Evidence map›Paper›PMID 40846486›Full record

ArticleThorax2025

Serum IgA isotypes are associated with percent emphysema, wall thickness and lung function decline.

Tess Pottinger, Zhonghua Liu, Lili Liu, Kristina L Buschur, Jeffrey L Curtis, Ani Manichaikul, Stephen S Rich, Victor E Ortega, Eugene R Bleecker, Deborah A Meyers and 5 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Thorax, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

15 authors.

Tess PottingerDepartment of Medicine, Columbia University Irving Medical Center, New York, New York, USA tdp2117@cumc.columbia.edu.ORCID 0000-0003-0647-5712
Zhonghua LiuDepartment of Biostatistics, Columbia University Irving Medical Center, New York, New York, USA.
Lili LiuDepartment of Medicine, Division of Nephrology, Columbia University Irving Medical Center, New York, New York, USA.
Kristina L BuschurDepartment of Medicine, Columbia University Irving Medical Center, New York, New York, USA.
Jeffrey L CurtisDivision of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Ani ManichaikulCenter for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
Victor E OrtegaDepartment of Internal Medicine, Division of Respiratory Diseases, Center for Individualized Medicine, Mayo Clinic, Scottsdale, Arizona, USA.
Eugene R BleeckerDepartment of Medicine, University of Arizona, Tucson, Arizona, USA.
Deborah A MeyersDepartment of Medicine, University of Arizona, Tucson, Arizona, USA.
Eric A HoffmanDepartment of Radiology, University of Iowa, Iowa City, Iowa, USA.
Benjamin SmithDepartment of Medicine, Columbia University Irving Medical Center, New York, New York, USA.
Jan NovakDepartment of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Krzysztof KirylukDepartment of Medicine, Division of Nephrology, Columbia University Irving Medical Center, New York, New York, USA.
R Graham BarrDepartment of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Pulmonary Toxicology Facility CoreP30ES005605 · NIEHS · UNIVERSITY OF IOWA · PI Jong Sung Kim · 1990 to 2026
$40.5M
Wake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3M
SPIROMICS II: Biological underpinnings of COPD heterogeneity and progressionU01HL137880 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WOODRUFF, PRESCOTT G · 2017 to 2021
$27.9M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
Pulmonary microvascular perfusion in the Multi-Ethnic Study of AtherosclerosisR01HL077612 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI R Graham BARR · 2004 to 2026
$18.8M
Task Area A Core Study Operations.Task Area A shall encompass annual follow-up of cohort members, clinical endpoints ascertainment, study coordination activities, maintenance of the database and biosp75N92020D00001 · NHLBI · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, ROBYN LEAGH · 2020 to 2025
$17.2M
Understanding the Origins of Early COPDR01HL144718 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI CURTIS, JEFFREY LOUIS, HAN, MEILAN K · 2020 to 2024
$11.3M
Studies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5M
Rare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9M
Elucidating IgA Nephropathy through Genetic Studies of IgA1 GlycosylationR01DK082753 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GHARAVI, ALI G, NOVAK, JAN · 2009 to 2024
$8.7M
NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NHGRI NIH HHS U54 HG003067NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS HHSN268200900013CNHLBI NIH HHS HHSN268200900014CNHLBI NIH HHS HHSN268200900015CNHLBI NIH HHS HHSN268200900016CNHLBI NIH HHS HHSN268200900017CNHLBI NIH HHS HHSN268200900018CNHLBI NIH HHS HHSN268200900019CNHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS L30 HL170347NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS R01 HL077612NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL144718NHLBI NIH HHS T32 HL144442NHLBI NIH HHS U01 HL120393NHLBI NIH HHS U01 HL137880NHLBI NIH HHS U24 HL141762NIDDK NIH HHS K01 DK137031NIDDK NIH HHS R01 DK078244NIDDK NIH HHS R01 DK082753NIDDK NIH HHS R01 DK105124NIDDK NIH HHS R56 DK078244NIEHS NIH HHS P30 ES005605
6 · The paper itself

Abstract

rationaleImmunoglobulin A (IgA) deficiency, a rare, highly heritable trait, is associated with frequent pulmonary infections, emphysema, airway changes and low lung function; however, it is unclear if reduced IgA levels may affect lung structure and function.

methodsSerum IgA, IgA1 and galactose-deficient IgA1 (Gd-IgA1) levels were measured in the population-based Multi-Ethnic Study on Atherosclerosis (MESA). The MESA Lung Study measured percent emphysema on cardiac CT and airway dimensions on chest CT, and performed spirometry. Regression models were evaluated after adjustment for demographic and CT factors. Mendelian randomisation (MR) analyses were conducted using genetic variants from the Trans-Omics for Precision Medicine (TOPMed) programme. A replication analysis was performed in the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS). MEASUREMENTS AND MAIN

resultsAmong 5497 participants, lower log-normalised serum IgA levels were associated with greater percent emphysema (β=-0.084; 95% CI -0.14 to -0.026; p=0.005), which was confirmed on MR (β=-0.79; 95% CI -1.4 to -0.18; p=0.011). Greater log-normalised serum Gd-IgA1 levels were associated with airway wall thickness (β=0.0079; 95% CI 0.0017 to 0.014; p=0.012; n=2580) and decline in the forced expiratory volume in one second (FEV1) (β=-0.012; 95% CI -0.021 to -0.0036; p=0.0055; n=2778) and FEV1/forced vital capacity (FVC) ratio (β=-0.0028; 95% CI -0.0048 to -0.00084; p=0.0054; n=2778).

conclusionLower serum IgA levels were associated with greater percent emphysema. Additionally, higher Gd-IgA1 levels were associated with airway wall thickness and lung function decline. These findings support a protective role of IgA in emphysema pathogenesis and possible deleterious role of Gd-IgA1 in airway diseases.

Indexed as

Immunoglobulin ALungPulmonary EmphysemaAgedFemaleForced Expiratory VolumeHumansMaleMendelian Randomization AnalysisMiddle AgedSpirometryTomography, X-Ray ComputedVital CapacityImmunoglobulin AEmphysemaForced Expiratory VolumeImaging/CT MRI etc

Identifiers

PMID40846486
PMCPMC12530317

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.