PRIMARY PULMONARY-HYPERTENSION IN HIV-INFECTION - AN OUTCOME DETERMINED BY PARTICULAR HLA CLASS-II ALLELES

Primary pulmonary hypertension (PPH) may have an autoimmune basis that is influenced by host immunogenetics. The pathogenesis of primary pul monary hypertension in human immunodeficiency virus (HIV) infection is unclear. The objective of this study was to determine whether patient s with PPH and HIV infection have distinctive immunogenetic profiles. Ten racially mixed HIV-infected patients with PPH were typed for human leukocyte antigen (HLA) class II (DRB1, 3, 4, 5 and DQB1) by DNA-PCR sequence-specific oligonucleotide probes. Results were compared with t wo control groups: 128 HIV-negative Caucasians and a previously report ed group of 97 HIV-positive, racially mixed control subjects. In those with PPH, there was a significantly increased frequency of HLA-DR6 (- DRB11301/2 subtypes) and of HLA-DR52 (DRB3*0301 subtype). These findi ngs suggest that HIV-associated PPH reflects a host response to HIV-1 determined by one or more HLA-DR alleles located within the major hist ocompatibility complex. The same HLA-DR6 subtype found at increased fr equency in our patients has previously been associated with the develo pment of a CD8 lymphocytic host response to HIV-1, termed diffuse infi ltrative lymphocytosis syndrome (DILS), which resembles autoimmune Sjo gren's disease and is associated with prolonged survival. Together, th ese findings suggest that HIV-positive PPH may represent a clinical ou tcome that has similarities with that resulting from the immunogenetic ally determined host response present in DILS.