Additionally, CD40/CD154 and ICOS/ICOS-L interaction, altered peptide ligands (APLs), and p38 mitogen-activated protein kinase (p38MAPK) signaling are believed to play differential roles in activating adaptive immune responses (26, 61, 62) or blister formation in the pathogenesis of pemphigus (63), potentially providing new targets for the treatment of pemphigus. This evidence concerns the gene ICOS and pemphigus.