TY - JOUR
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.
N1 - Funding Information:
Dr. England’s work was supported by the University of Nebraska Medical Center Physician-Scientist Training Program, 阀nternal Medicine Scientist Development Award, and Mentored Scholars Program. Dr. Poole’s work was supported by the N 阀⬀ (National 阀nstitute of Environmental ?ealth Sciences grant R01-ES-019325). Dr. Mikuls’ work was supported by the US Department of Veterans A 贀airs (merit award CX000896) and the N 阀⬀ (National 阀nstitute of General Medical Sciences grant U54-GM-115458, National 阀nstitute on Alcohol Abuse and Alcoholism grant R25-AA-020818, and National 阀nstitute of Arthritis and Musculoskeletal and Skin Diseases grant 2P50-AR-60772). 1Bryant R. England, MD, Michael J. Duryee, MS, Geo 贀rey M. Thiele, PhD, Ted R. Mikuls, MD, MSP?: VA Nebraska–Western 阀owa ?ealth Care System and University of Nebraska Medical Center, Omaha; 2Punyasha Roul, MS,
Publisher Copyright:
© 2019, American College of Rheumatology
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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U2 - 10.1002/art.40900
DO - 10.1002/art.40900
M3 - Article
C2 - 30933423
AN - SCOPUS:85069736841
SN - 2326-5191
VL - 71
SP - 1483
EP - 1493
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 9
ER -