Metabolic syndrome in rheumatoid arthritis patients: Relationship among its clinical components.

BACKGROUND: Metabolic syndrome (MetS) prevalence in rheumatoid arthritis (RA) patients is known to vary considerably across the world. This study aimed to determine the prevalence of MetS in RA patients from western Mexico and to analyze the interrelation of the MetS components with the clinical variables of RA. METHODS: This case-control study included 216 RA patients and 260 control subjects (CS). MetS prevalence was determined according to the NCEP/ATP III and the Latin American Consensus of the Latin American Diabetes Association (ALAD) criteria. RESULTS: MetS was observed in 30.6% RA patients and 33.3% of controls (p > 0.05) according to NCEP/ATP III and 28.7% in RA patients and 31.1% for controls using ALAD criteria. Total cholesterol, LDL-C, and Castelli's I-II indexes were lower in RA (p < 0.001) than in CS. The RA patients with MetS had more swollen joints than those without MetS (p = 0.018). In RA patients with MetS, DAS-28 score correlated with smoking index (rho = 0.4601, p = 0.0004) and VLDL-C (rho = 0.3108, p = 0.0056); similarly, rheumatoid factor (RF) correlated with age (rho = 0.2031, p = 0.0027), smoking index (rho = 0.3404, p < 0.0001), triglycerides (rho = 0.1958, p = 0.0039), and VLDL-C (rho = 0.1761, p = 0.0162). CONCLUSIONS: The MetS prevalence in RA patients from western Mexico is not higher than controls; however, in RA patients with MetS, some inflammatory markers are associated with MetS components; thus, the control of MetS in RA could be beneficial to regulate disease activity.

Transforming growth factor beta isoforms and TGF-ßR1 and TGF-ßR2 expression in systemic sclerosis patients.

Systemic sclerosis (SSc) is characterized by chronic inflammation and fibrosis, two processes associated with transforming growth factor ß (TGF-ß) functions. In the present study, we investigated the expression of TGF-ß isoforms in serum and the skin distribution of TGF-ß and two receptors (TGF-ßR1 and TGF-ßR2) and their relationship with some clinical, inflammatory, autoimmune (autoantibodies), and vascular (platelets) biomarkers in SSc patients. A total of 56 SSc patients and 120 control subjects (CS) were included. The serum levels of TGF-ß isoforms were quantified by immunoassay with magnetic microspheres, and the skin biopsies were processed by immunohistochemistry. The soluble levels of the three active TGF-ß isoforms were lower in SSc patients than in CS (p < 0.0001). However, sTGF-ß1 and sTGF-ß3 levels were positively correlated with C-reactive protein levels in SSc patients. Additionally, sTGF-ß2 and sTGF-ß3 levels were positively correlated with the number of platelets in SSc patients. In skin biopsies, TGF-ß1, TGF-ßR1, and TGF-ßR2 expression levels were higher in SSc patients than CS. In conclusion, this is the first study showing a joint decrease of the 3 active TGF-ß isoforms in SSc patients. However, TGF-ß1, TGF-ßR1, and TGF-ßR2 are possibly increased in clinically involved skin. Therefore, it is likely that a distinct role is played by TGF-ß at the local (skin lesions) and systemic levels in SSc patients.

TGFB1 mRNA expression and frequency of the + 869T>C and + 915G>C genetic variants: impact on risk for systemic sclerosis.

Systemic Sclerosis (SSc) is a chronic autoimmune disease characterized by immune disorder, microvascular damage, and fibrosis. TGFB1 gene encodes for the transforming growth factor isoform 1 (TGF-ß1), one of the most important pro-fibrotic cytokines. Therefore, variants in TGFB1 and changes in its expression could be associated with the pathogenesis of SSc. We aimed to evaluate the association of TGFB1 variants (+ 869T>C [rs1982073] and + 915G > C [rs1800471]) with the TGFB1 mRNA expression and SSc risk in the Southern Mexican population. We included 56 SSc patients and 112 control subjects (CS). The genetic variants were determined by the PCR-RFLP method. The TGFB1 mRNA expression was determined by qPCR. For the + 869T>C variant, the C allele was associated with SSc risk (OR = 1.733; CI = 1.087-2.762; p = 0.020). The C allele for the + 915G>C variant was also associated with SSc risk (OR = 11.168; CI = 1.289-96.754; p = 0.023). The relative expression of TGFB1 mRNA was 1.77-fold lower in SSc patients than in CS. Carriers of polymorphic alleles (TC or CC genotypes) for the + 869T>C variant showed 3.7-fold lower mRNA expression than the TT genotype in patients and 4.81-fold lower in CS. For the + 915G>C variant, patients with GA genotype had 1.78-fold lower mRNA expression than GG genotype carriers. In conclusion, the present study showed that + 869T>C and + 915G>C variants could be SSc risk factors for patients from Southern Mexico, and these genetic variants could induce lower mRNA expression of TGFB1.

Neutralizing Antibodies against SARS-CoV-2, Anti-Ad5 Antibodies, and Reactogenicity in Response to Ad5-nCoV (CanSino Biologics) Vaccine in Individuals with and without Prior SARS-CoV-2.

This is the first study outside of clinical trials (phase I-III) evaluating the ability of the Ad5-nCoV vaccine to generate neutralizing antibodies and the factors associated with optimal or suboptimal response. In a longitudinal assay, 346 people (117 with prior COVID-19 and 229 without prior COVID-19) vaccinated with Ad5-nCoV were recruited. The percentage of neutralizing antibodies against SARS-CoV-2 (Surrogate Virus Neutralization Test) and antibodies against Ad5 (ADV-Ad5 IgG ELISA) were quantified pre and post-vaccination effects. The Ad5-nCoV vaccine induces higher neutralizing antibodies percentage in individuals with prior COVID-19 than those without prior COVID-19 (median [IQR]: 98% [97-98.1] vs. 72% [54-90], respectively; p < 0.0001). Furthermore, a natural infection (before vaccination) induces more neutralizing antibodies percentage than immunized individuals without prior COVID-19 (p < 0.01). No patient had vaccine-severe adverse effects. The age, antidepressant, and immunosuppressive treatments, reactogenicity, and history of COVID-19 are associated with impaired antibody production. The anti-Ad5 antibodies increased after 21 days of post-vaccination in all groups (p < 0.01). We recommend the application of a booster dose of Ad5-nCoV, especially for those individuals without previous COVID-19 infection. Finally, the induction of anti-Ad5 antibodies after vaccination should be considered if a booster with the same vaccine is planned.

TNFA -308G>A and -238G>A polymorphisms and risk to systemic sclerosis: impact on TNF-α serum levels, TNFA mRNA expression, and autoantibodies.

Systemic sclerosis (SSc) is a rare autoimmune disease with high mortality, characterized by chronic inflammation and fibrosis, which are processes associated with higher serum tumor necrosis factor-α (sTNF-α) levels. TNFA -308G>A and -238G>A polymorphisms have been associated with higher sTNF-α levels. In this study, we genotyped the TNFA -308G>A and -238G>A polymorphisms in 53 SSc patients and 115 unrelated control subjects (CS) from southern Mexico. The TNFA mRNA expression and sTNF-α levels were also quantified by qPCR and enzyme-linked immunosorbent assays, respectively. TNFA -308GA genotype was associated with disease susceptibility according to a codominant genetic model (OR = 3.2, 95% CI 1.05-9.75, p = 0.03), and with higher anti-fibrillarin antibodies (p = 0.01), and higher skin thickening (p = 0.006). TNFA -238GA was not associated with SSc risk. TNFA mRNA expression and sTNF-α levels were similar between SSc patients and CS and were not statistically associated with the TNFA polymorphisms; however, a correlation (rho = 0.362, p = 0.009) between sTNF-α levels with anti-RNA polymerase III antibodies was observed in the SSc patients. In conclusion, the -308G>A polymorphism is a genetic marker of SSc susceptibility in population from southern Mexico, and it is associated with skin thickening and anti-fibrillarin antibodies. In addition, sTNF-α levels correlate positively with the anti-RNA pol III antibodies levels.