Clinical manifestations in 100 Japanese bullous pemphigoid cases in relation to autoantigen profiles

The relationship between clinical findings and antigen profiles in 100 bullous pemphigoid (BP) patients has been investigated. The patients were divided into four groups based upon the results of immunoblot analysis, namely patients whose sera detected the 230-kDa BP antigen (BP230) and the 180-kDa BP antigen (BP180), those recognizing either BP230 or BP180 alone, and those recognizing neither antigen. Analysis by the chi-squared test showed predominant occurrence of oral (P < 0.05) and facial lesions (P < 0.005) in patients whose sera detected BP180, and these patients also tended to have more extensive lesions (P < 0.005). Patients that were positive for BP180 alone needed treatment with higher doses of steroids than the patients positive for BP230 alone (P < 0.05). Furthermore, all five recalcitrant cases, which did not respond well to steroid treatment, were shown to possess autoantibodies against BP180 in their sera. Patients with antibodies to BP230 had a tendency to have a high titre of anti-BMZ antibodies (P < 0.005). These results suggest that anti-BP180 antibodies may be more related to the disease severity than anti-BP230 antibodies. Bullous pemphigoid (BP) is an autoimmune blistering disorder characterized clinically by tense blister formation and immunologically by the presence of tissue-bound and circulating antibasement membrane zone (BMZ) autoantibodies. A number of immunoblot analyses have indicated that two major antigenic proteins of epidermal extracts, the 230-kDa BP antigen (BP230 or BPAG1) and the 180-kDa BP antigen (BP180, BPAG2 or type XVII collagen), are detected by sera from patients with BP in various patterns. Some BP sera recognize both antigen proteins, while others detect only BP230 or BP180 or none. Recently, cDNAs for these antigens have been isolated, and the characteristics for these molecules have been investigated in more detail. The exact relationship between these two proteins is still unclear; however, more recent studies showed that BP180 has an extracellular domain and polyclonal rabbit antibodies raised against an extracellular non-collagenous domain of the murine BP180 antigen were pathogenic in a passive transfer model. Several investigators have suggested a relationship between clinical findings and laboratory data in BP. Arbesman et al. compared the extent and duration of the disease with age, serum levels of IgE, IgA and IgG and titre of anti-BMZ antibodies. The results indicated that serum level of IgE and IgA correlated significantly to the extent of the disease and that titre of anti-BMZ antibodies correlated significantly (only in males) to the duration. There has been only one report which has analysed the relationship between pemphigoid antigens and clinical findings or laboratory data; no correlation was found. In a previous study, the reactivities of BP sera by immunoblotting using human epidermal extracts and two recombinant polypeptides produced from a mouse cDNA clone BPM1 were examined. The results of immunoblotting using epidermal extracts revealed that the two major BP antigens, BP230 and BP180, were detected by 74% and 51% of BP sera, respectively. Comparison of the clinical data with BP antigens gave the impression that the cases whose sera reacted only with BP180 were clinically more severe and less respondent to steroid treatment than the cases which detected BP230 alone on immunoblots. In the study reported here we have examined further the relationship between clinical and immunoblot data by applying a statistical analysis to the results previously obtained.