PRIMARY PULMONARY-HYPERTENSION - IMMUNOGENETIC RESPONSE TO HIGH-MOBILITY GROUP (HMG) PROTEINS AND HISTONE

HLA class II alleles (DNA typing) and antibodies to HMG-1,2, 14, 17 pr oteins and H1 histone were determined in three predominantly Caucasian groups of patients with pulmonary hypertension (PHT). Forty-four adul ts had primary pulmonary hypertension (PPH), 42 children had PPH, and 41 children had PHT associated with anatomically large congenital pulm onary to systemic shunts (PHT + shunt). The HLA class II alleles in th e Caucasian patients were compared with those of 51 healthy Caucasian controls. Eight (18%) of 44 sera from adults with PPH bound HMG-14 and 23 (52%) bound H1. None of 42 sera from children with PPH bound eithe r HMG-14/17 or HMG-1/2, whereas four (10%) bound H1. In the PHT + shun t group of 41 children, two (5%) bound HMG-14, one (3%) bound HMG-17, four (10%) bound HMG-1 and/or HMG-2, and six (15%) bound H1. Among the 12 HMG antibody-positive patients, HLA-DQ6 was present in nine of 10 HLA typed patients (six PPH adults and three PHT + shunt children), se ven of whom had antibodies to HMG-14 and one to HMG-17. The 100% frequ ency of HLA-DQ6 in seven Caucasian patients with antibodies to HMG-14/ 17 was statistically significant when compared with the 41% frequency of -DQ6 present in 51 healthy Caucasian controls (pc=0.027, pc=Bonferr oni correction, OR = 21.3). In contrast, when compared with controls, 25 patients with PPH and anti-HI antibodies (21 adults and four childr en) had increased frequencies of HLA-DQ7 and -DR5 (60% versus 29%, P = 0.010, OR = 3.6 and 48% versus 22%, P = 0.018, OR = 3.4), which were not significant after correction. In essence, antibodies to HMG-14 and to HI proteins were present predominantly in adults with PPH, suggest ing that the pattern of response to HMG-14/17 was similar to that prev iously reported in systemic lupus erythematosus (SLE) and drug-induced autoimmunity. This is the first report of an association between auto antibodies directed against HMG and H1 with immunogenetic markers. The se data suggest that a subset of patients with PPH may have an autoimm une disease.