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

Bryant R. 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 W. Klassen, Geoffrey M. Thiele, Ted R. Mikuls

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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.

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 R.; 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 W.; Thiele, Geoffrey M.; Mikuls, Ted R.

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

Research output: Contribution to journalArticle

England, Bryant R. ; 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 W. ; Thiele, Geoffrey M. ; 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 = "England, {Bryant R.} 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 W.} and Thiele, {Geoffrey M.} 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 R.

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 W.

AU - Thiele, Geoffrey M.

AU - Mikuls, Ted R.

PY - 2019/9/1

Y1 - 2019/9/1

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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