Autoantibodies against apolipoprotein A1 as potential anti–G protein-coupled receptor class antibodies

Background Functional antibodies targeting GPCRs have gained a role in homeostatic processes whose imbalance may contribute to autoimmune, cardiovascular, and other diseases.Autoantibodies anti-apolipoprotein-A1(AAA-1) are elevated in autoimmune and high cardiovascular-risk condition correlating with adverse outcome. Purpose Because AAA-1 shares in vitro and in vivo characteristics with other anti-GPCR antibodies, we sought to assess its association with anti-GPCRs in acute coronary syndrome (ACS) patients and to evaluate its potential to trigger GPCR activation in vitro. Methods AAA-1, anti-Adrenoreceptor α1, β1, and β2, anti-CXCR3, anti-PAR-1, anti-PAR-4 antibodies were measured by ELISA technique (CellTrend) on serum samples from 221 consecutive ACS patients. Spearman associations were tested using STATISTICA software. AAA-1 screening activation of GPCRs was tested using the in vitro PathHunter®b-Arrestin assay (Eurofins Discovery). Results Significant Spearman associations were found between AAA-1 and anti-GPCR antibodies continuous values. AAA-1 and anti-GPCRs titers are differentially and significantly associated with clinical variables related to cardiovascular and metabolic conditions and outcomes. In vitro screening experiments on 336 GPCRs targets, highlight the capacity of AAA-1 to activate four GPCR members, showing AAA-1 being a direct agonist for PAR-1, PAR-4, and a positive allosteric modulator for Adrenoreceptor-β1, and β2 but not α1. Conclusion These results clearly show the potential AAA-1 as a novel class of anti-GPCRs antibodies. Anti-GPCRs antibodies and AAA-1 emerge as significant players in MI and metabolic conditions. Continued research is warranted to elucidate the underlying mechanisms and to develop targeted therapies that could improve the management and outcomes of patients with MI and metabolic disorders.