Immunotherapy reversed myopathy but not cardiomyopathy in a necrotizing autoimmune myopathy patient with positive anti-SRP and MDA-5 autoantibodies

Abstract

Background Necrotizing autoimmune myopathy (NAM) is pathologically characterized by myofiber necrosis and regeneration with paucity or absence of inflammatory cells in muscle biopsy. Two autoantibodies, namely anti-signal recognition particle (SRP)-antibodies and anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)-antibodies, are typically specific with NAM. Anti-SRP-positive NAM can be associated with cardiomyopathy which responds well to immunotherapy. Here we reported an anti-SRP-antibody and anti-MDA5-antibody NAM patient who developed severe cardiomyopathy after gaining significant improvement of myopathy and subsequently accepted heart transplantation. Case presentation A NAM case with both positive anti-SRP and MDA-5 antibodies who gained significant improvement of the skeletal muscle weakness with immunotherapy, but 3 years later he developed severe dilated cardiomyopathy and at last received heart transplantation. Myocardial biopsy showed disarranged and atrophic myofibers, remarkable interstitial fibrosis without inflammatory infiltrates. Immunohistochemistry analysis revealed increased polyubiquitin-binding protein p62/SQSTM1 protein expression and the positive staining of cleaved-caspase 3 in a few cardiomyocytes. After the transplantation, the patient was symptom-free on oral prednisone (10 mg/day) and tacrolimus (2 mg/day). Conclusions We described the first case of anti-SRP and anti-MAD5 positive NAM who had received heart transplantation because of cardiopathy. Though the myopathy had been clinically improved after immunotherapy, the cardiomyopathy remained progressive and lethal. The processes of dysfunctional autophagy and augmented apoptosis were putatively pathophysiological mechanisms underlying cardiac damage in anti-SRP and anti-MAD5 positive NAM.

The Clinicopathological Distinction between Immune-Mediated Necrotizing Myopathy and Limb–Girdle Muscular Dystrophy R2: Key Points to Prevent Misdiagnosis

“…Myocardial abnormalities were frequently detected in both IMNM and LGMD R2, but no patient reported any cardiac symptoms. Cardiac involvement is a relatively common extramuscular manifestation of IMNM [ 14 ], associated with a poor prognosis of IMNM [ 15 , 16 ]. The dysferlin protein also presents in the myocardium, and its deficiency leads to myocardial injury [ 17 , 18 , 19 ].…”

Autoantibodies in the pathogenesis of idiopathic inflammatory myopathies: Does the endoplasmic reticulum stress response have a role?

“…The SRP auto-antigen might be an example of antigen released from tissue damage (159), a target of anti-SRP antibodies (160). It has been reported that auto-antibodies against SRP54 exist in IMNM and PM patients with dilated cardiomyopathy, disease severity, and remarkably high levels of muscle enzymes (160)(161)(162). One study of DM patients documented the presence of anti-SRP72 antibodies (163).…”

Anti-SRP immune-mediated necrotizing myopathy: A critical review of current concepts

“…There are some conflicting conclusions on cardiac involvement in SRP-IMNM. One case with SRP-IMNM was complicated by cardiomyopathy, gradually developed heart failure, and is ultimately relieved after heart transplantation ( 52 ). Some case reports and studies suggest that patients with SRP-IMNM are susceptible to subclinical myocardial damage ( 32 , 52 – 55 ).…”

“…One case with SRP-IMNM was complicated by cardiomyopathy, gradually developed heart failure, and is ultimately relieved after heart transplantation ( 52 ). Some case reports and studies suggest that patients with SRP-IMNM are susceptible to subclinical myocardial damage ( 32 , 52 – 55 ). Echocardiogram abnormalities usually appear in SRP-IMNM and account for 61% (25 of 41 patients), most presenting as diastolic dysfunction ( 32 ).…”

“…Generally, steroid monotherapy does not control the disease progression and most patients required additional immunosuppressants to achieve improvement in IMNM ( 4 , 6 , 7 , 81 ). A high recurrence risk by decreasing the dose of glucocorticoids is reported ( 25 , 32 , 52 ). Once dyspnea occurs in IMNM, intensive care and augmenting immunotherapy are required, including plasma exchange, cyclophosphamide, and/or cyclosporine ( 4 ).…”