). The increased body mass index was protective (OR:0.81, 95% CI: 0.75 to 0.87). Conclusions: Around one of four patients with RA presented muscle wasting. Muscle wasting is related to treatment failure of combined csDMARDs; other factors influencing the presence of muscle wasting is being postmenopausal, whereas, the body mass index was a protective factor.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects synovial joints and that frequently involves extra-articular organs. A multiplicity of interleukins (IL) participates in the pathogenesis of RA, including IL-6, IL-1β, transforming growth factor-beta (TGF-β), and tumor necrosis factor (TNF)-α; immune cells such as monocytes, T and B lymphocytes, and macrophages; and auto-antibodies, mainly rheumatoid factor and anti-citrullinated protein antibodies (ACPAs). Skeletal muscle is also involved in RA, with many patients developing muscle wasting and sarcopenia. Several mechanisms are involved in the myopenia observed in RA, and one of them includes the effects of some interleukins and myokines on myocytes. Myostatin is a myokine member of the TGF-β superfamily; the overproduction of myostatin acts as a negative regulator of growth and differentiates the muscle fibers, limiting their number and size. Recent studies have identified abnormalities in the serum myostatin levels of RA patients, and these have been found to be associated with muscle wasting and other manifestations of severe RA. This review analyzes recent information regarding the relationship between myostatin levels and clinical manifestations of RA and the relevance of myostatin as a therapeutic target for future research.

Background and Objectives: According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), sepsis is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection”. The increased presence of free radicals causes an increase in oxidative stress. Vitamin C is an essential water-soluble vitamin with antioxidant activity and immunoregulatory effects that plays a potential role in the treatment of bacterial infections. Our aim was to evaluate the effectiveness of adding vitamin C to the conventional treatment of sepsis to decrease its mortality rate. Materials and Methods: In a prospective cohort study, we included patients with a diagnosis of sepsis and a SOFA score ≥ 9 who were evaluated in an Intensive Care Unit at a secondary-care hospital. According to the intensive care specialist, they were treated using two different strategies: Group 1—patients with sepsis treated with conventional treatment without vitamin C; Group 2—patients with sepsis with the addition of vitamin C to conventional treatment. Results: We included 34 patients with sepsis. The incidence of mortality was 38%, and 47% of patients used vitamin C as an adjuvant to the basic treatment of sepsis. In the basal analyses, patients treated with use of vitamin C compared to patients treated without vitamin C required less use of glucocorticoids (75% vs. 100%, p = 0.039). At follow-up, patients treated without vitamin C had higher mortality than patients treated with vitamin C as an adjuvant for the treatment of sepsis (55.6% vs. 18.8%, p = 0.03). We observed that the use of vitamin C was a protective factor for mortality in patients with sepsis (RR: 0.54, 95% CI: 0.31–0.96, p = 0.03). Conclusions: The use of vitamin C as an adjuvant to treatment decreases the risk of mortality by 46% in patients with sepsis and SOFA ≥ 9 compared to patients treated without vitamin C as an adjuvant to sepsis.

Background: Ankylosing spondylitis (AS) is a chronic autoinflammatory rheumatic disease mainly affecting the sacroiliac joints and spine, causing altered bone remodeling. Pro-inflammatory cytokines such as TNF-α and IL-17 contribute to bone loss by modulating pathways including Wnt/β-catenin, which is inhibited by proteins like Dickkopf-1 (DKK-1) and sclerostin (SOST). Bone morphogenetic protein-6 (BMP-6) promotes osteoblast differentiation and bone formation. This study evaluated the association between serum levels of DKK-1, SOST, BMP-6, and bone mineral density (BMD) in AS patients treated with anti-TNF agents and conventional synthetic DMARDs (csDMARDs). Methods: A cross-sectional study included 76 AS patients diagnosed by modified New York criteria and 30 healthy donors matched by age and sex. BMD at the lumbar spine and hips was assessed by DXA in all participants. Disease activity (BASDAI) and functional index (BASFI) were measured in AS patients. Serum levels of DKK-1, SOST, BMP-6, TNF-α, and IL-17 were quantified by ELISA in both groups. AS patients were divided into two treatment groups: combined anti-TNFα and csDMARD therapy (n = 38), and only csDMARDs (n = 38). Results: Bone mineral density showed no significant statistical differences between the spine (p = 0.930) and hips (p = 0.876) in AS patients compared to healthy controls. The activity (BASDAI) and functionality (BASFI) scores were similar in both treatment groups (p = 0.161 and p = 0.271, respectively). No significant differences were found in serum levels of DKK-1 (p = 0.815), SOST (p = 0.771), BMP-6 (p = 0.451), or IL-17 (p = 0.335) between combined anti-TNFα and csDMARD therapy versus monotherapy with csDMARD. Conclusions: The combination of anti-TNF bDMARD therapy and csDMARD therapy is not significantly associated with serum levels of DKK-1, SOST, BMP-6, and BMD compared to those treated with csDMARD monotherapy in patients with AS. This study provides novel and clinically relevant evidence on how anti-TNF bDMARDs and csDMARDs differentially affect bone turnover biomarkers and bone health in patients with AS, contributing to a better understanding of therapeutic strategies and guiding future research and clinical decision-making.