The Significance of Heart-Reactive Antibodies in Heart Disease

T he controversy as to whether heart-reactive antibodies ( HRA ) are a cause on consequence of cardiac disease has not been settled. Those who favor a nonpathogenic role for antibodies point out that HRA occur commonly following myocandial infarction,1 cardiac surgery,2 and other noxious insults to the heart.3 These antibodies are observed usually ten days after injury and disappear in about six weeks.4 Attempts to demonstrate in vivo on in vitro cytotoxicity of HRA in animals have largely failed.5 6 Geny et al5 showed that rabbits immunized against homologous heart tissue produced HRA which were not cytotoxic to rabbit heart cells in vitro. On the other hand, hetenologous antibodies were sometimes cytotoxic.6 In contrast, circumstantial evidence does implicate the participation of HRA in certain forms of heart disease such as rheumatic 1 postmyocandial infarction (Dressier’s) 7 and postpericandiotomy syndrome.8 In rheumatic fever, HRA are found in 41 to 87 percent of patients with active canditis, but in lower incidence in those with inactive on questionable carditis.2’9 Following streptococcal infection, the incidence and titer of HRA were shown to be higher in those patients who would subsequently develop canditis.91#{176} In a small series of patients, recurrence of rheumatic fever was invariably associated with HRA.’#{176} In addition to the presence of circulating HRA, direct immunofluonescent studies of heart muscle from patients with rheumatic canditis have demonstrated immunoglobulin bound to myocandium.1’ The nature of eluted gamma globulin and whether it is complexed with specific antigen remains to be determined, and its potential role in pathogenesis of the canditis of rheumatic fever has not been clarified. An autoimmune mechanism involving cross-reaction between group A Streptococcus and human heart antigens is widely accepted. A specific antigenic component of the Streptococcus involved in these phenomena has yet to be identified. There is considenable debate as to the relative roles of the cell wall, cell membrane, or M-pnotein in the immune rnechanisms of rheumatic fever.’0’1’ Dressier’s syndrome is said to occur in less than 3 percent of patients after myocandial infarction. This sequela is frequently associated with HRA. Their occurrence coincides with clinical illness and disappears during quiescent periods.7 The rarity of Dresslen’s syndrome, the interval between infarction and onset of symptoms, the antibody response and its relation to clinical symptomatology, and the dramatic response of these patients to therapy with conticostenoids7 all suggest an autoimmune basis. HRA have also been observed in the postpericandiotomy syndrome. Engle et al8 showed that this syndrome may occur in as many as 30 percent of patients undergoing intrapenicardial surgery.8 HRA appeared at the end of the first week and coincided with the first clinical evidence of the syndrome. These authors,8 using the immunofluonescent technique, showed that all their patients had HRA. Furthenniore, sena from these patients possessed antibodies which stained heart tissue substrate more intensely than sera from patients who developed HRA but no postpenicandiotomy syndrome. There is increasing evidence that HRA may play an important role in the rejection episodes which follow cardiac transplantation. Zabniskie et al’3 found that clinical rejection correlated closely with a rise in the serum level of HRA. Treatment with immunosuppressive agents resulted in a decrease in HRA and an improved clinical condition. Rarely was a rise in HRA the only clue to cardiac rejection. Rossen et found little evidence of immunoglobuun deposits in hearts removed from patients undergoing transplantation, even though most of their recipients had circulating HRA. At necropsy, however, immunogiobulins were shown to be bound to sancolemma and muscle fibers and were deposited in the intima and media of the coronary arteries of the allognafts. The extent of these deposits seemed to correlate with the number of episodes of rejection and length of survival. Goldman et al’5 also showed HRA in sena iii a transplant model in dogs and extensive, bound immunoglobulins in the rejected donor hearts. As evidence that the fixed gamma