Postinfectious Autoimmunity: Two Distinct Phases of Coxsackievirus B3‐Induced Myocarditis a

An encounter between an infectious agent and a host involves a complex of interactions that may or may not lead to disease. The genetic composition of both the host and the infectious agent will determine the extent of the initial infection and the severity of the resulting pathology. The immune response toward the invading pathogen is the major host mechanism affecting the severity both of the infection and of the resultant disease and in limiting subsequent infections. The immune response, however, can play a paradoxical role by leading to exacerbation of disease rather than promoting recovery. A wide variety of viruses has been shown to produce myocarditis in man.’ The most common are the R N A viruses of the Picornavirus,24 Orthomyx~virus ,~ Paramyxovirus,6 Togavirus,’ Rhabdovirus: and Arenavirus’ families. The most common of these viruses, the Coxsackievirus B group, is associated with about half of the clinical cases of infectious myocarditis.’”” Of this group, Coxsackievirus B, (CB,) induces the highest incidence of myocardial disease.12 Usually, the association of this virus with cardiac disease is inferred from serological studies since isolation and identification of the virus itself has been difficult. The diagnosis of myocardiopathy often requires endomyocardial biopsy.13 The principal drawbacks of this diagnostic method are the focal nature of the inflammatory cellular infiltrate and the lack of universally accepted guidelines for histologic assessment. 14,’ Several pathogenetic mechanisms have been proposed to account for virus-induced myocardiopathy.’.1”18 Since CB, is a lytic virus, one plausible mechanism is direct injury to the myofibers. In addition, myocardial tissue injury can be correlated with the severity of the inflammatory lesions, suggesting that inflammation itself may be responsible for the injury. On the other hand, a protective effect has been associated with the inflammatory response.1gs20 Treatment of mice with cor t icos te r~ ids~~ and cyclophosphamideZ0 to reduce inflammation caused more severe disease. During the last decade, several lines of evidence have pointed to autoimmunity as a cause of myocarditis. Maisch and his colleagues’* have described heart-specific autoantibodies in patients with infectious myocarditis. These antibodies were found to mediate myocyte lysis by complement,21 as well as cell-mediated antibody-dependent cytotoxicity.22 In a murine model using BALB/c mice, Woodruff and his colleagues’*23 and