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Idiopathic inflammatory myopathies (IIM) involve chronic inflammation of skeletal muscle and subsequent muscle degeneration due to an uncontrolled autoimmune response; however, the mechanisms leading to pathogenesis are not well understood. A compromised sarcolemmal repair process could promote an aberrant exposure of intramuscular antigens with the subsequent initiation of an inflammatory response that contributes to IIM. Using an adoptive transfer mouse model of IIM, we show that sarcolemmal repair is significantly compromised in distal skeletal muscle in the absence of inflammation. We identified autoantibodies against TRIM72 (also known as MG53), a muscle-enriched membrane repair protein, in IIM patient sera and in our mouse model of IIM by ELISA. We found that patient sera with elevated levels of TRIM72 autoantibodies suppress sarcolemmal resealing in healthy skeletal muscle, and depletion of TRIM72 antibodies from these same serum samples rescues sarcolemmal repair capacity. Autoantibodies targeting TRIM72 lead to skeletal muscle fibers with compromised membrane barrier function, providing a continuous source of autoantigens to promote autoimmunity and further amplifying humoral responses. These findings reveal a potential pathogenic mechanism that acts as a feedback loop contributing to the progression of IIM.

The authors report a 44-year-old man with rippling muscle disease (RMD) who does not have a mutation in the caveolin-3 gene. Immunohistochemistry of the muscle biopsy revealed a marked reduction of caveolin-3 and a mosaic pattern of dysferlin immunostaining. Ultrastructural studies showed a loss of caveolae and alterations of the triad. Autoantibodies were directed against the sarcolemma, triad, and several unknown muscle proteins.

Objective: An autoimmunological approach to the pathogenesis of post-pericardiotomy syndrome., Methods: In 100 consecutive patients, after open heart surgery, postpericardiotomy syndrome (PPS) was diagnosed in 15 patients according to clinical and laboratory criteria. These patients were prospectively followed up. Levels of serum autoantibodies against cardiac muscle antigen were studied on the 14th, 21st and 33rd day postoperatively. In order to evaluate the cardiac muscle antibody (CMA), antigenic tissue sections from primate heart tissue in solid phase with intermyofibrillar and sarcolemmal-subsarcolemmal fluorescent staining, were taken as substrate. PPS occurrence was determined according to strongly positive antibody titers on the 14th and 21st day postoperatively., Results: CMA were positive in 18 patients, and 14 of them showed clinical signs of PPS. In one case PPS was apparent clinically although CMA were not detected. There was a significant difference between CMA positive and CMA negative patients on the occurrence of PPS. With the use of monoclonal antihuman IgG in the conjugate of indirect fluorescent antibody test the specificity was enhanced. Also, in our experience, the length of cardiopulmonary bypass (CPB) time was an important factor affecting the development of PPS., Conclusion: In this study, we found a positive correlation between the presence of CMA and PPS, which is a practical, secure and cheap criterion for the diagnosis.

We have previously reported that B10.A (H-2a) mice, which are resistant to the induction of postcoxsackievirus autoimmune myocarditis, become susceptible upon treatment with LPS, IL-1, or TNF. In this study, we show that the development of autoimmune myocarditis is associated with infiltration of the heart by inflammatory cells that secrete the cytokines IL-1 and TNF. Local secretion of these cytokines contributes to increased levels of IL-1 and TNF in the serum. Thus, local production of cytokines promotes the induction of this postinfectious autoimmune disease.

Cardiac-specific autoantibodies to sarcolemmal and cardiac myosin antigens observed during the chronic phase of Coxsackievirus B3-induced myocarditis appear to be under autosomal recessive control. This observation is based on examination of F1 hybrids bred from A/J mice which develop chronic myocarditis and C57BL/6J mice which resolve the virus-induced lesions. Previous mouse studies demonstrated that the prevalence of heart-specific autoantibodies varied with the H-2 complex. However, in 25 H-2 congenic mouse strains the strain background was the predominant determinant of autoantibody presence. Recently, we extended our genetic evaluation of the chromosomal locations governing autoantibody responses by examining 25 AXB and BXA recombinant inbred strains. Two populations of heart-specific autoantibodies were demonstrated against sarcolemmal and cardiac myosin antigens. Analyses of the AXB/BXA strain distribution patterns for these two traits revealed that the anti-sarcolemmal response was controlled by a gene(s) linked to Np-2 and Ter alpha loci on chromosome 14. Linkage could not be assigned for the anti-cardiac myosin response.

We report the clinical and serological studies in patients who underwent pericardiotomy. Seventy three per cent of them developed antisarcolemma antibodies 4 weeks after surgery, and a third of them also had antimitochondrial antibodies. However, clinical post-pericardiotomy syndrome was rare; only 7% of the patients fulfilled the criteria for this diagnosis. Although immune responses against tissue antigens are frequent as a consequence of surgical trauma, the clinical manifestations are rare.

Anti-virus-antibodies are elevated in a relatively high number of dilated cardiomyopathies, and in myocarditis increasing or decreasing titers can characteristically be observed. In myocarditis as well as in dilated cardiomyopathy the high incidence of antibodies in the serum of the patients against myocardial sarcolemmal and mitochondrial proteins coincides with a low T-cell-suppressor activity. T-lymphocyte-cell-suppressor activity modifies the immunoglobulin synthesis of B-lymphocytes. The T-cell-suppressor activity has been found to be low in myocarditis as well as in congestive cardiomyopathies. This coincidence looks like a pathogenetic link, since a low T-cell-suppressor activity is generally correlated to an increased antibody synthesis of B-lymphocytes. The finding of a low T-cell-suppressor activity in a small group of normal individuals supports the concept that this group has a predisposition to suffer from myocarditis and later on developing dilated cardiomyopathy. Thus there are several indicators of a probably genetically determined immunological defects which can play a pathogenetic role in the development from myocarditis to dilated cardiomyopathy.