Depression of cellular‐mediated immunity in systemic lupus erythematosus

The contribution of immune regulation to the etiology of systemic lupus erythematosus (SLE) is poorly understood. Using the monoclonal antibodies OKT4 and OKTS, we quantitated, by flow cytometry, T inducer/ helper and T cytotoxicfsuppressor cells in patients with SLE. Serologically active patients, who had clinical manifestations such as arthritis or rash and were not receiving prednisone, were characteristically lymphopenic due to a marked reduction in OKT4+ cells. Prednisone therapy produced the same phenomenon. Untreated patients, who were serologically inactive, demonstrated no abnormalities. These studies have thus revealed two presumably independent factors that can produce similar immunoregulatory aberrations.Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by excessive immunoglobulin and autoantibody production. Although B cell function is increased, T cell functions which include delayed hypersensitivity (1-3, mitogenic reactivity (6,7), generation of antigen-specific reactivities (8), and development of nonspecific suppressor (14).We studied 28 patients with SLE who were divided into groups based on corticosteroid therapy and serologic evidence of disease activity. We will describe clinically significant abnormalities in the absolute number and relative proportions of immunoregulatory T cell subsets based upon this classification. PATIENTS AND METHODSPatients. This study included 28 patients (24 females, 4 males) with SLE according to the American Rheumatism Association ( M A ) preliminary criteria (15). Two to 3 patients were randomly selected in the lupus clinic visits each month from April 1981 to April 1982. These patients were then separated into 2 groups based on existing therapy, one receiving more than 10 mg prednisone per day, the other receiving 10 mg or less of prednisone per day. A special attempt was made to isolate newly diagnosed lupus patients being treated with 10 mg or less prednisone per day. During this 1-year period, 11 newly diagnosed patients were seen, but only 6 had 4 or more ARA preliminary criteria; of these 6, only 5 were treated with less than 10 mg prednisone per day.Control groups consisted of 16 women and 5 men with scleroderma and 16 patients with lepromatous leprosy. They will be described in detail elsewhere. Normal individ-

Section: Discussionmentioning

confidence: 99%

T Lymphocyte Subsets in Systemic Lupus Erythematosus

Bakke

Kirkland

Kitridou

et al. 1983

“…Our study population was a clinically stable population which was chosen to eliminate, as much as possible, the known influences of changes of disease activity and medication on immunologic function (35,36). There were no apparent differences in these factors between the normoresponsive and hyporesponsive patients.…”

Section: Discussionmentioning

confidence: 99%

Anti‐tetanus toxoid antibody synthesis after booster immunization in systemic lupus erythematosus

Nies¹,

Boyer²,

Stevens³

et al. 1980

The in vivo and in vitro synthesis of anti-tetanus toxoid antibody (anti-tet) was measured after booster immunization with tetanus toxoid in 9 patients with systemic lupus erythematosus (SLE) and 9 controls. In vitro culture of peripheral blood lymphocytes (PBL) from both patients and controls showed maximal antitet synthesis 7 days after booster immunization, and maximal serum titers occurred by day 14. The initial in vitro burst of anti-tet synthesis was not dependent upon pokeweed mitogen (PWM) stimulation, whereas later synthesis was PWM dependent. Two differences between patients and controls were observed: 1) patients with SLE had a lower mean pre-boost serum titer of anti-tet, and 2) one-third of the patients showed a blunted serum anti-tet response. To study whether these abnormalities were a result of altered immune regulation, anti-tet synthesis was measured by the coculture of separated SLE-B or control-B cells and separated SLE-T or control-T cell populations (+ irradiation to remove suppressor T cell activity). These coculture studies showed that both abnormalities were due to a lack of SLE-B cell response, not to abnormalities of SLE-helper T or SLE-suppressor T cell function.

“…Studies have demonstrated a substantially increased prevalence of certain of these serologic abnormalities in relatives of SLE patients, a finding suggesting that genetic factors are important in their production (5). Impaired cell-mediated immunity in SLE (6) has been related either to intrinsic cellular deficiencies (7) or to inhibiting serum factors, particularly antilymphocyte antibodies (8), or to both (9-1 1). It also has been postulated that a deficiency of "suppressor" T cells may result in heightened humoral responses (1 2).…”

Section: Genetic Immune and Viral Factors Have Been Implicated In Tmentioning

confidence: 99%

Immunologic observations on 9 sets of twins either concordant or discordant for SLE

Block

Lockshin

Winfield

et al. 1976

The influence of genetic and nongenetic factors on abnormalities of the immune response in systemic lupus erythematosus (SLE) was studied in 9 sets of twins in which one or both twins had SLE. Particular emphasis was placed on contrasting the results between the sibs of 3 monozygotic pairs discordant for clinical SLE. Depression of cell-mediated immunity, determined by lymphocyte blastogenic response to mitogens, was associated with the clinical expression of illness. In contrast, autoreactive antilymphocyte antibodies and lymphocyte tubu- loreticular structures were found in both clinically affected and unaffected subjects and were more prominently associated with the presence of other serologic abnormalities. No evidence of antigens or cell surface determinants unique to affected sibs was encountered. Genetic, immune, and viral factors have been implicated in the pathogenesis of systemic lupus erythematosus (SLE).A genetic influence has been suggested by studies demonstrating an increased prevalence of SLE in first degree relatives of SLE patients and multiple occurrences of SLE within single faGilies (1,2). Extremely high concordances of clinical SLE and serologic abnormalities between monozygotic twins have recently been reported (3). Evidence for abnormal immune function in SLE is well known, including "autoantibodies," which have been related to tissue injury (4). Studies have demonstrated a substantially increased prevalence of certain of these serologic abnormalities in relatives of SLE patients, a finding suggesting that genetic factors are important in their production (5). Impaired cell-mediated immunity in SLE (6) has been related either to intrinsic cellular deficiencies (7) or to inhibiting serum factors, particularly antilymphocyte antibodies (8), or to both (9-1 1). It also has been postulated that a deficiency of "suppressor" T cells may result in heightened humoral responses (1 2).In the SLE-like and leukemic illnesses of New Zealand mice, in which the presence of genetic and