Response by Antibodies to Tissue Antigens in the Course of Rheumatic Fever

Weintraud (1913) was the first to envisage the possibility that tissue alterations in rheumatic patients may be due to a pathogenic anaphylactic reaction, but at that time it was not possible to verify his hypothesis by laboratory tests. The toxic properties of sera from rheumatic fever patients were first experimentally demonstrated by Ramsdell and Davidsohn (1930), and Klujeva and Bobritzkaja (1934). Brokman, Brill, and Frendzel (1937) found in the sera of rheumatic patients antibodies which gave a complement-fixation reaction with organs from children who had died with rheumatism. Coburn and Pauli (1939) found in the sera of patients in the acute stage of rheumatic fever a precipitin which reacted to an antigen which had been present in the blood before the onset of the attack. Their findings were partially corroborated by Wedum and Wedum (1946), but were questioned by Fischel and Pauli (1949). Auto-antibodies to an aqueous extract of myocardium were demonstrated by Cavelti (1945) by means of collodion particle agglutination in a high proportion of rheumatic fever cases. Lippman, Cameron, and Campbell (1950) detected them in the sera of nephritic patients and proved their cytotic effects on myocardial tissue cultures. Lansbury, Crosby, and Bello (1950) found in the sera of patients with rheumatoid arthritis antibodies which would bind with extracts from pathological and normal tissues. Rejholec, Vancura, Wagner, and Mandlikova (1952) demonstrated antibody to myocardium in the blood of nephritic patients by means of collodion particle agglutination; Rejholec, Wagner, and Mandlikova (1952) and Rejholec and Wagner (1955) also showed them by the same method in patients with rheumatic fever. Osler, Hardy, and Sharp (1954), using alcoholic extract of human heart for antigen, observed complement-fixation reactions in 50 per cent. of rheumatic patients, but also in 20 per cent. of controls. Vorlaender (1952), and Vorlaender, Fitting, and Blankenheim (1954) demonstrated auto-antibodies in several patients with rheumatic fever by the technique of absorption and haemagglutination of erythrocytes sensitized with artery-wall antigen. They observed a certain parallelism with the course of the disease, although the number of their cases was small. Their findings were positive in the subchronic stage of the disease and negative in the acute phase. Steffen (1954a, b), Steffen and Rosak (1955), and Steffen and Schindler (1955) developed an indirect serological method of demonstrating auto-antibodies to connective tissue in rheumatism by absorbing the antiglobulin serum. On the other hand, Fischel and Pauli (1949) failed to find antibody in rheumatism by the technique of collodion particle agglutination. It should be noted that Cavelti himself and subsequent investigators (McKee and Swineford, 1951; Peck and Thomas, 1948; Humphrey, 1948) were unable to repeat his work. The present investigation was undertaken to verify the finding of auto-antibodies in the course of rheumatic fever, and to establish whether there is an interdependence between the clinically demonstrable involvement of different organs and tissues and the occurrence of antibody, and whether the presence and the level of auto-antibodies may serve as an index of disease activity. Blood samples were tested at short intervals during periods of hospitalization for the presence of antibodies to five types of tissue. The results were then compared with parallel clinical observations.