Malondialdehyde–Acetaldehyde Adducts and Antibody Responses in Rheumatoid Arthritis–Associated Interstitial Lung Disease

Bryant England, Michael J. Duryee, Punyasha Roul, Tina D. Mahajan, Namrata Singh, Jill A Poole, Dana P. Ascherman, Liron Caplan, M. Kristen Demoruelle, Kevin D. Deane, Lynell Warren Klassen, Geoffrey Milton Thiele, Ted R Mikuls

Research output: Contribution to journalArticle

Abstract

Objective: To compare serum anti–malondialdehyde–acetaldehyde (anti-MAA) antibody levels and MAA expression in lung tissue from patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD) to those found in controls. Methods: Anti-MAA antibody (IgA, IgM, IgG) concentrations were measured in patients with RA-ILD and compared to those of RA patients with chronic obstructive pulmonary disease (COPD) and RA patients without lung disease. Associations between anti-MAA antibody with RA-ILD were assessed using multivariable logistic regression. Lung tissue from patients with RA-ILD, other ILD, or emphysema, and from controls (n = 3 per group) were stained for MAA, citrulline, macrophages (CD68), T cells (CD3), B cells (CD19/CD27), and extracellular matrix proteins (type II collagen, fibronectin, vimentin). Tissue expression and colocalization with MAA were quantified and compared. Results: Among 1,823 RA patients, 90 had prevalent RA-ILD. Serum IgA and IgM anti-MAA antibody concentrations were higher in RA-ILD than in RA with COPD or RA alone (P = 0.005). After adjustment for covariates, the highest quartiles of IgA anti-MAA antibody concentration (odds ratio 2.09 [95% confidence interval 1.11–3.90]) and IgM (odds ratio 2.23 [95% confidence interval 1.19–4.15]) were significantly associated with the presence of RA-ILD. MAA expression in RA-ILD lung tissue was greater than in tissue from all other groups (P < 0.001), and it colocalized with citrulline (r = 0.79), CD19+ B cells (r = 0.78), and extracellular matrix proteins (type II collagen [r = 0.72] and vimentin [r = 0.77]) to the greatest degree in RA-ILD. Conclusion: Serum IgA and IgM anti-MAA antibody is associated with ILD among RA patients. MAA is highly expressed in RA-ILD lung tissue, where it colocalizes with other RA autoantigens, autoreactive B cells, and extracellular matrix proteins, highlighting its potential role in the pathogenesis of RA-ILD.

Original languageEnglish (US)
Pages (from-to)1483-1493
Number of pages11
JournalArthritis and Rheumatology
Volume71
Issue number9
DOIs
StatePublished - Sep 1 2019

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Interstitial Lung Diseases
Antibody Formation
Immunoglobulin A
Immunoglobulin M
Extracellular Matrix Proteins
Antibodies
Lung
Citrulline
B-Lymphocytes
Collagen Type II
Vimentin
Chronic Obstructive Pulmonary Disease
Serum
Odds Ratio
Confidence Intervals
Emphysema
Autoantigens
Fibronectins
Lung Diseases
Anti-Idiotypic Antibodies

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Malondialdehyde–Acetaldehyde Adducts and Antibody Responses in Rheumatoid Arthritis–Associated Interstitial Lung Disease. / England, Bryant; Duryee, Michael J.; Roul, Punyasha; Mahajan, Tina D.; Singh, Namrata; Poole, Jill A; Ascherman, Dana P.; Caplan, Liron; Demoruelle, M. Kristen; Deane, Kevin D.; Klassen, Lynell Warren; Thiele, Geoffrey Milton; Mikuls, Ted R.

In: Arthritis and Rheumatology, Vol. 71, No. 9, 01.09.2019, p. 1483-1493.

Research output: Contribution to journalArticle

England, Bryant ; Duryee, Michael J. ; Roul, Punyasha ; Mahajan, Tina D. ; Singh, Namrata ; Poole, Jill A ; Ascherman, Dana P. ; Caplan, Liron ; Demoruelle, M. Kristen ; Deane, Kevin D. ; Klassen, Lynell Warren ; Thiele, Geoffrey Milton ; Mikuls, Ted R. / Malondialdehyde–Acetaldehyde Adducts and Antibody Responses in Rheumatoid Arthritis–Associated Interstitial Lung Disease. In: Arthritis and Rheumatology. 2019 ; Vol. 71, No. 9. pp. 1483-1493.
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abstract = "Objective: To compare serum anti–malondialdehyde–acetaldehyde (anti-MAA) antibody levels and MAA expression in lung tissue from patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD) to those found in controls. Methods: Anti-MAA antibody (IgA, IgM, IgG) concentrations were measured in patients with RA-ILD and compared to those of RA patients with chronic obstructive pulmonary disease (COPD) and RA patients without lung disease. Associations between anti-MAA antibody with RA-ILD were assessed using multivariable logistic regression. Lung tissue from patients with RA-ILD, other ILD, or emphysema, and from controls (n = 3 per group) were stained for MAA, citrulline, macrophages (CD68), T cells (CD3), B cells (CD19/CD27), and extracellular matrix proteins (type II collagen, fibronectin, vimentin). Tissue expression and colocalization with MAA were quantified and compared. Results: Among 1,823 RA patients, 90 had prevalent RA-ILD. Serum IgA and IgM anti-MAA antibody concentrations were higher in RA-ILD than in RA with COPD or RA alone (P = 0.005). After adjustment for covariates, the highest quartiles of IgA anti-MAA antibody concentration (odds ratio 2.09 [95{\%} confidence interval 1.11–3.90]) and IgM (odds ratio 2.23 [95{\%} confidence interval 1.19–4.15]) were significantly associated with the presence of RA-ILD. MAA expression in RA-ILD lung tissue was greater than in tissue from all other groups (P < 0.001), and it colocalized with citrulline (r = 0.79), CD19+ B cells (r = 0.78), and extracellular matrix proteins (type II collagen [r = 0.72] and vimentin [r = 0.77]) to the greatest degree in RA-ILD. Conclusion: Serum IgA and IgM anti-MAA antibody is associated with ILD among RA patients. MAA is highly expressed in RA-ILD lung tissue, where it colocalizes with other RA autoantigens, autoreactive B cells, and extracellular matrix proteins, highlighting its potential role in the pathogenesis of RA-ILD.",
author = "Bryant England and Duryee, {Michael J.} and Punyasha Roul and Mahajan, {Tina D.} and Namrata Singh and Poole, {Jill A} and Ascherman, {Dana P.} and Liron Caplan and Demoruelle, {M. Kristen} and Deane, {Kevin D.} and Klassen, {Lynell Warren} and Thiele, {Geoffrey Milton} and Mikuls, {Ted R}",
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T1 - Malondialdehyde–Acetaldehyde Adducts and Antibody Responses in Rheumatoid Arthritis–Associated Interstitial Lung Disease

AU - England, Bryant

AU - Duryee, Michael J.

AU - Roul, Punyasha

AU - Mahajan, Tina D.

AU - Singh, Namrata

AU - Poole, Jill A

AU - Ascherman, Dana P.

AU - Caplan, Liron

AU - Demoruelle, M. Kristen

AU - Deane, Kevin D.

AU - Klassen, Lynell Warren

AU - Thiele, Geoffrey Milton

AU - Mikuls, Ted R

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N2 - Objective: To compare serum anti–malondialdehyde–acetaldehyde (anti-MAA) antibody levels and MAA expression in lung tissue from patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD) to those found in controls. Methods: Anti-MAA antibody (IgA, IgM, IgG) concentrations were measured in patients with RA-ILD and compared to those of RA patients with chronic obstructive pulmonary disease (COPD) and RA patients without lung disease. Associations between anti-MAA antibody with RA-ILD were assessed using multivariable logistic regression. Lung tissue from patients with RA-ILD, other ILD, or emphysema, and from controls (n = 3 per group) were stained for MAA, citrulline, macrophages (CD68), T cells (CD3), B cells (CD19/CD27), and extracellular matrix proteins (type II collagen, fibronectin, vimentin). Tissue expression and colocalization with MAA were quantified and compared. Results: Among 1,823 RA patients, 90 had prevalent RA-ILD. Serum IgA and IgM anti-MAA antibody concentrations were higher in RA-ILD than in RA with COPD or RA alone (P = 0.005). After adjustment for covariates, the highest quartiles of IgA anti-MAA antibody concentration (odds ratio 2.09 [95% confidence interval 1.11–3.90]) and IgM (odds ratio 2.23 [95% confidence interval 1.19–4.15]) were significantly associated with the presence of RA-ILD. MAA expression in RA-ILD lung tissue was greater than in tissue from all other groups (P < 0.001), and it colocalized with citrulline (r = 0.79), CD19+ B cells (r = 0.78), and extracellular matrix proteins (type II collagen [r = 0.72] and vimentin [r = 0.77]) to the greatest degree in RA-ILD. Conclusion: Serum IgA and IgM anti-MAA antibody is associated with ILD among RA patients. MAA is highly expressed in RA-ILD lung tissue, where it colocalizes with other RA autoantigens, autoreactive B cells, and extracellular matrix proteins, highlighting its potential role in the pathogenesis of RA-ILD.

AB - Objective: To compare serum anti–malondialdehyde–acetaldehyde (anti-MAA) antibody levels and MAA expression in lung tissue from patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD) to those found in controls. Methods: Anti-MAA antibody (IgA, IgM, IgG) concentrations were measured in patients with RA-ILD and compared to those of RA patients with chronic obstructive pulmonary disease (COPD) and RA patients without lung disease. Associations between anti-MAA antibody with RA-ILD were assessed using multivariable logistic regression. Lung tissue from patients with RA-ILD, other ILD, or emphysema, and from controls (n = 3 per group) were stained for MAA, citrulline, macrophages (CD68), T cells (CD3), B cells (CD19/CD27), and extracellular matrix proteins (type II collagen, fibronectin, vimentin). Tissue expression and colocalization with MAA were quantified and compared. Results: Among 1,823 RA patients, 90 had prevalent RA-ILD. Serum IgA and IgM anti-MAA antibody concentrations were higher in RA-ILD than in RA with COPD or RA alone (P = 0.005). After adjustment for covariates, the highest quartiles of IgA anti-MAA antibody concentration (odds ratio 2.09 [95% confidence interval 1.11–3.90]) and IgM (odds ratio 2.23 [95% confidence interval 1.19–4.15]) were significantly associated with the presence of RA-ILD. MAA expression in RA-ILD lung tissue was greater than in tissue from all other groups (P < 0.001), and it colocalized with citrulline (r = 0.79), CD19+ B cells (r = 0.78), and extracellular matrix proteins (type II collagen [r = 0.72] and vimentin [r = 0.77]) to the greatest degree in RA-ILD. Conclusion: Serum IgA and IgM anti-MAA antibody is associated with ILD among RA patients. MAA is highly expressed in RA-ILD lung tissue, where it colocalizes with other RA autoantigens, autoreactive B cells, and extracellular matrix proteins, highlighting its potential role in the pathogenesis of RA-ILD.

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