Frederic C. McDuffie

Immune complexes in sera and synovial fluids of patients with rheumatoid arthritis. Radioimmunoassay with monocylonal rheumatoid factor.

Evidence for the presence of immune complexes in blood, synovial fluid, and tisues of patients with rheumatoid arthritis (RA) includes low complement levels in blood and effusions, deposition of immunoreactants in tissues and vessel walls, precipitate formation after addition of monoclonal rheumatoid factor (mRF) to serum or synovial fluid. To quantitate immune complex-like material in RA patients, we developed a radioimmunoassay based on inhibition by test samples of the interaction of (125I)aggregated IgG (agg IgG) and mRF coupled to cellulose. This method could measure immune complexes of human antibody with hemocyanine prepared in vitro. The assay was not influenced by presence of polyclonal RF in test samples, nor by freezing and thawing. Normal levels of immune complex-like material in serum were less than 25 mug agg IgG EQ/ML. 12 of 51 RA sera examined (26%) contained more than 25 mug/ml. The presence of this material in RA sera was found to correlate with severity of disease, as measured by anatomical stage and functional class. There was an inverse correlation of the material with serum C4 level. Rheumatoid synovial fluids generally contained higher levels than serum, and five of 23 contained very much higher levels. The frequency of elevated levels of immune complex-like material in sera of patients with systemic lupus erythematosus (2 of 29) and with miscellaneous vasculitides (2 of 21 was much lower than in RA, suggesting that mRF exhibits a specificity for only certain kinds of immune complexes. The reason for this apparent specificity may explain such distinctive features of RA as the high frequency of polyclonal RF, the lack of immune complex nephritis, and the generally normal levels of serum complement.

Treatment of Lupus Nephritis with Prednisone and Combined Prednisone and Azathioprine

Abstract The relative effectiveness of high-dose prednisone (group A) was compared with the same regimen plus azathioprine (group B) for the treatment of lupus nephritis of mild or moderate severit...

Pleural Fluid Complement in Systemic Lupus Erythematosus and Rheumatoid Arthritis

Abstract Whole hemolytic complement and three components (C1q, C4, and C3) were measured in pleural fluids obtained from 50 patients—23 with malignant disease, 6 with lupus erythematosus, 6 with rh...

Serum and Blister Fluid Anticomplementary Activity in Pemphigus and Bullous Pemphigoid. Sucrose Density Gradient Studies

Summary By sucrose density gradient ul-tracentrifugation and standard hemolytic complement assays, complement fixing activity of about 19 S and greater was found in blister fluids of one patient with pemphigus and three of five patients with bullous pem-phigoid. Control blister fluids, including experimentally induced blisters, lacked such activity. Complement fixing activity was apparent, however, in 6 of 10 pemphigus sera and in two of five bullous pemphigoid sera tested. The material present in both pemphigus and bullous pemphigoid appears to activate the classical complement pathway.

Prothrombin, thrombin and prothrombin fragments in plasma of normal individuals and of patients with laboratory evidence of disseminated intravascular coagulation

Abstract With specific immunoassays for prothrombin, thrombin-anti-thrombin-III complex and for prethrombin-1 antigen, we measured the levels of these proteins in the plasma of normal individuals and patients suspected of having chronic disseminated intravascular coagulation (DIC). The normal level of prothrombin in plasma was found to be 110–212 mg/liter, and of thrombin-anti-thrombin-III complex and prethrombin-1 antigen approximately 1 μg/ml. In patients with suspected DIC, prothrombin levels, as measured by immunoassay and two-stage clotting assay, were decreased in 14 of 19 studied. Levels of thrombin-anti-thrombin-III complex were normal in all the patients and those of prethrombin-1 elevated in only two of 19. The lack of elevation of these products is probably due to the small amount of prothrombin activated in these patients. Decreased synthesis may account for the low levels of prothrombin observed in some. Measurement of the level of these products of prothrombin is therefore not useful in the diagnosis and management of patients with DIC.

Immune complexes in the rheumatic diseases

The serum sickness model of immune complex disease developed by Germuth’ and Dixon and associate? some 2.5 years ago remains the prototype for the study of human diseases in which immune complexes are suspected of playing a role. Fig. 1 shows some of the most important criteria for implicating immune complexes in the pathogenesis of inflammatory lesions. An increase in the rate of clearance of intravenously administered ‘311-labeled antigen at day 10, a fall in the level of serum complement, the appearance of antigen complexed to antibody in the blood, and, in addition, the presence of antigen, antibody, and complement components in the lesions demonstrable by fluorescein-labeled antibodies provide convincing evidence for this cause-and-effect relationship. Although systemic lupus erythematosus (SLE) is a relatively rare disease (prevalence, 14 to 48 per 100,000 population),” nonetheless, because of the large number of immunologic abnormalities associated with it, it has become the subject of intense investigation over the past 20 years. Low serum complement levels have been recognized as characteristic of this disease since 195 1’ and a clear relationship with the presence and severity of renal disease has been documented.” Deposits of immunoglobulins and complement components in a location between the endothelial cell layer and the basement membrane in a lumpy, bumpy pattern mimicking that of experimental serum sickness is characteristic of lupus nephritis.6 Immune complex-like material has been detected in the plasma of lupus patients by a number of techniques, most of which depend on binding of IgG aggregates to Clq7 or to receptors for IgG and complement components on cells.x For some as yet unexplained reason these aggregates in lupus sera cannot be detected with monoclonal rheumatoid factors

Synovial Fluid Complement: Usefulness in Diagnosis and Classification of Rheumatoid Arthritis

Abstract The relation between synovial fluid complement concentration and severity or prognosis of disease was studied in 62 patients with rheumatoid arthritis who were divided into 4 groups, on th...

CLINICAL AND PSYCHOLOGICAL PATTERNS IN AUTO-ERYTHROCYTE SENSITIVITY.

Excerpt Auto-erythrocyte sensitivity is a syndrome characterized by painful reddish lesions on the skin that come on very abruptly, and they rapidly become ecchymotic in character. Originally descr...

Role of Lupus Erythematosus Factor and Accessory Serum Factors in Production of Extracellular Nuclear Material

Excerpt Since the original description of the lupus erythematosus (LE) cell by Hargraves, Richmond, and Morton (1), it has become clear that this inclusion-containing cell is formed in two stages (...

Twenty Years of the Lupus Erythematosus Cell

Excerpt In November 1968 a symposium was held in Rochester, Minn., to commemorate the twentieth anniversary of the discovery of the lupus erythematosus (LE) cell by Hargraves, Richmond, and Morton ...