Elevated levels of soluble humanleukocyte antigen-G in the airways are a marker for a low-inflammatory endotype of asthma

White, Steven R.; Nicodemus‐Johnson, Jessie; Laxman, Bharathi; Denner, Darcy R.; Naureckas, Edward T.; Hogarth, D. Kyle; Stern, Randi; Minc, Alexa; Solway, Julian; Sperling, Anne I.; Ober, Carole

doi:10.1016/j.jaci.2017.02.031

Cited by 13 publications

(19 citation statements)

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“…These results reinforce the involvement of HLA-G in asthma and suggest that the modulation of local sHLA-G associated with asthma phenotypes and asthma inflammation markers described in Ref. ( 9 ) might be partly driven by HLA-G genetic polymorphism.…”

Section: Discussionsupporting

confidence: 82%

“…This study would benefit from the replication of pertinent results in additional cohorts to support the pertinence of defining HLA-G haplotype as a predictive genetic marker for asthma. Whereas the mechanisms with which HLA-G expression modulates asthma severity or phenotype are still poorly understood, it appears clearer that bronchial HLA-G expression is a more reliable marker than systemic and peripheral expression [( 9 ) and our data]. However, given the discomfort of taking BAL samples and cross-reactivity in HLA-G antibody capture assays, HLA-G haplotype sequencing offers a reproducible qualitative marker that can be obtained from a sampling method which is easy to implement.…”

Section: Discussionmentioning

confidence: 99%

“…In asthma, soluble HLA-G (sHLA-G) expression was reported to be higher in bronchoalveolar lavage (BAL) from asthmatic individuals and in both plasma and serum from atopic asthmatic children, whereas others reported no difference in non-allergic asthmatics ( 5 – 8 ). In BAL from asthmatic patients, however, sHLA-G expression was reported to be inversely correlated with markers of asthma inflammation ( 9 ). Our group reported an impairment of full-length protein HLA-G expression in HBEC from asthmatic patients and abnormal expression of alternatively spliced membrane-bound (HLA-G1 to 4) and soluble (HLA-G5 to 7) forms ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

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HLA-G Haplotypes Are Differentially Associated with Asthmatic Features

et al. 2018

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Human leukocyte antigen (HLA)-G, a HLA class Ib molecule, interacts with receptors on lymphocytes such as T cells, B cells, and natural killer cells to influence immune responses. Unlike classical HLA molecules, HLA-G expression is not found on all somatic cells, but restricted to tissue sites, including human bronchial epithelium cells (HBEC). Individual variation in HLA-G expression is linked to its genetic polymorphism and has been associated with many pathological situations such as asthma, which is characterized by epithelium abnormalities and inflammatory cell activation. Studies reported both higher and equivalent soluble HLA-G (sHLA-G) expression in different cohorts of asthmatic patients. In particular, we recently described impaired local expression of HLA-G and abnormal profiles for alternatively spliced isoforms in HBEC from asthmatic patients. sHLA-G dosage is challenging because of its many levels of polymorphism (dimerization, association with β2-microglobulin, and alternative splicing), thus many clinical studies focused on HLA-G single-nucleotide polymorphisms as predictive biomarkers, but few analyzed HLA-G haplotypes. Here, we aimed to characterize HLA-G haplotypes and describe their association with asthmatic clinical features and sHLA-G peripheral expression and to describe variations in transcription factor (TF) binding sites and alternative splicing sites. HLA-G haplotypes were differentially distributed in 330 healthy and 580 asthmatic individuals. Furthermore, HLA-G haplotypes were associated with asthmatic clinical features showed. However, we did not confirm an association between sHLA-G and genetic, biological, or clinical parameters. HLA-G haplotypes were phylogenetically split into distinct groups, with each group displaying particular variations in TF binding or RNA splicing sites that could reflect differential HLA-G qualitative or quantitative expression, with tissue-dependent specificities. Our results, based on a multicenter cohort, thus support the pertinence of HLA-G haplotypes as predictive genetic markers for asthma.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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HLA-G Haplotypes Are Differentially Associated with Asthmatic Features

et al. 2018

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“…PGE2, a negative regulator of type 2 innate lymphoid cell response 63 , is a mediator of cough variant asthma 64,65 in whom half studied are nonatopic and nearly two-thirds women 66,67 . Soluble HLA-G is both a biomarker of the T2-low asthma endotype 68 and a tolerance inducing MHC molecule that facilitates implantation at the fetal-maternal interface 69 . It is found in T2-low severe asthma in whom two-thirds studied were women and fifty percent on oral glucocorticosteroids 68 .…”

Section: Discussionmentioning

confidence: 99%

Asthma and/or hay fever as predictors of fertility/impaired fecundity in U.S. women: National Survey of Family Growth

Turkeltaub¹,

Lockey

Holmes

et al. 2019

Sci Rep

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This study addresses whether asthma and/or hay fever predict fertility and impaired fecundity. The lifetime number of pregnancies (fertility) and spontaneous pregnancy losses (impaired fecundity) in 10,847 women representative of the U.S. population 15 to 44 years of age with histories of diagnosed asthma and/or hay fever are analyzed in the 1995 National Survey of Family Growth using multivariable Poisson regression with multiple covariates and adjustments for complex sampling. Smokers have significantly increased fertility compared to nonsmokers. Smokers with asthma only have significantly increased fertility compared to other smokers. Higher fertility is associated with impaired fecundity (ectopic pregnancy, miscarriage, stillbirth). Women with asthma (with and without hay fever) have significantly higher pregnancy losses than women without asthma. With increasing number of pregnancies, smokers have increased pregnancy losses compared to nonsmokers. Smokers, especially those with asthma only, have increased fertility and require special attention as to their family planning needs, reproductive health, and smoking cessation. Women with asthma, regardless of number of pregnancies, and smokers with higher numbers of pregnancies have high risk pregnancies that require optimal asthma/medical management prenatally and throughout pregnancy. Whether a proinflammatory asthma endotype underlies both the increased fertility and impaired fecundity associated with age and smoking is discussed.

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“…A description of the clinical protocol and methods is provided in the Methods section in this article's Online Repository at www.jacionline.org, and data from a subset of these subjects have previously been reported. 8,9 A total of 68 control subjects with no history of pulmonary disease and 124 subjects with asthma defined by the Expert Panel Report 3 guidelines on asthma were studied. The clinical characteristics of the subjects are shown in Table I.…”

Section: To the Editormentioning

confidence: 99%

Evidence for an IL-6–high asthma phenotype in asthmatic patients of African ancestry

White

Laxman

Naureckas

et al. 2019

Journal of Allergy and Clinical Immunology

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Elevated levels of soluble humanleukocyte antigen-G in the airways are a marker for a low-inflammatory endotype of asthma

Abstract: Summary Soluble human leukocyte antigen-G (sHLA-G), an immunomodulatory molecule associated with suppression of inflammation, is elevated in the airways of asthmatic patients with a low inflammatory endotype as evidenced by low airway eosinophils and low exhaled nitric oxide.

Cited by 13 publications

References 10 publications

HLA-G Haplotypes Are Differentially Associated with Asthmatic Features

HLA-G Haplotypes Are Differentially Associated with Asthmatic Features

Asthma and/or hay fever as predictors of fertility/impaired fecundity in U.S. women: National Survey of Family Growth

Evidence for an IL-6–high asthma phenotype in asthmatic patients of African ancestry

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