VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center, Omaha.
University of Nebraska Medical Center, Omaha.
Arthritis Rheumatol. 2019 Sep;71(9):1483-1493. doi: 10.1002/art.40900. Epub 2019 Jul 22.
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.
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.
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.
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.
比较类风湿关节炎相关间质性肺病（RA-ILD）患者血清中丙二醛-乙醛（anti-MAA）抗体水平和肺组织中 MAA 的表达与对照组。
测量 RA-ILD 患者的抗-MAA 抗体（IgA、IgM、IgG）浓度，并与慢性阻塞性肺疾病（COPD）和无肺部疾病的 RA 患者进行比较。使用多变量逻辑回归评估抗-MAA 抗体与 RA-ILD 之间的关联。RA-ILD、其他间质性肺病或肺气肿患者以及对照组（每组 3 例）的肺组织均进行 MAA、瓜氨酸、巨噬细胞（CD68）、T 细胞（CD3）、B 细胞（CD19/CD27）和细胞外基质蛋白（II 型胶原、纤维连接蛋白、波形蛋白）染色。对组织表达和与 MAA 的共定位进行定量和比较。
在 1823 名 RA 患者中，90 名患有 RA-ILD。RA-ILD 患者血清 IgA 和 IgM 抗-MAA 抗体浓度高于 RA 合并 COPD 或 RA 患者（P=0.005）。调整协变量后，IgA 抗-MAA 抗体浓度最高四分位数（比值比 2.09 [95%置信区间 1.11-3.90]）和 IgM（比值比 2.23 [95%置信区间 1.19-4.15]）与 RA-ILD 的存在显著相关。RA-ILD 肺组织中的 MAA 表达高于所有其他组（P<0.001），并且与瓜氨酸（r=0.79）、CD19+B 细胞（r=0.78）和细胞外基质蛋白（II 型胶原[r=0.72]和波形蛋白[r=0.77]）的共定位程度最大。
RA 患者血清 IgA 和 IgM 抗-MAA 抗体与 ILD 相关。MAA 在 RA-ILD 肺组织中高度表达，与其他 RA 自身抗原、自身反应性 B 细胞和细胞外基质蛋白共定位，突出了其在 RA-ILD 发病机制中的潜在作用。
