Moreover, hypotheses related to the link between autoantibodies and microvascular damage in SSc derive also from the insights inherent to functional antibodies described in SSc patients whose most relevant identified targets appear to be endothelin 1 type A receptor (ETAR), angiotensin II type 1 receptor (AT1R), muscarinic receptor 3 (M3R), PDGFR, chemokine receptors CXCR3 and CXCR4, estrogen receptor α and cluster of differentiation 22 (CD22) [52]. This evidence concerns the gene ESR1 and systemic sclerosis.