Soluble interleukin-2 receptor levels in patients with dermatitis herpetiformis

To determine the role of T-cell activation in dermatitis herpetiformis (DH), soluble IL-2R levels were measured by enzyme-linked immunosorbent assay (ELISA) in the sera of 30 patients with DH. Levels of this shed receptor are considered to be a measure of in vivo T-lymphocyte activation, and are elevated in the sera of many patients with inflammatory and immune-mediated diseases. Fifteen of the thirty (50%) patients with DH had elevated levels of soluble IL-2R compared to one of 31 (3%) healthy HLA-B8 or HLA-DR3 control subjects (p less than 0.00001) and one of 10 (10%) healthy non-HLA-B8/-DR3 subjects (p less than 0.0018). In addition, the mean soluble IL-2R level in the patients with DH (744 +/- 381 U/ml) was also significantly higher than that seen in 31 healthy HLA B8 or HLA DR3 individuals (388 +/- 160 U/ml, p = 0.0001) and 10 healthy non-HLA-B8/DR3 individuals (397 +/- 201 U/ml, p = 0.002). Only two of the 30 patients with DH had active skin lesions at the time of serum sampling, one of whom had elevated levels of IL-2R. Measurement of soluble IL-2R levels in sequential serum samples, available in four patients with DH at times of active and inactive skin disease, demonstrated a temporal association between soluble IL-2R level elevations and active skin disease in two patients and no association in two patients. In one patient a marked elevation in soluble IL-2R levels occurred with the onset of gastrointestinal symptoms, which decreased by 14% with institution of a gluten-free diet. In order to determine if soluble IL-2R levels are related to the mucosal immune response, the IL-2R levels were compared to the level of IgA antibodies directed against the dietary antigen beta-lactoglobulin. Ten of eleven (91%) patients with circulating IgA anti-beta lactoglobulin antibodies were also found to have elevated levels of IL-2R. In contrast, in the patients with no detectable IgA anti-beta lactoglobulin antibodies, only four of 16 (25%) had elevated levels of IL-2R (p = 0.001). Because IL-2R levels are not related to activity of the skin disease in patients with DH but are associated with the presence of IgA antibodies against the dietary antigen beta-lactoglobulin, these results suggest that some of the T-cell activation commonly present in DH reflects an ongoing immune response in the gastrointestinal tract.