Association of High-Altitude Pulmonary Edema With the Major Histocompatibility Complex

Abstract

Background-A constitutional susceptibility has been suggested in the development of high-altitude pulmonary edema (HAPE) because HAPE generally affects healthy young people, some of whom suffer recurrent episodes. We examined whether immunogenetic susceptibility is present in HAPE-susceptible subjects. Methods and Results-The frequencies of human leukocyte antigen (HLA) alleles in 28 male and 2 female subjects with a history of HAPE were compared with those in 100 healthy volunteers. We assayed the HLA-A, -B, -C, -DR, and -DQ antigens serologically. The pulmonary hemodynamics on admission to the hospital and the ventilatory response to hypoxia and hypercapnia were retrospectively examined in 10 of the HAPE-susceptible subjects. HLA-DR6 was positive in 14 (46.7%) of the subjects with HAPE but only 16.0% of the control subjects (Pϭ.0005), and HLA-DQ4 was positive in 12 (40.0%) of the subjects with HAPE but only 10.0% of the control subjects (Pϭ.0001). HLA-DR6 or HLA-DQ4 was positive in 8 (100%) of the subjects with recurrent HAPE. The pulmonary arterial pressure on admission of the HLA-DR6 -positive subjects with HAPE was significantly higher than that of the HLA-DR6 -negative subjects with HAPE. Conclusions-There were significant associations of HAPE with HLA-DR6 and HLA-DQ4 and of pulmonary hypertension with HLA-DR6. An immunogenetic susceptibility, which is associated with HLA class II alleles located within the major histocompatibility complex, may underlie the development of HAPE, at least in some of its forms.

Ventilatory chemoresponsiveness, narcolepsy-cataplexy and human leukocyte antigen DQB1*0602 status

“…Few studies hint at potential relationships between immune markers and hypoxia. Microsatellite markers within the HLA region are reported to correlate with a blunted response to hypoxia in COPD with type II respiratory failure [24] and with the development of altitude-induced pulmonary oedema [25], although correlations specific for the DQB1*0602 allele were not reported in these studies. Intercross studies of C3H/HeJ (C3) and C57BL/6J (B6) mice have mapped potential loci for the hypoxic effect and its modulation by hypercapnia [26]; however, these regions are not syntenic to human HLA gene regions.…”

Positive Association of the Endothelial Nitric Oxide Synthase Gene Polymorphisms With High-Altitude Pulmonary Edema

“…PAP, pulmonary artery wedge pressure (PAWP), and cardiac output (CO) were measured by the method described previously. 19 PVR was calculated by subtracting PAWP from mean PAP and dividing by CO. PVR index and cardiac index were also calculated.…”

Physical activity at moderate and high altitudes. Cardiovascular and respiratory morbidit

“…It is accompanied by pulmonary hypertension, an increase in the pulmonary capillary permeability and hypoxemia 48 . HAPE typically occurs in young and healthy mountaineers and is precipitated by rapid ascents at altitudes above 2,500-3,000m 45,[48][49][50] . There is an individual susceptibility and it tends to recur 45,48,49,51 .…”

“…HAPE typically occurs in young and healthy mountaineers and is precipitated by rapid ascents at altitudes above 2,500-3,000m 45,[48][49][50] . There is an individual susceptibility and it tends to recur 45,48,49,51 . HAPE clinically manifests 2 to 5 days after acute exposure to hypobaric hypoxia, 78% of the cases appear until the 10 th day 38,45 , with the following symptoms: abnormal dyspnea on effort and, later, even at rest, cyanosis, dry cough that evolves to a mucous-sanguinolent cough, and tachycardia 19,38 .…”

“…Hanaoka et al 49 showed that some human lymphocyte antigens (HLA) are increased in Japanese patients with HAPE, especially those with the recurrent disease. HLA-DR6 and/or HLA-DR4 were most frequently found in Japanese individuals with HAPE than in a control group.…”