Study finds new coronavirus infection linked to increase in autoimmune lung diseases

Recent e-biomedicine Studies have identified common immunopathology between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and viral infections. melanoma Differentiation-associated protein 5 (MDA5) autoimmunity.

study: MDA5 autoimmune and interstitial pneumonia (MIP-C) coinciding with the COVID-19 pandemic. Image credit: Light Studio Design / Shutterstock.com

background

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

Anti-Mi-2 targeting Mi-2 nuclear antigen, the first autoantibody associated with DM. Over time, multiple myositis-specific and related autoantibodies (MSAs) have been identified for different phenotypic patterns.

Clinically, myopathic dermatomyositis (CADM) is significantly associated with DM and causes progressive ILD. CADM is expressed through the retinoic acid-inducible gene 1 (RIG-1)-like receptor family gene IFIH1, which encodes the MDA5 protein.

A recent study highlighted that MDA5+ cases prior to the coronavirus disease 2019 (COVID-19) pandemic exhibited significant symptoms of ILD. However, these patients did not develop the classic DM solar rash, but instead developed skin-based clinical manifestations such as tender palmar papules and skin ulcers.

MDA5 is a RIG-1 helicase 12 that functions as an RNA sensor and pattern recognition receptor for SARS-CoV-2. Recent studies have revealed that variants in the IFIH1 gene confer protection against SARS-CoV-2 infection and promote favorable outcomes.

Therefore, to better understand the increased anti-MDA5 positivity rate during the COVID-19 pandemic, it is important to identify factors associated with MDA5+-related diseases.

About research

In the current study, we investigated the epidemiological factors that lead to MDA5+-related diseases. MDA5 autoimmunity with interstitial pneumonia (MIP-C), which coincided with the coronavirus disease (COVID-19) pandemic, was also investigated.

To this end, we used transcriptomic datasets to investigate the mechanisms shared between MDA5-related diseases and COVID-19. To better understand the causes of MDA5+ -DM development, we used transcriptomic datasets to compare autoimmune lung disease, acute COVID-19 lung disease, and idiopathic pulmonary fibrosis (IPF).

A model was developed that links severe antiviral cytokine responses to interferon-inducible helicase C-domain-containing protein 1 (IFIH1) stimulation, which is responsible for the unique immunophenotype associated with MSA-associated progressive ILD.

Data on the number of MDA5+ cases each year from January 2018 to December 2022 was collected from Leeds Teaching Hospitals NHS Trust, which acts as a reference for immunology laboratories in Yorkshire. The clinical records of the MDA5+ case showed a pattern of symptomatic MDA5 disease, particularly the extent of his ILD, treatment, treatment response, and survival.

Data from Public Health England (PHE) allowed researchers to quantify the monthly positivity rate for coronavirus infections in Yorkshire. Data on vaccination status and severity of lung infection in these patients were also obtained.

research result

The current study documents the characteristics and consequences of an upsurge in MDA5+ myositis or ILD during the COVID-19 pandemic in the UK, specifically in 2021.

Six new MDA5+ cases were confirmed from January 2018 to December 2019, indicating MSA immunoblot positivity rates of 1.2% and 0.4% in the respective years. However, after the second wave of COVID-19 infections, new MDA5+ cases increased rapidly. More specifically, the number of new infections in 2020, 2021, and 2022 was 9, 35, and 16, respectively. Therefore, the MDA5 positivity rate increased from 1.2% in 2018 to 1.7% in 2022.

Approximately 42% of MDA5+ cases were associated with progressive ILD, and approximately 33% showed progressive MDA5+-ILD. Both transcriptome dataset analysis and clinical epidemiological observations suggest that the surge in MDA5 autoimmunity and ILD during COVID-19 is a common aberrant type 1-centric IFN response rather than IPF. It was shown that this may be due to

Considering our findings and similar cases reported internationally, we proposed the terms MDA5 autoimmunity and MIP-C in this study. The advantage of this acronym lies in the distinct features that distinguish MIP-C from the syndrome of adult MDA5+ DM57. For example, the MIP-C phenotype has the following similarities: Multisystem inflammatory syndrome in children (MIS-C), even if the patient has no history of COVID-19 infection.

Approximately 42% of new cases had not been vaccinated prior to MDA5+ disease and represent a milder form of COVID-19 infection, which may be sufficient to cause MDA5 autoimmunity.

Immune responses or autoimmunity to MDA5 upon SARS-CoV-2 and/or vaccine exposure were assessed. This demonstrated a novel immunogenicity in non-immune subjects, when RNA binds to MDA5, increasing cytokine responses and inducing autoimmune diseases.

Theoretically, the development of herd immunity and reduced SARS-CoV-2 exposure could have contributed to milder symptoms in the MIP-C cohort. Taken together, activation of MDA5 protein by natural infection or vaccination may induce her MIP-C.

conclusion

Current transcriptome analysis reveals a possible causal relationship between the surge in anti-MDA5 positivity, COVID-19 infection, and autoimmune ILD. In the future, these findings should be validated using a cross-country, multicenter cohort.