Nonbullous pemphigoid (NBP) is a pemphigoid variant, in which for unknown reason patients do not develop blisters. In bullous pemphigoid (BP) accumulating evidence suggests a role for IgE in disease pathogenesis, and possibly in blister formation. This study assessed the presence of IgE in serum and skin of BP and NBP, using enzyme linked immunosorbent assay (ELISA) and immunofluorescence techniques. We included 67 NBP and 50 BP serum samples, and control sera of 25 pemphigus patients, and 25 elderly patients with pruritus. Total IgE was elevated in 60% and 63% of BP and NBP, and in 20% and 60% of pemphigus and elderly controls. IgE ELISAs were more frequently positive in BP than in NBP (NC16A 18% vs. 9%, p=0.139; BP230 34% vs. 22%, p=0.149). Surprisingly, elderly controls had IgE antibodies to NC16A and BP230 in 8% and 20%, while all pemphigus controls were negative. Increased total IgE correlated with positive anti-NC16A IgE ELISA in BP (p=0.007), and positive anti-BP230 IgE ELISA in NBP (p=0.000), while such association was not found in elderly controls (NC16A p=1.000, BP230 p=0.061). Skin biopsies of 14 BP and 14 NBP patients with highest anti-NC16A IgE ELISA titers were stained for IgE for direct immunofluorescence microscopy. Two biopsies (7%; 1 NBP, 1 BP) showed linear IgE along the basement membrane zone, while IgE was mostly bound to the surface of dermal cells (71% NBP, 86% BP). In conclusion, IgE was present in serum and skin of both NBP and BP patients, suggesting a supportive role of IgE  instead of being a key mediator of blister formation in pemphigoid.

IgE in skin and serum of nonbullous and bullous pemphigoid patients