Association of Cytomegalovirus Infection With Anti-MDA5 Antibody-Positive Dermatomyositis: A Prospective Cohort Study

Abstract

Objectives: To investigate whether cytomegalovirus (CMV) infection plays a role in the pathogenesis and prognosis of idiopathic inflammatory myopathy (IIM), particularly in anti-MDA5 antibody-positive (anti-MDA5+) dermatomyositis (DM).Methods: A prospective cohort of 204 newly diagnosed IIM patients and 50 healthy individuals were enrolled in the study. CMV-IgM and CMV-IgG antibody concentrations and lymphocyte counts were analyzed. Differences in categorical data were compared using Fisher's exact test and the chi-square test. One-year survival rates were analyzed in MDA5+ DM patients with and without CMV infection.Results: In IIM patients, the median CMV-IgM level was significantly higher than in healthy controls (6 U/mL vs. 0 U/mL, p < 0.05) as was the median CMV-IgG level (114 U/mL vs. 105 U/mL, p < 0.05). The percentage of recent CMV infections in the MDA5+ DM group was much higher than it was in the MDA5− IIM group (19.1% vs. 7.0%, p = 0.009). MDA5+ DM patients with CMV DNA-emia had poorer 1 year survival than the CMV-DNA− group (33.3% vs. 86.3%, p = 0.010). CMV-IgM-positive (CMV-IgM+) MDA5+ DM patients had lower CD4+ T cell counts (245.7 cells/μL vs. 420.5 cells/μL, p < 0.05) and CD19+ B cell counts (97.3 cells/μL vs. 240.6 cells/μL, p < 0.05).Conclusion: The number of CMV infections was significantly higher in IIM patients, particularly in MDA5+ DM patients. Lower CD4+ T cells and CD19+ B cells were observed in CMV-IgM+ MDA5+ DM patients. CMV infection may have an important role in the pathogenesis and prognosis of MDA5+ DM by disrupting immunity.

Application value of blood metagenomic next-generation sequencing in patients with connective tissue diseases

“…Huang et al. reported that CMV infections were significantly higher in idiopathic inflammatory myopathy patients, particularly in MDA5+ DM patients, and suggested that CMV might participate in the pathogenesis of MDA5+ DM by decreasing CD4+ T cells and CD19+ B cells ( 4 ). Our previous studies have also reported the high incidence of EBV and CMV infections, and found that the Th17 and Treg levels were decreased in the SLE patients with EBV or CMV viremia ( 32 ).…”

“…The fatality rate of CTD such as systemic lupus erythematosus and dermatomyositis is high and there is no current cure. The main therapeutic strategies are glucocorticoids and immunosuppressive drugs, but the effects are not satisfactory and the side effects are obvious, leading to the increase of infection ( 2 – 4 ). Autoimmune disorders and treatments give rise to susceptibility for infections in CTD, it is reported that the risk of opportunistic infection was highest for dermatomyositis and polymyositis/dermatomyositis (DM/PM), followed by systemic lupus erythematosus (SLE) ( 2 , 5 ).…”

Anti-MDA5 dermatomyositis after COVID-19 vaccination: a case-based review

“…Viral infection has long been thought to be a potential etiology for autoimmune disease, including IIM [ 1 , 3 , 12 , 27 ]. Development of autoimmune reaction following SARS-CoV-2 infection (including IIM) has been described extensively and the similarities with anti-MDA5 disease and COVID-19 infection have further increased this suspicion [ 1 , 2 , 4 , 12 – 15 , 28 – 35 ].…”

“…This sets the tone for the suggestion that the production of anti-MDA5 antibodies during virus infection, including COVID-19, is an epiphenomenon associated with the onset of CADM and RP-ILD; namely, infection of the skin and lung epithelium that may up-regulate the expression of MDA5 in the infected tissues [ 1 – 3 , 17 , 36 , 39 ]. The possible mechanisms of autoimmunity may be molecular mimicry, or the virus itself may activate antigen-presenting cells directly, activation of T-cells, and consequent cytokine storm with resultant tissue damage [ 13 , 27 ]. This can further be favored by specific genetic variants predisposing individuals to loss of tolerance of the MDA5 antigen resulting in the production of anti-MDA5 autoantibodies [ 3 , 39 , 40 ].…”

“…It is also shown that Pangolins, the natural reservoir of COVID-19 lack the MDA5 gene, possibly providing them an evolutionary advantage [ 43 ]. Autoimmunity and immunodeficiency occur along a continuum, and the frequent occurrence of viral infections in patients with anti-MDA5 positive myositis raises the case for deregulated viral clearance due to polymorphisms in viral sensors [ 27 , 44 ]. Besides, occasional reports of psoriasiform rashes and cutaneous features in patients with anti-MDA5 positive IIM, when such rashes are otherwise described in those with MDA5 mutations suggest that our current understanding of this disease may be just the tip of the iceberg, with several undiagnosed forms currently misunderstood in the absence of a timely genetic and autoimmune screen [ 45 ].…”