Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 19 December 2023 / Approved: 19 December 2023 / Online: 20 December 2023 (09:53:05 CET)

A peer-reviewed article of this Preprint also exists.

Tsai, H.-C.; Chen, W.-S.; Sun, Y.-S.; Lai, C.-C.; Yang, Y.-Y.; Chou, W.-R.; Liao, H.-T.; Tsai, C.-Y.; Chou, C.-T. 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, 13, 725. Tsai, H.-C.; Chen, W.-S.; Sun, Y.-S.; Lai, C.-C.; Yang, Y.-Y.; Chou, W.-R.; Liao, H.-T.; Tsai, C.-Y.; Chou, C.-T. 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, 13, 725.

Abstract

: Anti-MDA5 antibody bearing (anti-MDA5+)-dermatomyositis (DM) or polymyositis (PM) is notorious for causing rapidly progressive interstitial lung disease (RPILD) &/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 regards to the mortality rate are unknown. 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. Thirty-nine (55%) patients presented with DM/PM but 32 (45%) didn’t. Twenty-two of the former and 11 of the latter developed RPILD eventually, accounting for a total of 46% of all MDA5 bearing patients. On the other hand, 15 of all 71 (21.1%) patients had cancers. Among 32 patients who didn’t 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), 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 from RPILD (OR= 0.543, P=0.008) or fatality (OR= 0.707, P=0.012), which was also demonstrated in subgroup analyses. In contrast to various risk factors for RPILD or mortality, anti-SAE antibodies might be conversely a protective factor in anti-MDA5+ patients.

Keywords

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

Subject

Medicine and Pharmacology, Clinical Medicine

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