Anti-MDA5 autoantibodies predict clinical dynamics of dermatomyositis following SARS-CoV-2 mRNA vaccination: a retrospective statistical analysis of case reports

Abstract

Since the introduction of mRNA vaccines against SARS-CoV-2, the induction of autoimmunity by mRNA vaccination has been discussed. Several cases of dermatomyositis (DM) associated with mRNA vaccination against SARS-CoV-2 infection have been reported. The question is whether there is a common pathomechanism for the induction of DM by this mRNA vaccination. The aim of this review is to analyse the sample of previously published case reports of DM following COVID-19 mRNA vaccination for common indicators of a possible immune pathomechanism.In this review, we summarised case reports of DM following mRNA vaccination against COVID-19. We considered this case report landscape as a cumulative sample (n = 32) and identified common clinical and molecular parameters in the intersection of case reports and statistically analysed the effect of these parameters on the development of DM.MDA-5 antibodies seem to play a role in the autoantibody signature after mRNA vaccination. MDA-5-positive DM is statistically more strongly associated with mRNA vaccination and interstitial lung disease/rapidly progressive interstitial lung disease (ILD/RP-ILD) than MDA-5-negative DM. MDA-5-positive DM seems not to be associated with an increased risk of malignancy, whereas MDA-5-negative DM is more strongly associated with malignancy.Our findings emphasize the potential role of innate antiviral signalling pathways in connecting DM to mRNA vaccination. MDA-5 autoantibodies appear to be predictive of a severe DM progression following mRNA vaccination. There seems to be an association between MDA-5 autoantibodies and paraneoplastic DM post-vaccination. Further studies are required to uncover the underlying mechanisms of autoimmunity triggered by mRNA vaccination.

Keywords: Autoimmunity; COVID-19; Case report; Dermatomyositis; MDA-5; mRNA vaccination.

Fig. 1

PRISMA flow diagram (Status of the literature search: 07/2024): dermatomyositis following SARS-CoV-2 mRNA vaccination

Fig. 2

General characteristics of the case report landscape. A: Age distribution of the discussed case reports on dermatomyositis following mRNA vaccination. B: Absolute incidence of case reports of on dermatomyositis following mRNA vaccination by sex. C: Number of mRNA vaccinations before symptom onset of dermatomyositis. D: Number of pre-existing conditions in patients in the case report sample. If pre-existing conditions were not reported in the case reports, these patients were not included in the presentation

Fig. 3

Clinical results. A: Relative frequency of DM-typical symptoms. 1: Shawl sign, 2: Gottron papules, 3: Lack of strength/Weakness, 4: Heliotropic erythema, 5: Muscular pain, 6: Periungual erythema, 7: Dysphagia, 8: Dyspnea, 9: Fever, 10: Fatigue, 11: Weight loss. Other DM-typical symptoms were reported less regularly, so they could not be included in our analysis. B: Frequency of DM-typical symptoms (Shawl sign, Gottron papules, Lack of strength/Weakness, Heliotropic erythema, Muscular pain, Periungual erythema, Dysphagia, Dyspnea, Fever, Fatigue, Weight loss). C: Proportion of patients with interstitial lung disease/rapidly progressive interstitial lung disease (ILD/RP-ILD) on the sample of all case reports. D: DM-typical symptoms in patients with and without reported ILD, respectively. Case reports that did not report ILD were assumed not to have been diagnosed with ILD. E: Number of patients with dyspnea at initial diagnosis arranged by occurrence of ILD/RP-ILD during progression. F: CK levels [U/L] in all case reports (17 of 32 cases) that explicitly documented CK laboratory results. When CK kinetics were reported, the maximum CK value was considered here

Fig. 4

Autoantibody signature after mRNA vaccination and the special role of anti-MDA-5 antibodies. A: Relative frequency of Autoantibodies. 1: Antinuclear antibodies (ANA), 2: Anti-Melanoma differentiation-associated protein 5 (MDA-5), 3: Anti-Transcriptional intermediary factor-1γ (TIF-1γ), 4: Sjögren’s-syndrome-related antigen A autoantibodies (SSA(Ro)), 5: Anti-Nucleosome Remodeling Deacetylase complex (Mi-2/ NuRD), 6: Anti-Extractable nuclear antigen (ENA), 7: Anti-Nuclear matrix protein-2 (NXP2), 8: Rheumatoid factor (RF), 9: Anti-Small ubiquitin-like modifier 1-activating enzyme (SAE-1), 10: Cyclic citrullinated peptides (CCP), 11: Anti-Juvenile dermatomyositis antigen (jDM), 12: Anti-Ribonucleoprotein (RNP), 13: Anti-Signal recognition particle (SRP), 14: Anti-Polymyositis/Scleroderma (75 kDa) antigen (PM/Scl75), 15: Anti-Polymyositis/Scleroderma (100 kDa) antigen PM/Scl100, 16: Anti-threonyl-tRNA synthetase (PL-7), 17: Anti-alanyl-tRNA synthetase (PL-12). Other autoantibodies have not been detected. ENA sums the presence of autoantibodies SSA (Ro), Anti-Soluble Substance B-antigen (SSB (La), Anti-Ribonucleoprotein (RNP), Anti- Smith antigen (Sm), Anti- Topoisomerase I (Scl-70), Anti- Histidyl–tRNA synthetase (Jo-1). B: Distribution of latency in days between last mRNA vaccination and first appearance of dermatomyositis-specific symptoms. C: MDA-5-positive dermatomyositis: Distribution of latency in days between last mRNA vaccination and first appearance of dermatomyositis-specific symptoms. D: MDA-5-negative DM: Distribution of latency in days between last mRNA vaccination and first appearance of dermatomyositis-specific symptoms. E: Interstitial lung disease/rapidly progressive interstitial lung disease ILD/RP-ILD depending on the presence of MDA-5 autoantibodies. F: Four-way table for the detection of anti-MDA-5 autoantibodies (MDA5+/-) and the detection of cancer in the case of successful cancer screening (Cancer+/-). The absolute frequencies of the sample are given, in brackets the relative frequencies based on n = 32