In the last decade, a growing number of GPCRs have been noticed that are targeted by Abs in SSc disease such as functional Abs with agonistic effects on AT1R, ETAR, CXCR3, CXCR4, and protease-activated receptor-1 (PAR-1) as well as Abs with antagonistic effects on Muscarinic-3 Acetylcholine Receptor (M3R), where altered levels of these Abs, their cross-reactivity, and their synergistic effects influence the SSc pathogenesis (Figure 2). Here, CXCR4 is linked to systemic sclerosis.