The newly described distinct associations of HLA class I and II genes with ulcerative colitis (UC) and Crohn's disease (CD) provide strong evidence for genetic heterogeneity of susceptibility between these two major forms of inflammatory bowel disease (IBD), moreover, the familial distribution of anti-neutrophil cytoplasmic antibodies (ANCAs, a subclinical markers) in patient's families has further implicated the existence of heterogeneity within this disease. To test the hypothesis that heterogeneity indicated by ANCAs has a genetic basis that resides within HLA region, we studied 42 IBD Iraqi cases (30 UC and 12 CD) and an ethnically matched healthy control group (n=35). Microlymphocytotoxicity test was used for classes I and II HLA-typing. ANCAs were detected using an ELISA test. It was observed that controls were all p.ANCA-negatives, while 25 (83.3%) and 4 (33.3%) of UC and CD, respectively, were positives for this test. Only 7 (8.57%) of controls were c.ANCA positives, while 7 (23.3%) and 2 (16.6%) of UC and CD patients were positives, respectively. P.ANACApositive IBD patient's status was reported to be positively associated with the frequencies of A11, DR2, DQ1, and DQ2 revealing etiology at the respective EFs : 0.151, 0.185, 0.241, and 0.215. In contrast, B12, Cw4, and DR1 were conferred preventive roles (p.ANCA negatives) at significantly decreased frequencies of IOR; 16.2, 7.3, and10.6, respectively, in addition to DR4 and DQ3 which appeared to have similar roles. On the other hand, A11, A(28+34), and Cw6 were observed in positive associations with c.ANCA-positive patients at respective EFs: 0.342, 0.229, and 0.326. Whoever, no allele was detected to prevent the positivity of this test. Thus, genetic HLA-based heterogeneity has been concluded within ANCA positive\ANCA-negative IBD patients.
