IMMUNOLOGIC STUDIES OF HEART TISSUE : III. OCCURRENCE OF BOUND GAMMA GLOBULIN IN AURICULAR APPENDAGES FROM RHEUMATIC HEARTS. RELATIONSHIP TO CERTAIN HISTOPATHOLOGIC FEATURES OF RHEUMATIC HEART DISEASE

Using fluorescent antibody methods, deposits of bound gamma globulin, as determined in unfixed washed sections of auricular appendages from rheumatic hearts, were noted in a significant number (18 per cent) of 100 specimens studied. Such deposits were observed in myofibers, sarcolemma, interstitial connective tissue, and vessel walls. Albumin and fibrin were generally found absent from these sites. Control hearts from normal and pathologic material, including postmortem and biopsied specimens, in general, did not reveal such deposits. These various tissue sites which contained bound gamma globulin frequently exhibited evidence of alteration as indicated both by enhanced affinity for eosin and by strongly positive reaction with the periodic acid-Schiff reagent, and appeared comparable in some cases to "fibrinoid." Bound gamma globulin was not observed in cellular or stromal components of Aschoff lesions, nor was the occurrence of Aschoff lesions correlated with presence of bound gamma globulin. It is suggested that deposition of gamma globulin and the eosinophilic alteration associated with such deposition are related to certain of the pathologic changes of rheumatic heart disease. The nature of such deposits of gamma globulin was considered from immune and non-immune points of view.     

STUDIES IN THE RELATION OF THE HEMOLYTIC STREPTOCOCCUS TO RHEUMATIC FEVER : III. COMPLEMENT FIXATION VERSUS STREPTOCOCCAL NUCLEOPROTEINS WITH THE SERA OF PATIENTS WITH RHEUMATIC FEVER AND OTHERS

Complement-fixing antibodies to the cytoplasmic particles (CP) and to the S fraction of streptococcal nucleoproteins are present in normal human sera, the range of concentrations varying among the age groups. The titer of these antibodies rises between the first half-week and the 3rd week of scarlet fever, in more than 80 per cent of the cases. The titers then remain elevated for at least 4 months. In children, 91 per cent of the normal sera examined showed anti-CP titers up to 32; 87 per cent of sera in active rheumatic disease had titers above this level. Corresponding data with S fell in the same range of percentage distribution. Anti-CP and anti-S titers remained elevated long after the rheumatic process had reached quiescence. No correlation of serologic titer with the degree of clinical activity was found in the case of either antibody.     

抗ENA4种试剂盒对风湿病诊断性能的比较研究

临床上与自身免疫有关的一组疾患，如红斑性狼疮（SLE），类风湿性关节炎（IRA），多发性肌炎（PM），皮肌炎（SM），多发性系统性硬化（SS），Sjogren综合症（SjS）等曾命名为结缔组织病，现统一归类为风湿病。     

EXPERIMENTAL NEPHRITIS IN RATS INDUCED BY INJECTION OF ANTI-KIDNEY SERUM : III. PATHOLOGICAL STUDIES OF THE ACUTE AND CHRONIC DISEASE

Administration of the relatively organ specific antibody, so called nephrotoxin, present in anti-kidney serum, is followed by a diffuse glomerulonephritis. This is characterized early by swelling of the intercapillary substance of the glomerular tuft and by tubular degeneration. Fibrin thrombi are only present in the glomerular capillaries when the injection of anti-kidney serum results in a severe anaphylactoid reaction, and are due to factors other than nephrotoxin. The urinary abnormalities which develop in all rats after a suitable injection of nephrotoxin usually continue until the animal dies or is sacrificed. Microscopic renal lesions of the early phase merge into scarring of the glomeruli and tubules. Histological study of those animals which die from 3 to 11 months after treatment reveals a chronic progressive glomerulonephritis with generalized vascular lesions.     

IMMUNOLOGIC RELATION OF STREPTOCOCCAL AND TISSUE ANTIGENS : III. PRESENCE IN HUMAN SERA OF STREPTOCOCCAL ANTIBODY CROSS-REACTIVE WITH HEART TISSUE. ASSOCIATION WITH STREPTOCOCCAL INFECTION, RHEUMATIC FEVER, AND GLOMERULONEPHRITIS

Sera from patients with recent streptococcal infection or non-suppurative sequelae exhibit with variable frequency a precipitin reaction in agar gel with a partially purified streptococcal antigen which has been shown previously to be immunologically related to human heart tissue. This precipitin could be absorbed from sera with normal human heart tissue homogenates but not with homogenates of other organs. Demonstration of this cross-reaction by heart absorption was found dependent both upon the serologic properties of individual sera and the nature or state of purification of the streptococcal product employed as test antigen. Evidence was obtained of a close association of heart-related and non-heart-related antigenic determinants in partially purified preparations of the streptococcal antigen by both gel diffusion and immunoelectrophoresis. On immunoelectrophoretic analysis, cross-reactive antigen exhibited a more rapid mobility toward the anode than M protein. It was destroyed by digestion with trypsin, pepsin, and chymotrypsin. Based on specific absorption tests with a Type 5 and Type 19 strain, the antigen was localized to cell walls and to a lesser extent to cell membranes of these strains. Precipitating activity related to cross-reactive antibody was localized to the immunoglobulin zone in immunoelectrophoresis. Reactive sera showed diminution or loss of serological activity following heat inactivation at 56°C or after prolonged storage at 4°C. Sera containing cross-reactive precipitating antibody exhibited an immunofluorescent reaction with sarcolemma of cardiac myofibers, which was inhibited by streptococcal cross-reactive antigen. By this inhibition test, the immunofluorescent reaction related to cross-reactive antibody could be distinguished from that due to other heart-reactive factors. Antibody to streptococcal cross-reactive antigen defined by precipitation-absorption tests was observed in 24 per cent of patients with recent history of uncomplicated streptococcal infection and in the majority of patients with acute rheumatic fever, rheumatic heart disease, or acute glomerulonephritis. It was observed rarely in patients with non-streptococcal related disease. These data provide evidence that induction of cross-reactive autoantibody to heart in certain individuals is associated with streptococcal infection.     

STUDIES ON THE RELATIONSHIP OF STREPTOCOCCUS HEMOLYTICUS TO THE RHEUMATIC PROCESS : II. OBSERVATIONS ON THE BIOLOGICAL CHARACTER OF STREPTOCOCCUS HEMOLYTICUS ASSOCIATED WITH RHEUMATIC DISEASE

To determine the nature of the organisms associated with outbreaks of rheumatism at The Pelham Home, in a large number of individuals at the Presbyterian Hospital Nurses'' Training School and among rheumatic subjects in New York City under continuous clinical observation, studies of the throat flora have been conducted. Hemolytic streptococcus in most instances appeared in the pharynx from 1 to 5 weeks before the onset of the rheumatic attack. These organisms have been investigated with the usual types of bacteriological tests and, in addition, have been classified serologically according to Lancefield''s technique. The results have demonstrated that the organisms were not of a single type, but fell into six antigenic groups. The majority of the freshly isolated strains tested were strong toxin producers. The organisms producing the strongest toxin were cultures from the patients who developed extremely intense rheumatism. About 70 per cent of these toxins were neutralized by a monovalent streptococcus antiserum.     

PERSISTENCE OF STREPTOCOCCAL GROUP A ANTIBODY IN PATIENTS WITH RHEUMATIC VALVULAR DISEASE

Antibody levels to streptococcal Group A and A-variant carbohydrates were determined using a radioactive immune precipitation technique on patients with rheumatic fever, with and without valvular disease, on patients with post-streptococcal acute glomerulonephritis, and on age-matched controls. During the acute phase of the above illness, the means of the antibody levels to both carbohydrate antigens were equally elevated and were significantly higher than the normal controls. When Group A antibody levels were determined on sera obtained at intervals of 5–12 months and 1–5 yr after the acute illness) it was found that the antibody levels declined within the normal range at the 5–12 month interval in patients with glomerulonephritis as well as in patients with rheumatic fever in whom no valvular involvement had complicated the disease, i.e., patients with pure Sydenham's chorea. However, in patients with rheumatic valvulitis, who had been on penicillin prophylaxis after the last acute episode, the A antibody level showed little decline from the level obtained during the acute illness. The elevated antibody level in patients with rheumatic valvulitis, including patients with Sydenham's chorea with valvulitis, persisted for periods of at least 1 yr and up to 20 yr after the last acute attack. The pattern of the decline of the antibody levels to the A-variant carbohydrate as well as of the antibody titers to the other streptococcal antigens tested, ASO and anti-DNase B, was similar in all patients studied regardless of the presence of valvular disease. These findings suggest that prolonged persistence of the Group A antibody is a phenomenon peculiar to patients with rheumatic valvular disease. Whether this persistence is involved in the pathogenesis or is an outcome of the valvular disease remains to be determined.