Antibodies against Small Ubiquitin-like Modifier Activating Enzyme May Be a Protective Factor from Rapid Progressive Interstitial Lung Disease in Patients Bearing Antibodies against Melanoma Differentiation Associated Gene 5

Hung-Cheng Tsai; Wei-Sheng Chen; Yi-Syuan Sun; Chien-Chih Lai; Ying-Ying Yang; Wen-Ru Chou; Hsien-Tzung Liao; Chang-Youh Tsai; Chung-Tei Chou

doi:10.3390/jcm13030725

Antibodies against Small Ubiquitin-like Modifier Activating Enzyme May Be a Protective Factor from Rapid Progressive Interstitial Lung Disease in Patients Bearing Antibodies against Melanoma Differentiation Associated Gene 5

J Clin Med. 2024 Jan 26;13(3):725. doi: 10.3390/jcm13030725.

Authors

Hung-Cheng Tsai^{1

2}, Wei-Sheng Chen^{1

2}, Yi-Syuan Sun^{1

2

3}, Chien-Chih Lai^{1

2}, Ying-Ying Yang^{2

3

4

5}, Wen-Ru Chou^{6

7}, Hsien-Tzung Liao^{1

2}, Chang-Youh Tsai^{7

8}, Chung-Tei Chou¹

Affiliations

¹ Division of Allergy, Immunology & Rheumatology, Taipei Veterans General Hospital, Taipei 112, Taiwan.
² Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan.
³ Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei Campus, Taipei 112, Taiwan.
⁴ Division of Clinical Skills Training Center, Department of Medical Education, Taipei Veterans General Hospital, Taipei 112, Taiwan.
⁵ Department of Medical Education, Taipei Veterans General Hospital, Taipei 112, Taiwan.
⁶ Division of Chest Medicine, Department of Medicine, Fu Jen Catholic University Hospital, 69 Guitz Rd., New Taipei City 24352, Taiwan.
⁷ School of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan.
⁸ Division of Immunology & Rheumatology, Department of Medicine, Fu Jen Catholic University Hospital, 69 Guitz Rd., New Taipei City 24352, Taiwan.

Abstract

Background: Anti-MDA5 antibody-bearing (anti-MDA5⁺)-dermatomyositis (DM) or polymyositis (PM) is notorious for causing rapidly progressive interstitial lung disease (RPILD) and/or cancers with high mortality rate. However, anti-MDA5 antibodies (Abs) are also found in other connective tissue diseases and their link with RPILD, especially with regard to the mortality rate, are unknown. Methods: We retrospectively recruited 71 patients bearing anti-MDA5-Abs in serum, stratified them in terms of a presence or absence of RPILD, and evaluated their clinical features, laboratory findings, associated myositis antibodies, concurrent connective tissue disease (CTD) as well as newly developed malignancies. Results: In total, 39 (55%) patients presented with DM/PM, but 32 (45%) did not. In total, 22 of the former and 11 of the latter developed RPILD eventually, accounting for a total of 46% of all MDA-5 bearing patients. On the other hand, 15 of all 71 (21.1%) patients had cancers. Among the 32 patients who did not have DM/PM, 27 (38.0% of all 71) had other CTDs, indicating that only 5 (7.0% of 71) patients did not have CTDs. Senility (odds ratio (OR) = 1.816, p = 0.032), presence of anti-Ro-52 antibody (OR = 1.676, p = 0.018), elevated C-reactive protein (CRP, OR = 4.354, p < 0.001) and carcinoembryonic antigen (CEA, OR = 2.625, p = 0.005) posed risks for RPILD. High lactose dehydrogenase (LDH, p = 0.009), CRP (p = 0.001) and CEA (p = 0.001), ferritin (p ≤ 0.001) and low albumin (p ≤ 0.001) were significantly associated with mortality. Anti-SAE antibodies were negatively correlated with RPILD as analyzed by univariate (OR = 0.245, p = 0.017) and multivariate (OR = 0.058, p = 0.036) regressions, indicating that they may be a protective factor in relation to RPILD (OR = 0.543, p = 0.008) or fatality (OR = 0.707, p = 0.012), which was also demonstrated in subgroup analyses. Conclusions: In contrast to various risk factors for RPILD or mortality, anti-SAE antibodies might conversely be a protective factor in anti-MDA5⁺ patients.

Keywords: anti-MDA5 antibodies; anti-SAE antibodies; dermatomyositis (DM); rapidly progressive interstitial lung disease (RPILD).

Abstract

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