Antibody-dependent cell-mediated cytotoxicity in selected autoimmune diseases.

Antibody-dependent cell-mediated cytotoxicity mediated by peripheral blood lymphocytes was studied in patients with systemic lupus erythematosus, polyarteritis nodosa. Sjogren's syndrome, and rheumatoid arthritis. The target cells were chicken erythrocytes coated with rabbit anti-chicken erythrocyte antibody. Antibody-dependent cell-mediated cytotoxic activity was normal in Sjogren's syndrome and rheumatoid arthritis but significantly decreased (P is less than 0.001) in active systemic lupus erythematosus and in two patients with polyarteritis nodosa. A partial regeneration of antibody-dependent cell-mediated cytotoxic activity was obtained by treatment with pronase and DNase followed by overnight incubation. Sera from patients with systemic lupus erythematosus inhibited antibody-dependent cell-mediated cytotoxic activity of normal lymphocytes. The inhibitory activity was studied by specific immunoadsorption and sucrose density geadient ultracentrifugation. Removal of IgG but not IgM greatly reduced inhibition. Inhibitory factors were present in 7S and heavier fractions containing IgG. Five systemic lupus erythematosus patients were studied serially to determine if improvement in clinical status could be correlated with a decrease in serum inhibitory factors as studied by inhibition of normal antibody-dependent cell-mediated cytotoxicity. Indeed, a greater serum inhibitory capacity was found in each patient during periods of greater disease activity.

Circulating immunoglobulin complexes in Wegener's granulomatosis.

Two cases of Wegener's granulomatosis are reported in which circulating immunoglobulin complexes detected during the active phase of the disease disappeared during induction of remissions of active pulmonary and renal disease by immunosuppressive agents. Elevated antiglobulin activity, urinary immunoglobulin L-chain concentration and evidence of activated coagulation mechanisms were also present during active disease, and returned toward normal with treatment. Studies showed that the serum complexes did not contain deoxyribonucleic acid (DNA) and demonstrated their immunoglobulin nature. Serum complement concentrations were normal, and no cryoglobulins were present. Immunofluorescent staining and electron microscopy of the kidney biopsy specimen of one patient showed marked fibrin deposition but no immunoglobulin or antigen-antibody deposits. Although the role of circulating immunoglobulin complexes in the pathogenesis of Wegener's granulomatosis remains uncertain, serial changes in the described parameters may provide an objective guide to activity of the disease and its response to treatment.

Efficacy of standard slow-acting antirheumatic drugs.

There are few published reports of the efficacy of slow-acting antirheumatic drugs (SAARDs) specific to the treatment of persons with early rheumatoid arthritis. Two published meta-analyses of the literature on SAARD therapy are reviewed, together with some empirical data on patients with less than 2 years' disease duration treated over an 8-year period. Although the literature suggests short-term benefit of SAARDs compared with placebo therapy, there is little to warrant considering presently available drugs to be disease-remittive agents. Based on known toxicities and purported benefits of available SAARDs, a treatment schema is proposed that responds incrementally to the course of the illness when treatment is started before irreversible joint injury occurs. The advent of new classes of therapeutic agents (eg, biologicals) for the treatment of rheumatoid arthritis warrants examination of present methods for the evaluation of antirheumatic drugs.

Lichen planus and discoid lupud erythematosus. Overlap syndrome associated with cryoglobulinemia and hypocomplementemia.

A patient with the discoid lupus erythematosus and lichen planus overlap syndrome has profound depression of serum C4 concentration associated with substantial mixed cryoblobulinemia. A family study failed to disclose evidence of a familial hypocomplementemia, cryoglobulinemia, or a dermatologic condition. Immunologlobulin, but no complement, was detected at the site of the skin abnormality. This case illustrates an immune-complex disorder with a mixed cryoglobulinemia that is related to immunoglobulin deposition in the skin.

Specificity of SLE serum antibody for single-stranded and double-stranded DNA configuration.

The solid phase immunoassay for the measurement of serum antibody to double and single-stranded DNA is described. The technique allows a more accurate definition of the antibody specificity of SLE sera as defined by inhibition techniques. The clinical usefulness of immunologic assays in the management of patients with SLE is described, including measurement of urine light chain protein concentration. A core discussion is provided to illustrate how such a panel of tests is used in management.

Utility of the fluorescent antinuclear antibody test in a single patient.

The literature on the fluorescent antinuclear antibody (FANA) test, commonly used in diagnosing systemic lupus erythematosus, was analyzed. The specificity of the test reported in early descriptive studies is much greater than the value obtained when the test is used in clinical practice. The probability of systemic lupus erythematosus in a specific patient was determined when different numbers of the classification criteria developed by the American Rheumatism Association are present. The predictive value of a positive or negative FANA test result was calculated using different pretest probabilities based on clinical criteria. The marginal benefit of the FANA test was determined as minimal at points of very large and very small pretest probability of systemic lupus erythematosus, and as maximal when five clinical criteria are present.

Practice variation in rheumatologists' encounters with their patients who have rheumatoid arthritis.

This article examines practice variation among rheumatologists in their use of time and procedures in follow-up outpatient encounters with rheumatoid arthritis patients. It focuses on differences across individual physicians rather than differences in populations of patients. In addition, the total variance is divided into parts due to patient characteristics, the providers' economic and other incentives to do procedures or reduce contact time, individual practice styles, and the random sampling of encounters. Data are taken from a stratified random sampling of U.S. rheumatologists. Analyses are based on 1,154 outpatient follow-up encounters with rheumatoid arthritis patients provided by 66 physicians, each of whom reported at least ten such encounters. There are large differences among the physicians in visit length, number of monitoring procedures used per encounter, and whether the encounter included measurements of complete blood count/urinalysis or erythrocyte sedimentation rate. Individual practice style differences are far more important causes of the variation that was observed among providers than are patient differences or practice incentive differences. It was determined that 5-40% of the cost of specific management activities could be saved by reducing the highest use.

The nature of U.S. rheumatology practice, 1977.

A description of academic and community rheumatologist practice activities in the United States has been assembled from 826 responses to a 1977 survey of American Rheumatism Association members. Reported work hours and patient load are similar to other medical subspecialists, and three-fourths of the clinical time is devoted to persons with predominantly rheumatic disease problems. Significant differences in activities occur between academic and community practices and among rheumatologists with different training backgrounds. Few characteristics vary significantly across geographic regions containing divergent rheumatologist-population ratios. Descriptive productivity measures such as these are necessary for planning; they provide part of the empirical analysis required to give reality to manpower policies.

Is health care use equivalent across social groups? A diagnosis-based study.

Previous studies of medical care utilization have controlled for medical need by signs or symptoms or broad disease classifications. The present study uses both symptoms and discrete diagnoses to control for medical need in order to determine if the use of ambulatory and hospital care differs by race, income, education, insurance coverage, or region. Using data from the 1976 National Health Interview Survey, we found that there were no consistent differences in the number of physician visits made in a year by these characteristics, medical need held constant. Lack of insurance coverage was associated with fewer hospitalizations in a year for five of nine chronic diseases under review. Race was associated with fewer hospitalizations for two conditions prevalent among minorities. These effects were not evident when medical need was controlled solely by signs or symptoms.