PRIMARY PULMONARY-HYPERTENSION, TISSUE-PLASMINOGEN ACTIVATOR ANTIBODIES, AND HLA-DQ7

Antibodies to fibrin-bound tissue plasminogen activator (tPA) have bee n found in autoimmune diseases with vascular injury, such as systemic lupus erythematosus and scleroderma. The purpose of this study was to determine whether patients with primary pulmonary hypertension (PPH) h ave an immunogenetically determined response to fibrin-bound tPA. Anti bodies to fibrin-bound tPA were determined in three patient groups: 45 adults with PPH, 41 children with PPH, and 40 children with anatomica lly large congenital pulmonary to systemic communications (PHT+shunt). The frequencies of the HLA class II (DRB1,3,4,5, and -DQB1) alleles i n there three patient groups were compared with those of 51 healthy Ca ucasian control subjects. Fibrin-bound tPA antibodies were found in fo ur of 45 (9%) adults with PPH, four of 41 (10%) children with PPH, and one of 40 (2.5%) children with PHT-shunt. HLA class II typing, which was available for seven of nine Caucasians with fibrin-bound tPA antib odies, revealed that six of seven (86%) patients typed HLA-DQ7 (DQB10 301) and one typed HLA-DQ6. The 86% frequency of HLA-DQ7 in the antibo dy positive patients was significant compared with the 29% frequency i n the healthy control subjects (p = 0.007, p corrected [pc] = 0.05, OR = 14.4). Of interest, these antibody-positive patients, although lack ing antiphospholipid antibodies, shared an amino acid epitope, common to HLA-DQB106,07 and 08 subtypes, which was previously reported to be associated with the lupus anticoagulant. In conclusion, antibodies to fibrin-bound tPA and HLA-DQ7, and possibly the same epitope associate d with the lupus anticoagulant, defined a small subset of children and adults with PPH.