Cold Agglutinins. Ii. Cold Isohemagglutinins in Primary Atypical Pneumonia of Unknown Etiology With a Note on the Occurrence of Hemolytic Anemia in These Cases

Abstract

In the preceding paper ( 1), there was presented a summary of the maximum titers of cold agglutinins found in 1069 cases of a variety of conditions, including the various infections of the respiratory tract that are commonly encountered in this vicinity. Significant titers (in dilutions greater than 20) were Methods. The method used in the tests for cold agglutins was given in detail in the preceding paper (1). For the present study, the specimens of venous blood were all collected under sterile precautions and the serum was separated from the clotted blood, either at room tempera-1 Hereafter referred to for brevity as "atypical pneumonia." ture or, more often, after the blood had been kept at 370 C. for a short while. The cleared sera were stored in rubber stoppered tubes at 5 to 100 C. Specimens, averaging 3 per patient, were obtained at suitable intervals. The tests were carried out either on the day when the blood was obtained or within a few days. Equal volumes of serum and 2 per cent saline suspensions of 2-to 4-day-old red blood cells from individual group 0 donors were used. The titers are recorded as the reciprocals of the highest final dilutions of serum giving 1 + agglutination at 0 to 50 C. and complete dispersion at 370 C. RESULTSThe conditions under which the present cases were studied unfortunately did not permit frequent observations throughout the entire course of the acute illness and prolonged observations during convalescence in every instance. Data concerning certain of the features to be considered are, therefore, based on limited numbers of cases. In the analysis which follows, the time relationships are referred to the day of onset of symptoms. In most of the cases, this could be ascertained quite accurately, but, in a few instances, it was only approximated. Time of appearance, decline, and disappearanceThe first postitive tests ( Figure 1A) were observed between the seventh and twenty-seventh days, but mostly during the second or third week. The last negative tests in the same cases were obtained before the end of the second week in all but 2 of them. The maximum titers (Figure 2) occurred mostly between the eleventh and twentyfourth days. There were a number of cases, however, in which the maximum titers were not attained until the fifth week or later, and in 4 cases, maximum titers of 40 to 160 were observed between the fourth and eighth days and lower titers obtained later. There was no definite correlation between the maximum titers and the time 458

Fluorescent-Stainable Antibodies to the Eaton Agent in Human Primary Atypical Pneumonia Transmission Studies*

“…Interpretation of the data is complicated by the present lack of knowledge of the nature of these fluorescent-stainable antibodies. Patients with primary atypical pneumonia may develop a variety of abnormal serologic reactions during convalescence: agglutinins for group 0 erythrocytes in the cold; agglutinins for streptococcus MG; complement-fixing reactions for various heterologous tissue antigens; and even false serologic tests for syphilis (8)(9)(10)(11)(12)(13)(14)(15). Liu and associates, by means of cross-absorption experiments, demonstrated that the fluorescent-stainable antibodies are distinct from cold hemagglutinins and streptococcus MG agglutinins (5).…”

“…Using a modification of the fluorescent antibody technique of Coons and Kaplan (4), Liu, Eaton and Heyl have provided both a means of localizing the antigens in the chick embryo and a method by which sera can le examined for fluorescent-stainable antibodies to Eaton's agent (3,5). Additional isolations of Eaton's agent from patients and demonstrations of fluorescent-stainable antibodies to it have been reported by Cook (6) and Chanock (7) and their associates, confirming and extending the observations of Eaton and Liu. The specificity of this fluorescent antibody reaction in terms of the etiology of the disease has been questioned (8), however, since patients with primary atypical pneumonia may develop a number of nonspecific serologic responses (9)(10)(11)(12)(13)(14)(15). Primary atypical pneumonia produced under experimental conditions in man would provide an ideal situation for comparison of these various serologic tests.…”

Cold Agglutinins. Iii. Observations on Certain Serological and Physical Features of Cold Agglutinins in Cases of Primary Atypical Pneumonia and of Hemolytic Anemia

“…The sera used in the present study were obtained from 3 types of individuals: (1) a number of patients with primary atypical pneumonia that were included in the previous study (5); (2) patients with hemolytic anemia associated with cold agglutinins but without atypical pneumonia (these cases have also been referred to in the previous studies (6)); and (3) patients and members of the hospital staff who were free of respiratory disease and of blood dyscrasia. Venous blood was drawn and cell-free serum was obtained by centrifugation after the clotted blood had been warmed at 370 C.…”

Cold Agglutinins. Vi. Agglutinins for an Indifferent Streptococcus in Primary Atypical Pneumonia and in Other Conditions and Their Relation to Cold Isohemagglutinins

“…The titers were read as the reciprocal of the highest final dilution of serum giving floccular agglutination. The method used in the cold hemagglutination tests is described in a previous paper (3).…”