Studies of Hemolytic Streptococcal Antibodies in Control Groups, Rheumatic Fever, and Rheumatoid Arthritis
Authors: Mote John R. , Jones T. Duckett 
Published: January 2023

General Summary
The data presented have concerned scarlet fever, hemolytic streptococcal respiratory-tract infections, and primary and recurrent rheumatic fever in previously inactive rheumatic subjects. The rheumatic-fever data have been limited to those previously in the inactive phase of the disease because the clinical evaluation of changes in the severity of this frequently cyclic or chronic disease is difficult. Furthermore, the evaluation of the significance of minor variations in the titer of antibodies is difficult and often questionable in active rheumatic subjects who usually have hemolytic streptococcal antibodies in their blood, frequently in high concentration.
In the presentation of the results and for the purpose of discussion, the several types of antibodies have been considered specific for hemolytic streptococcal infection although this may not be entirely true. In our own experience antistreptolysin “O” has been specific for the hemolytic streptococcal infections because it usually increases during convalescence from hemolytic streptococcal infections and in no instance has it been seen to increase in titer in an individual where infection by the hemolytic streptococcus could be completely excluded from consideration. In the analyses which have been presented in this study, emphasis has been placed chiefly on the antistreptolysin “O” titers because of its relative specificity and because it is the only one of the several types of antibodies tested that can be titrated with any accuracy in human blood serum. Next in order of specificity and emphasis has been antifibrinolysin, which in our experience has been specific for hemolytic streptococcal fibrinolysin. Boisvert (3) has reported the plasmas of patients in the febrile phase of pneumonia resistant to lysis by fibrinolysin, an observation which we have corroborated. However, with this possible exception, our experience has been that the appearance of antifibrinolysin in the blood is usually associated with infection by the hemolytic streptococcus. Less emphasis is placed on this antibody in the discussion of results, however, for reasons that have been discussed in detail in the first of this group of papers. The major inadequacy of this test as performed is that it is a qualitative rather than a quantitative measure of antifibrinolysin. Little emphasis has been placed on the presence or appearance of precipitins in the discussion of the analytic results for reasons that were fully considered in the first paper of this series. Briefly, these may be reviewed by stating that 1) the precipitins to the several hemolytic streptococcal products used are not specific for hemolytic streptococcal infections, with the exception of the “C” fraction precipitins; 2) the tests as performed are not quantitative measures of antibody; and 3) the high incidence of precipitins in control groups renders the interpretation of their presence or appearance in the sera of patients difficult to evaluate and of questionable significance.
In summary, it is our experience and opinion that the presence of antistreptolysin “O” or antifibrinolysin (with the possible exception noted by Boisvert) in significant concentrations in the blood of a patient suggests that the patient has had one or more clinical or sub-clinical hemolytic streptococcal infections in the recent past, but it gives no index as to the character, the number, or the time—within a year or more—that these infections occurred.
Antistreptolysin “S” has not been considered because there was no practical technic for measuring it in human serum at the time the study was undertaken. Likewise, the presence of typespecific “M” precipitins were not determined because the general character of the study made it difficult, if not impossible, to evaluate the significance of their presence in blood sera.
With the above brief summary of the probable specificity and significance of the several antibodies tested in mind, the results of the several analyses will be summarily reviewed.
The data presented indicate that about 90 per cent of non-rheumatic individuals develop antibodies—frequently in high concentration—to one or more of the hemolytic streptococcal products tested at some time during their convalescence from hemolytic streptococcal infections. Furthermore, these antibodies can be detected in the blood for considerable periods of time—in some instances for months—subsequent to both clinically uncomplicated infections and to the more severe infections with complications. A detailed analysis of the antistreptolysin “O” data in a number of these infections failed to reveal any type of antistreptolysin “O” curve that can be considered characteristic of hemolytic streptococcal infections in non-rheumatic subjects. In general the titers are delayed in rising in the infections with complications and are slower in returning to normal than is the case in the uncomplicated illnesses, but in both the mild and the severe infections every type of antistreptolysin “O” curve has been encountered.
Analyses of similarly collected data from 87 primary attacks of rheumatic fever have revealed equally high incidence (90 per cent) of hemolytic streptococcal antibodies—usually in high concentration—at some time during the rheumatic illness whether there was or was not a history of a preceding or an associated respiratory infection.
Comparably collected data of the 179 rheumatic-fever recurrences in this study similarly analyzed in relation to the occurrence and the magnitude of a hemolytic streptococcal antibody-response revealed that in most instances (73 per cent) antibodies to one or more of the streptococcal products tested appeared in the blood during the illness—often in high concentration. It was further found that these antibodies persisted in the majority of the patients for months after the onset of their infection, but finally returned to normal levels even in the face of continuously, and often severe or even fatal, active rheumatic infection.
Differences between the results of the rheumatic and the non-rheumatic groups appear to suggest that mild or even moderately severe recurrent rheumatic fever may occasionally take place in inactive rheumatic subjects without detectable clinical or serological evidence of a preceding or an associated hemolytic streptococcal infection. This, however, does not exclude associated invasion by the hemolytic streptococcus because we have evidence in unpublished data that there are both sub-clinical and sub-immunological invasions by this organism in so far as the antibodies studied are concerned. Obviously important in the evaluation of the rôle of this organism in rheumatic fever are the hemolytic streptococcal infections that are not associated with recurrent rheumatic fever in known rheumatic subjects. This group of infections deserves further detailed investigation in order properly to orient the part played by the hemolytic streptococcus in rheumatic fever.
In our opinion, none of the analyses, including a detailed examination of the antistreptolysin “O” curves in both rheumatic and non-rheumatic subjects, have revealed any basic difference in the hemolytic streptococcal antibody-response, in so far as the antibodies investigated are concerned, between the non-rheumatic and the rheumatic individual in their reaction to infection by the hemolytic streptococcus.
The data in this study are interpreted to indicate that hemolytic streptococcal infections are important factors in rheumatic fever. However, whether or not they are the only factors involved must remain unanswered for the present. It is concluded that the mechanism responsible for producing rheumatic fever is as yet unexplained.