Author(s): MOOREN, J., MOOREN, F., TESCHLER, M., HEIDECKE, H., BLOCH, W., JAVELLE, F., WAHL, P. , Institution: GERMAN SPORT UNIVERSITY COLOGNE, Country: GERMANY, Abstract-ID: 1640

INTRODUCTION:
G Protein-coupled receptors (GPCRs) are the largest superfamily of integral membrane proteins and are key contributors to physiological responses to stress, exertion, and immunity. While autoantibodies (AABs) against GPCRs are well described in pathological conditions, especially increasing with age, they are also detectable in healthy individuals and athletes without autoimmune diseases. However, their regulatory function in endurance-trained (ET) populations remains unclear. Therefore, this study investigated whether ET status, age, and their interaction are associated with differences in circulating GPCR-AAB levels, with particular emphasis on sex-related patterns.
METHODS:
Serum samples from 59 healthy, non-smoking participants (28 female) were collected alongside anthropometric data and cardiopulmonary exercise testing using a ramp protocol on a cycle ergometer. Participants were assigned to four groups based on ET status and age: trained young (TY), trained old (TO), untrained young (UY), and untrained old (UO). Trained (T) did at least 7 hours of ET per week, while untrained (U) did up to 2 hours. Young participants were between 18-30 years and old between 55-70 years. GPCR-AAB levels (AABs against Angiotensin II receptor 1, Endothelin-1 receptor type A, Alpha- and Beta-Adrenergic receptors 1/2, Muscarinic Acetylcholine receptor M3, and CXC Motif Chemokine receptor 3) were quantified using enzyme-linked immunosorbent assay (ELISA). Data were analyzed by Mann-Whitney-U-, Kruskal-Wallis, and Spearman tests. Total AAB counts were analyzed after z-transformation.
RESULTS:
Across all AABs, a trend towards higher levels in T compared to U groups appeared (p=0.067). A sex-dependent effect was found with higher AAB levels in males (p=0.0003), while no age-dependent effect was observed (p=0.147). In more detail, TY displayed higher levels than UY (p=0.016), and UO likewise exceeded UY (p=0.037). Notably, higher levels in men and reduced inter-individual variance in women were particularly observed within the ET group, as well as across both age groups (p≤0.024). Analyzing individual AABs, a significant higher level of CXCR3-AABs was found in men (p=0.05). Additionally, inside the trained group, 6 out of 7 AABs targeting receptors involved in autonomic cardiovascular regulation were higher in males compared to females (p≤0.039).
CONCLUSION:
These findings indicate distinct training- and sex-related patterns in GPCR-AABs, with consistently higher levels in ET men. This raises the question of whether ET is associated with reduced autoreactivity in females. Additionally, CXCR3-AABs showed a significant difference between sexes, potentially reflecting anti-inflammatory effects due to female hormonal status. These findings indicate that GPCR-AABs should be interpreted within a multifactorial framework integrating sex, age, training status, and physiological condition rather than as isolated biomarkers. This study should be expanded to larger cohorts and in-depth immunological analysis.