Immunologic Disturbances in Primary Pulmonary Hypertension

Morse, Jane H.; Barst, Robyn J.

doi:10.1055/s-2007-1006366

Cited by 7 publications

(7 citation statements)

References 40 publications

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“…The release of inflammatory cytokines and vasoconstricting mediators could follow any of these pathways. 23 We 24 recently reported that endothelin-1 is a vasoconstrictor that contributed to the pulmonary hypertension in HAPE. We also showed that there were significant increases in the levels of total cells (especially macrophages and neutrophils), total protein, albumin, IL-1, IL-6, IL-8, and tumor necrosis factor-␣ in bronchoalveolar lavage fluid in patients with HAPE compared with the values after recovery, suggesting that an inflammatory process may occur in HAPE.…”

Section: Discussionmentioning

confidence: 95%

“…Multiple heterogeneous immunologic events also play a role in the development of pulmonary hypertension. 23 The possible routes include vasculitis with immune complex deposition, the induction of activation molecules such as HLA class II on endothelial cells with inflammatory infiltrates, and release of cytokines and mediators (T-cell-mediated vascular injury) and initiation of noninflammatory vasculopathy via procoagulant activity (recurrent thromboembolism, thrombosis in situ, or both). The release of inflammatory cytokines and vasoconstricting mediators could follow any of these pathways.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 1998

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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.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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

et al. 1998

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“…MORSE and BARST [29] speculated that the induction of activation molecules, such as HLA class II, on endothelial cells with inflammatory infiltrates, and the release of cytokines and mediators, as well as the initiation of noninflammatory vasculopathy via recurrent thromboembolism or thrombosis in situ, or both, might be related to the pathogenesis of pulmonary arterial hypertension. A previous study by the authors showed that the circulating levels of monocyte chemoattractant protein-1, tumour necrosis factor alpha (TNF-a), and interleukin-1b were high in CTEPH [20].…”

Section: Discussionmentioning

confidence: 99%

Association of clinical features with HLA in chronic pulmonary thromboembolism

Tanabe

Kimura²,

Amano³

et al. 2005

Eur Respir J

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The aetiology of chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown and may be heterogeneous, because there are several ethnic differences in the clinical characteristics of CTEPH. Female predominance and a higher ratio of chronic to acute pulmonary thromboembolism have been reported in Japan as compared with the USA. Because such ethnic differences may be controlled by genetic factors, the current study investigated HLA polymorphisms in Japanese patients with CTEPH.HLA typing by serological and/or DNA typing methods was performed (for HLA-A, B, DPB1, DRB1) in 80 patients and 678 controls, and the association of clinical characteristics with HLA alleles was studied.The frequencies of HLA-B*5201 (40 versus 24%) and DPB1*0202 (19 versus 6%) were significantly higher in the patients. HLA-B*5201 positive patients showed a significant female predominance. Total pulmonary vascular resistance and mixed venous oxygen tension were better in the HLA-B*5201 positive patients. In contrast, cardiac index and gas exchange parameters were worse in the HLA-DPB1*0202 positive patients. In the patients carrying HLA-B*5201 and/or -DPB1*0202, the frequency of deep vein thrombosis was significantly lower than the other patients.These observations suggested that both the susceptibility and clinical characteristics of chronic thromboembolic pulmonary hypertension were controlled in part by the HLA-B and -DPB1 loci.

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“…Primary pulmonary hypertension (PPH) is a well described clinical entity of unknown etiology [1]. The increased frequencies of Raynaud's phenonon [1], antinuclear antibodies [2], and the anti-Ku autoantibody [3] found in patients with PPH have prompted the hypothesis that PPH could be an autoimmune disease [4][5][6][7]. Pulmonary hypertension (PHT), often resembling PPH, can also be a clinical component of connective tissue diseases (CTD) including systemic lupus erythematosus (SLE) [8,9], scleroderma [10], rheumatoid arthritis (RA) [11], dermatomyositis [12] and mixed connective tissue disease [13].…”

Section: Introductionmentioning

confidence: 99%

Primary pulmonary hypertension: immunogenetic response to high-mobility group (HMG) proteins and histone

Morse

Barst

Fotino

et al. 1996

Clinical and Experimental Immunology

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SUMMARYHLA 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.

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Immunologic Disturbances in Primary Pulmonary Hypertension

Cited by 7 publications

References 40 publications

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

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

Association of clinical features with HLA in chronic pulmonary thromboembolism

Primary pulmonary hypertension: immunogenetic response to high-mobility group (HMG) proteins and histone

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