T-helper 2 involvement in the pathogenesis of bullous pemphigoid: role of soluble CD30 (sCD30)

Abstract Bullous pemphigoid (BP) is an autoimmune blistering skin disease in which autoantibodies are directed against hemidesmosomal proteins of basal keratinocytes. The presence of activated T helper cells in lesions and peripheral blood of BP patients, the eosinophilia, the high levels of serum IgE, eosinophil cationic protein and soluble immune products such as IL-2, sIL-2R, IL-5, soluble CD23 (sCD23) strongly suggest the involvement of a cell-mediated immune reaction in which Th2 lymphocytes could play a pivotal role. To seek evidence to support this hypothesis we evaluated serum levels of IL-4 and sCD30, a specific activation marker of cells able to produce Th2-like cytokines, in 25 patients affected with BP. Serum from both healthy donors and pemphigus vulgaris (PV) patients were used as controls. Our results demonstrated significantly higher levels of IL-4 and sCD30 in patients with BP in relation to both normal individuals (16.6 ± 7.9 vs 4.5 ± 2.2 pg/ml, P < 0.0001; 30.3 ± 10 vs 10.5 ± 4 U/ml, P < 0.0001) and PV patients (6.2 ± 4 pg/ml, P < 0.0001; 16 ± 8.5 U/ml, P < 0.0001). Furthermore, a positive correlation between IL-4 and sCD30 was found (R = 0.85, P < 0.0001). In a subset of seven patients observed after systemic immunosuppressive therapy, we detected a significant reduction in sCD30 serum levels (36.9 ± 7.3 vs 16.3 ± 6.8 U/ml, P = 0.002), with a parallel improvement in their clinical condition. These results seem to be consistent with the systemic involvement of Th2 lymphocytes in the pathogenesis of BP and suggest a role for sCD30 as a serological marker of disease activity.