title: Primary pulmonary hypertension: immunogenetic response to high-mobility group (HMG) proteins and histone.
abstract: HLA class II alleles (DNA typing) and antibodies to HMG-1,2,14,17 proteins and H1 histone were determined in three predominantly Caucasian groups of patients with pulmonary hypertension (PHT). Forty-four adults had primary pulmonary hypertension (PPH), 42 children had PPH, and 41 children had PHT associated with anatomically large congenital pulmonary to systemic shunts (PHT + shunt). The HLA class II alleles in the 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 either HMG-14/17 or HMG-1/2, whereas four (10%) bound H1. In the PHT + shunt 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), seven of whom had antibodies to HMG-14 and one to HMG-17. The 100% frequency 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 = Bonferroni correction, OR = 21.3). In contrast, when compared with controls, 25 patients with PPH and anti-H1 antibodies (21 adults and four children) 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 H1 proteins were present predominantly in adults with PPH, suggesting that the pattern of response to HMG-14/17 was similar to that previously reported in systemic lupus erythematosus (SLE) and drug-induced autoimmunity. This is the first report of an association between autoantibodies directed against HMG and H1 with immunogenetic markers. These data suggest that a subset of patients with PPH may have an autoimmune disease.
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Morse
authors.forename: R J
authors.initials: RJ
authors.lastname: Barst
authors.forename: M
authors.initials: M
authors.lastname: Fotino
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: E
authors.initials: E
authors.lastname: Flaster
authors.forename: M J
authors.initials: MJ
authors.lastname: Fritzler
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001323:Autoantibodies / Q000032:analysis*; D015551:Autoimmunity; D004247:DNA / Q000032:analysis; D006609:High Mobility Group Proteins / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006657:Histones / Q000276:immunology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000276:immunology*; D007125:Immunogenetics
chemical_list: D001323:Autoantibodies; D006609:High Mobility Group Proteins; D000949:Histocompatibility Antigens Class II; D006657:Histones; D004247:DNA