Decreased 19S antibody response to bacterial antigens in systemic lupus erythematosus

The immunogenicity and potential for disease modification of pneumococcal polysaccharide vaccine in systemic lupus erythematosus were evaluated in a controlled, double-blind study. Forty patients were randomly chosen to receive an intramuscular injection of either vaccine or placebo. Changes in mean antibody concentrations (nanograms antibody nitrogen per milliliter serum) to 12 type-specific pneumococcal capsular antigens from prevaccination to one month after vaccination were 177 to 1045 in the vaccine (P < 0.001) and 164 to 153 in the placebo-treated patients. In the month after vaccination, neither vaccine nor placebo-treated patients had a significant change in lupus disease activity as assessed by a composite clinical, laboratory, and serologic index. We conclude that patients with systemic lupus erythematosus can be successfully immunized with pneumococcal vaccine without detectable alterations of the underlying disease. Infections are a major cause of morbidity and mortality in patients with systemic lupus erythematosus (1-6). The potential protection afforded by immunuations might be of benefit in this infection prone population provided that vaccines are immunogenic and do not result in disease exacerbation. Recent studies have demonstrated that patients with systemic lupus can be successfully immunized to influenza without any apparent effects on the underlying disease (7-11). Recognition that immunization of patients with systemic lupus can be both effective and safe leads to consideration of other immunizations.We report here an evaluation of the immunogenicity and clinical and serologic effects of a pneumococcal polysaccharide vaccine in systemic lupus erythematosus in a controlled, randomized study. MATERIALS AND METHODSThe study population consisted of 40 patients with systemic lupus erythematosus who satisfied preliminary classification criteria (12). The average patient age was 32 years (range 14-61), and 39 were females. Patients with surgical splenectomies were excluded from the study. Most of the patients had a relatively stable disease course and were followed during the period of study in the outpatient clinic. Drugs being taken at the time of study participation included varying doses of corticosteroids in 31 patients, nonsteroidal antiinflammatory drugs in 20 patients, and antimalarials, either chloroquine or hydroxychloroquine, in 17 patients. Five of the patients studied were receiving no medications; none was receiving cytotoxic drugs.

Section: Discussionsupporting

confidence: 84%

A controlled study of pneumococcal polysaccharide vaccine in systemic lupus erythematosus

Klippel

Karsh

Stahl

et al. 1979

“…Decreased in helper function might result in a decrease in primary recognition. This might lead to a decrease in the 19s response to new antigens as described by Baum and Ziff (37) for Brucella several years ago, and play a role in the increased incidence of infection. Bach and Bach (38) have recently demonstrated that recognition and killing may also be separate functions shared between T-cells in cell mediated immunity.…”

Section: T-and B-lymphocytes In Ramentioning

confidence: 98%

Clinical aspects of T‐ and B‐lymphocytes in rheumatic diseases

Messner¹

1974

The recent increase in basic knowledge of thymic dependent (T-cell) and bone marrow dependent (B-cell) lymphocyte cooperation in the normal immune response has provided new and challenging concepts to apply to the study of rheumatic diseases. An excellent example of this approach is the theory proposed by Allison and his colleagues (1) suggesting how T and B lymphocytes might interact to produce autoantibodies.They postulate that in the normal response to thymus dependent foreign aiiti- gens a T-cell with anticarrier specificity recognizes the carrier portion of the antigen, and then cooperates with a B-cell which recognizes the hapten portion and produces antibody to the hapten. They also suggest that all normal individuals possess B-cells capable of recognizing self constituents and producing autoantibody; but that autoantibody is not made because T-cells do not recognize, or are tolerant, to self antigens. In this scheme, tolerance could be broken in several ways.For example, a virus attached to a self component, such as a cell, might be recognized by a T-cell specific for the virus. This T-cell could cooperate with a B-cell capable of recognizing self antigens on the cell surface. With the aid of this cooperation the B-cell could then produce antibody against the cell. In the case of an antigen attached to a self component, possibly an antigen attached to an antibody, the antigen might be recognized by a T-cell. This T-cell could then act as a helper cell for a B-cell which could recognize the carrier antibody. This B-cell could then make antibody to the antibody which we would

“…Moreover, immunization of SLE patients (35,36) or immunization of mice (37)(38)(39) with protein antigens fails to induce an abnormal response to the immunogen or to augment autoreactivity. Lupus patients actually produced a lower antibody response to influenza (35) and Brucella (40) vaccines and were shown to have lower agglutinating titers to E coli and Shigella, as compared with normal controls (40). The variable increases in virus antibody titers reported for patients with SLE (41-43) may be explained by autoantibody reactivity with intracellular autoantigens, since most of the assays were performed with crude extracts of virus-infected mammalian cells.…”

Section: Discussionmentioning

confidence: 99%

Untitled

1988

Antibody binding to total protein extracted from a mammalian source (HeLa cells) and from a prokaryotic source (Escherichiu coli) was compared in sera from patients with systemic lupus erythematosus (SLE) and sera from normal subjects. When the average numbers of peptides or proteins recognized by IgG antibodies were compared on immunoblots, SLE sera bound to a significantly greater number of proteins from the HeLa cell extract than did sera from normal individuals (P < 0.001). In contrast, SLE sera actually bound to fewer E coli proteins than did the sera obtained from normal controls, although the difference was not statistically significant. There was no correlation between the number of E coli proteins and HeLa proteins recognized by individual SLE sera, and there was no trend toward reactivity with a larger number of antigens in sera containing higher levels of IgG. IgG from SLE sera did not bind to 6 purified eukaryotic protein standards (selected solely on the basis of differences in size and charge) either in their denatured state or in their native state. These findings indicate that the high levels of IgG antibodies against selected eukaryotic intracellular pro- May 23, 1988. teins in patients with SLE cannot be explained by a random polyclonal B cell activation.The etiology of autoantibody production in systemic lupus erythematosus (SLE) is uncertain. Some investigators have attempted to explain autoantibody production by intrinsic B cell hyperactivity (for review, see ref. 1) or by T lymphocyte suppressor cell deficiency (2,3). Such mechanisms would be expected to result in a broad (polyclonal) B cell expansion (4), with a presumably random profile of abnormal antibody reactivity. Recent analyses of autoantibody specificities in SLE, however, suggest that of the approximately 2,000 mammalian intracellular proteins detectable by current methods (3, only relatively few are targeted by lupus autoantibodies (6).To further determine whether sera from patients with SLE are broadly reactive to the universe of potential antigens, we compared the antibody reactivity of lupus sera with that of sera from normal individuals. Purified eukaryotic protein standards and total Escherichia coli cell extracts were used as antigen sources. Our findings indicate that lupus sera do not show increased or unusual binding to randomly selected eukaryotic proteins nor to the many hundreds or thousands of potential E coli protein epitopes (7) displayed on an immunoblot .