IgG Anti-ghrelin Immune Complexes Are Increased in Rheumatoid Arthritis Patients Under Biologic Therapy and Are Related to Clinical and Metabolic Markers

Abstract

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.

Signaling pathways in rheumatoid arthritis: implications for targeted therapy

“…102 THE PATHOGENESIS OF RA RA is initially a state of continuous cellular activation that results in autoimmunity in joints or other organs. 103,104 The clinical manifestations of the disease occur predominantly following synovial inflammation and joint injury. Fibroblast-like synoviocytes (FLS) play a crucial role in these pathological courses.…”

Sustainable-psycho-nutritional intervention programme for a sustainable diet (the ‘NutriSOS’ study) and its effects on eating behaviour, diet quality, nutritional status, physical activity, metabolic biomarkers, gut microbiota and water and carbon footprints in Mexican population: study protocol of an mHealth randomised controlled trial

“…No. 1001313) (72) . The reference points for glucose values and lipid profiles will be taken from the regulations in force in Mexico (73,74) .…”

“…The reference points for glucose values and lipid profiles will be taken from the regulations in force in Mexico (73,74) . Blood samples will be taken by a nurse from the antecubital vein of each participant, following the protocol from the Mexican Health Secretary (72,75) . After an overnight fast of 8 to 12 hours, samples will be taken by specialists and will be centrifuged at 3500 rpm for 15 min to separate the serum.…”

Ghrelin-Reactive Autoantibodies as Potential Modulators of Dysfunctional Eating Patterns in Women: An Exploratory Study

“…Samples were aliquoted in 0.6 mL microtubes and stored at − 20 °C until the day of assay. To measure IgG ghrelin-reactive autoAbs, a previously validated in-house enzyme-linked immunosorbent assay (ELISA) test adapted by Porchas-Quijada et al [32], and based on the protocol published by Fetissov [33], was performed. This test allows quantification of free (autoAbs unbound to the hormone) and total (autoAbs forming immune complexes with the hormone plus the free form) using two sample dilution buffers to create normal (pH 7.4) or dissociative conditions (pH 8.9).…”