Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with increased risk of cardiovascular disease and metabolic alterations. The mechanisms underlying these alterations remain unclear. Ghrelin is a gastrointestinal hormone with potent effects on food intake, body weight, metabolism, and immune response. Recent studies reported the presence of anti-ghrelin autoantibodies in healthy subjects and the levels and affinity of these autoantibodies were altered in anorectic and obese individuals. In this cross-sectional study we analyzed anti-ghrelin autoantibodies in RA patients and evaluated its relationship with clinical, body-composition and metabolic parameters. Clinical measurements of RA patients included the disease activity score-28 (DAS-28), inflammatory biomarkers, autoantibodies (RF and anti-CCP), body composition, glucose and lipid profile. Serum ghrelin levels were measured by enzyme-linked immunosorbent assay (ELISA). Free and total anti-ghrelin autoantibodies quantification (IgG and IgA isotypes) was performed by in-house ELISA. RA patients had lower IgG anti-ghrelin autoantibodies levels and higher immune complexes percentage (IgG+ghrelin) compared to the control group, while the IgA anti-ghrelin autoantibodies showed no significant differences. In the bivariate analysis, the percentage of IgG anti-ghrelin immune complexes positively correlated with BMI and ghrelin whereas in the multivariate regression model, the variables associated were DAS-28, body weight, visceral fat, LDL-C and TG (
R
2
= 0.72). The percentage of IgA anti-ghrelin immune complexes positively correlated with RF and anti-CCP and the multivariate regression model showed an association with RF and body fat percentage (
R
2
= 0.22). Our study shows an increased percentage of IgG anti-ghrelin immune complexes in RA patients despite ghrelin levels were similar in both groups, suggesting an increase in the affinity of these autoantibodies toward ghrelin. The associations found in the multiple regression analysis for anti-ghrelin immune complexes support the previously reported functions of these natural autoantibodies as carriers and modulators of the stability and physiological effect of the hormone. However, in RA both the disease activity and the RF appear to influence the formation of these anti-ghrelin immune complexes.
Studies have demonstrated the presence of low-affinity immunoglobulins (Igs) directed to leptin, a key hormone of the neuroendocrine axis that regulates appetite and metabolism, in adult healthy subjects, patients with obesity and type 2 diabetes mellitus. In the present exploratory study, IgG leptin-reactive antibodies were analyzed for the first time in children and adolescents according to body mass index (BMI) and were correlated with biochemical profile (lipid profile, insulin, glucose and leptin) and metabolic risk indexes (HOMA-IR, HOMA-β, AIP). One hundred and thirty-six participants were included (children n=63, adolescents n=73). An in-house ELISA test was performed to measure IgG anti-leptin antibodies (free, total and immune complexes). In adolescents, free and total IgG anti-leptin antibodies levels were higher in groups with overweight or obesity than in normal-weight group (p<0.01), while in children, the total fractions were lower in groups with overweight and obesity than in normal-weight (p<0.02). Immune complexes percentage showed opposite correlations with BMI in children (r=0.4004, p=0.0473) and adolescents (r=-0.3983, p=0.0133). IgG anti-leptin antibodies were also correlated with HOMA-IR in children (r=-0.4569, p=0.0217) and adolescents (r=-0.3589, p=0.0316), and with AIP (r=-0.3608, p=0.0261) in adolescents. Our data suggest that the production and affinity of IgG anti-leptin antibodies can be affected by age, body composition and metabolic conditions; additionally, in normal conditions, IgG anti-leptin antibodies may have a protective role in insulin resistance and cardiovascular events.
Estudio del impacto del índice de masa corporal pretrasplante sobre el pronto funcionamiento del injerto renal Studying the impact of body mass index on pretransplant early renal graft function
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