COVID-19 linked to rise in autoimmune lung disease, study finds – News-Medical.Net

A recenteBioMedicinestudy identifies shared immunopathology between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and melanoma differentiation-associated protein-5 (MDA5) autoimmunity.

Study:MDA5-autoimmunity and interstitial pneumonitis contemporaneous with the COVID-19 pandemic (MIP-C). Image Credit: Light Studio Design / Shutterstock.com

Dermatomyositis (DM) is an autoimmune diseasethatischaracterizedby severe skin and muscle inflammation. Additionally, DM is associated with interstitial lung disease (ILD),whichcauses progressive pulmonary fibrosis.

Anti-Mi-2, which targets the Mi-2 nuclear antigen, is the first autoantibody to be associated with DM. Over time, multiple myositis-specific and related autoantibodies (MSA) havebeen identifiedfor different phenotypic patterns.

Clinically, amyopathicdermatomyositis (CADM) has been significantly associated with DM and leads to progressive ILD. CADMis expressedthrough retinoic acid-inducible gene 1 (RIG-1)-like receptor family gene, IFIH1, which encodes the MDA5 protein.

A recent study highlighted that MDA5+ cases predating the coronavirus disease 2019 (COVID-19) pandemic exhibited a significant manifestation of ILD. However, these patients did not develop the classical DM heliotropic rash and instead developed skin-based clinical symptoms, includingtender palmar papules and skin ulceration.

MDA5 is a RIG-1 helicase12 thatfunctions asan RNA sensor and pattern recognition receptor for SARS-CoV-2. A recent study revealed that variants of the IFIH1 gene confer protection against SARS-CoV-2 infections and facilitate favorable outcomes.

Thus, it isvitalto identify the factors associated with MDA5+-related disease to better understand the rise in anti-MDA5 positivity during the COVID-19 pandemic.

The current study investigated the epidemiological factors that cause MDA5+ related disease. MDA5 autoimmunity with interstitial pneumonitis cotemporaneous with the COVID-19 pandemic (MIP-C) was also investigated.

To this end, transcriptomic datasets were usedto explore the mechanismsthataresharedbetween MDA5-associated disease and COVID-19. Transcriptomic datasets were also usedto compare autoimmune lung disease, acute COVID-19 lung disease, and idiopathic pulmonary fibrosis (IPF)to better understand the origin of the MDA5+ -DM outbreak.

A modelwas developedthat connected severe anti-viral cytokine response with interferon-induced helicase C domain-containing protein 1 (IFIH1) stimulation, which is responsible for the unique immunophenotype linked with MSA-associated progressive ILD.

Data on the number ofMDA5+ cases each year between January 2018 and December 2022 was collectedfrom theLeeds Teaching Hospitals NHS Trust, which serves as an immunology laboratory reference for Yorkshire.Clinical notes for MDA5+ cases indicated patterns of symptomatic MDA5 disease, particularly the degree of ILD, treatment, therapy responses, and survival rates.

Public Health England (PHE) data allowed the researchers to quantifymonthly COVID-19 positivity ratesin Yorkshire.Data on these patients' vaccination status and severity of lung infection were also obtained.

The current study documents the features and outcomes of the surge in MDA5+ myositis or ILDthat occurredduring the COVID-19 pandemic in the United Kingdom, especially in 2021.

Six new MDA5+ cases were identified between January 2018 and December 2019, which indicates 1.2% and 0.4% MSA immunoblot positivity in the respective years. However, after the second COVID-19 wave, there was a rapid increaseinnew MDA5+ cases. More specifically, the number of new cases in 2020, 2021, and 2022 were nine, 35, and 16, respectively; therefore, therate of MDA5 positivity increased from 1.2% in 2018 to 1.7% in 2022.

Approximately 42% of MDA5+ cases were associated with progressive ILD, with about 33% exhibiting aggressive MDA5+-ILD. Both transcriptomic dataset analysis andclinical epidemiologic observations indicated that the surge in MDA5 autoimmunity and ILD during COVID-19 could be due to shared aberrant type 1-centric IFN responses but not IPF.

Considering thestudy findings and similar cases reported internationally, the current study proposed the terms MDA5-autoimmunity and MIP-C.The merit of this acronym lies in the distinct features that can separate MIP-C from the syndrome of adult MDA5+ DM57.For example, the MIP-C phenotypehas similaritiesto multisystem inflammatory syndrome in children(MIS-C), evenin somecaseswhere the patient did not have a history of COVID-19.

About 42% of new caseswere not vaccinatedbefore MDA5+ diseaseand represented milder COVID-19 infection, which could be sufficient to cause MDA5 autoimmunity.

An immune reaction or autoimmunity against MDA5 upon SARS-CoV-2and/orvaccine exposure was assessed.Thisindicated novel immunogenicity in non-immune subjects upon RNA engagement with MDA5 that increased cytokine response and induced autoimmune disease.

Theoretically, the development of herd immunity and reduced SARS-CoV-2 exposure contributed to milder symptoms in the MIP-C cohort.Taken together, MDA5 proteinactivation through natural infection orvaccination can potentially induce MIP-C.

The current transcriptomic analysis elucidated the possible causal link between the surge in anti-MDA5-positivity, COVID-19, and autoimmune ILD. In the future, these findings mustbe validatedusing multicenter cohorts across nations.

Journal reference:

Excerpt from:

COVID-19 linked to rise in autoimmune lung disease, study finds - News-Medical.Net