As HLA-Class II expression in placentas from index cases of CHI within our cohort showed a positive relationship with the extent of C4d deposition and maternal CD68+ macrophage infiltration, it is tempting to speculate that binding of anti-HLA antibodies to the trophoblast may occur in severe cases of CHI, particularly as HLA-Class II expression was observed in proximity to areas of intervillous macrophage infiltration. Here, CD68 is linked to congenital isolated hyperinsulinism.