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 pulmonary hypertension in human immunodeficiency virus (HIV) infection is unclear. The objective of this study was to determine whether patients 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 two control groups: 128 HIV-negative Caucasians and a previously reported group of 97 HIV-positive, racially mixed control subjects. In those with PPH, there was a significantly increased frequency of HLA-DR6 (-DRB1*1301/2 subtypes) and of HLA-DR52 (DRB3*0301 subtype). These findings suggest that HIV-associated PPH reflects a host response to HIV-1 determined by one or more HLA-DR alleles located within the major histocompatibility complex. The same HLA-DR6 subtype found at increased frequency in our patients has previously been associated with the development of a CD8 lymphocytic host response to HIV-1, termed diffuse infiltrative lymphocytosis syndrome (DILS), which resembles autoimmune Sjogren's disease and is associated with prolonged survival. Together, these findings suggest that HIV-positive PPH may represent a clinical outcome that has similarities with that resulting from the immunogenetically determined host response present in DILS.
Morse
J H
JH
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Barst
R J
RJ
Itescu
S
S
Flaster
E R
ER
Sinha
G
G
Zhang
Y
Y
Fotino
M
M
D000328:Adult; D000483:Alleles; D002648:Child; D004198:Disease Susceptibility; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications* / Q000235:genetics / Q000276:immunology*; D008297:Male; D011379:Prognosis
D000949:Histocompatibility Antigens Class II