HLA ANTIGENS AND PANCA DEFINE ULCERATIVE-COLITIS AS A GENETICALLY HETEROGENEOUS DISORDER

Background. Several genetic and subclinical markers have been associat ed with ulcerative colitis. Aim. To determine whether a significant as sociation with HLA class I and II antigens was present in Italian ulce rative colitis patients considered as a whole population or stratified according to their anti-neutrophil cytoplasmatic antibodies. Methods. HLA class I and II antigens, were studied by serological typing techn iques and related to the presence of anti-neutrophil cytoplasmatic ant ibodies detected by means of indirect immunofluorescence. Results. Pat ients with ulcerative colitis (n=45) had a significantly increased fre quency of DQ6 (p=0.04) and DQ7 (p=0.003) and a decreased frequency of DQ5 (p=0.03) and DQ8 (p=0.02) when compared with ethnically matched he althy controls (n=252 for HLA class I and 173 for HLA class II). No si gnificant difference in HLA I-and DR-antigens was observed. Anti-neutr ophil cytoplasmatic antibodies were found in 27/45 (60%) ulcerative co litis patients and in 0/252 controls (p<0.001). After stratifying ulce rative colitis patients according to their anti-neutrophil cytoplasmat ic antibodies status, anti-neutrophil cytoplasmatic antibodies + ve pa tients had an increased frequency of A19 (p=0.007), DR2 (p=0.03), and DR15 (p=0.006), and a decreased frequency of Al (p=0.004) compared wit h anti-neutrophil cytoplasmatic antibodies - ve ones. Conclusions. We suggest that specific HLA-class II loci play an important role in the susceptibility to ulcerative colitis in Italy. A subset of ulcerative colitis patients is characterised by the presence of a specific subcli nical marker (anti-neutrophil cytoplasmatic antibodies), which seems t o be genetically determined as shown by the increased frequencies of H LA-A19 and DR2 observed in anti-neutrophil cytoplasmatic antibodies ve ulcerative colitis.