Immunopathologic studies of pneumonitis in systemic lupus erythematosus.

We performed immunohistopathologic studies on biopsied lung tissue obtained from two patients with lupus pneumonitis using immunofluorescence, immunoperoxidase, electron microscopy, and acid-microelution. In both patients, immunofluorescence showed granular deposits of IgG, the third component of complement (C3), and DNA in the alveolar walls. The immunoperoxidase technique in both and electron microscopy in one showed that these deposits were in the interstitium of the alveolar walls and in the alveolar capillary walls. The eluates obtained from cryostat sections of the biopsied lungs contained antinuclear factor of IgG class in one patient and showed anti-DNA antibody activity in both. We suggest that the deposits are immune complexes composed of DNA, anti-DNA antibody, and complement and that deposits of DNA-anti-DNA immune complex may play a role in lupus pneumonitis.     

Clinical immunologic studies in systemic lupus erythematosus

This review of recent and new directions in clinical immunologic studies of systemic lupus erythematosus (SLE) is restricted to the areas of lymphocyte surface markers, antigen binding lymphocytes, immune complexes, and lymphocyte hyporesponsiveness in lupus patients. First, it is not clear whether the T-lymphopenia observed in SLE is related to viral destruction of T cells, anti-lymphocyte antibodies, or tissue sequestration. Second, the increase in DNA-binding B lymphocytes observed in active lupus patients may be related to minor alterations in the balance of immunoregulatory T cells or to a bypass of DNA-specific helper T cells. Third, it is speculated that the removal of immune complexes which play a role in lupus glomerulitis by various extracorporeal immune absorbents may be important in the future therapy of SLE. Fourth, the mechanisms of T-lymphocyte hypofunction are unexplained. It is postulated from studies done in other diseases that this hypoactivity may be mediated by the secretion of prostaglandin or other humoral agents from one leukocyte subpopulation suppressing another potentially responsive lymphocyte subpopulation. Also an investigation into the lymphocyte subpopulation reactive with virus-infected fibroblasts may be useful in delineating immunoregulatory lymphocytes important in the pathogenesis of SLE.     

Toxoplasmosis and systemic lupus erythematosus. Comparative serological studies.

There are still controversial views as to the relation between SLE and toxoplasmosis. Therefore, we looked for serological markers in both diseases. In patients with SLE (17), toxoplasmosis (28), and in normal controls (28) anti-Toxoplasma gondii antibodies, anti-nuclear antibodies of different specificities, anti-histone and anti-cardiolipine antibodies, as well as antibodies against most common public idiotypes were measured. Significant increases in antinuclear antibodies and other SLE-related antigens were observed in patients with SLE. On the contrary, low levels of these antibodies were found in toxoplasmosis patients and in controls. The same was true for 16/6 anti-DNA idiotype antibodies. The incidence of anti-Toxoplasma antibodies in SLE sera did not differ in comparison with that in the normal population. Our data suggest that subacute and chronic toxoplasmosis do not play essential roles in generating the antibodies that are important to the pathogenetic mechanism operating in SLE.     

Type C oncornavirus studies in systemic lupus erythematosus

The following paper critically reviews published evidence that concerns the occurrence of viruses in patients with systemic lupus erythematosus. Special emphasis is placed on the recent studies that implicate type C oncornaviruses. Evidence from our laboratory regarding the occurrence of type C viruses in these patients is predominately negative. It is concluded that the pathogenesis of systemic lupus erythematosus is almost certainly multifactorial and that the part that viruses play remains hypothetical.     

Immunological studies on bronchial secretion. II. Antibodies against bronchial secretion in systemic lupus erythematosus and asthmatic patients.

Bronchial secretion was tested by double gel-diffusion with sera from 100 asthmatic patients, 72 systemic lupus erythematosus patients, 29 patients with other diseases and 31 normal individuals. Positive gel-diffusion reactions were observed only in the sera from two patients with S.L.E. Sera from 100 asthmatic patients, 29 non-allergic patients and 31 normal individuals, tested with bronchial secretion by the passive haemagglutination and inhibition test, showed only three positive reactions with sera from asthmatic patients. Two problems were discussed: the immunological relationship between antigenic determinants found in the sputum and serum in S.L.E. patients; and the possibility that the bronchial secretion being reabsorbed might act as an auto-antigen.     

Serologic studies of monozygotic twins with systemic lupus erythematosus.

OBJECTIVE. The goal of these studies was to assess the role of genetic factors and disease expression in the pattern and titer of autoantibodies to several RNA protein antigens in patients with systemic lupus erythematosus (SLE) by studying identical twins concordant and discordant for disease expression. METHODS. Autoantibodies to Ro/SS-A, La/SS-B, U1 RNP, and Sm were measured by quantitative enzyme-linked immunosorbent assay using affinity-purified antigens. RESULTS. Detailed serologic studies were performed in 7 pairs of identical twins, 3 of whom were concordant and 4 of whom were discordant for disease expression. Autoantibody titers were higher in affected than in unaffected twins from discordant pairs, but in 3 of 4 pairs, the profile of anti-RNA proteins (e.g., Ro/SS-A, La/SS-B, U1 RNP, and Sm) was virtually identical. In the SLE pairs concordant for disease expression, the autoantibody titers were very similar, as were the anti-RNA protein profiles. When the identical twins were matched by sex, race, and age to pairs of nontwin SLE patients, the 6 white twins shared an average of 2.5 (+/- 1.05 SD) anti-RNA proteins, while the control SLE pairs shared only 0.33 (+/- 0.82), P less than 0.01 (t = 4.0, P less than 0.01). In addition, in the white SLE twins, all had elevated levels of anti-U1 RNP while in white nontwin SLE patients, the frequency of anti-U1 RNP was 30%. CONCLUSION. These data point to a dominant role for genetic factors in the determination of specific autoantibody profiles.     

ANA-negative systemic lupus erythematosus.

The presence of antinuclear antibodies (ANA) in serum is generally considered a decisive diagnostic sign of systemic lupus erythematosus (SLE). Ten patients with clinical signs of disease but persistent negative tests for ANA are examined in this study. Hair fall, Raynaud's phenomenon and recurrent oral ulcers were common in the ANA-negative group. ANA-negative SLE seems to be a subgroup of SLE that has not previously been given adequate attention.     

Fever in systemic lupus erythematosus.

The frequency, causes, clinical and laboratory features, and outcome of febrile episodes in 160 hospitalized patients with systemic lupus erythematosus were reviewed. Eighty-three febrile episodes were identified in 63 patients and were ascribed to active lupus erythematosus alone (60 per cent), infections (23 per cent) and miscellaneous causes (17 per cent). Bacteremia was present in nine of the 19 infectious episodes and resulted in a fatal outcome in a third of the patients. Leukocytosis, neutrophilia, shaking chills and normal levels of anti-DNA antibodies were associated with infection in febrile patients with lupus erythematosus.     

Ascites in systemic lupus erythematosus.

Peritoneal serositis is not a widely recognised aspect of systemic lupus erythematosus (SLE). Indeed, ascites in SLE is said to occur only when complicated by the nephrotic syndrome, congestive cardiac failure, or hepatic cirrhosis. We describe two patients who developed ascites that could be attributed to none of these complications.     

Sequential studies of complement activation in systemic lupus erythematosus

C1 and C3 activation, measured as C1r-C1s-C1 inactivator C1s-C1r-C1IA complexes in serum and circulating C3d were studied in serial samples from 33 patients with SLE. All patients demonstrated exacerbations during observation periods of 10-30 months and were divided into groups according to principal clincal features (mild SLE, severe extra-renal SLE, and lupus glomerulonephritis). Increased C1 activation was consistently found during exacerbation. C3d in plasma was a feature associated with severe disease flares. Activation of C1, but not of C3, was documented before flare-ups of disease activity, but such predictive information was mostly restricted to patients with extra-renal disease. C2 cleavage in plasma, studied serially in a few patients, appeared to be closely associated with C1 activation. Circulating immune complexes, measured with solid-phase C1q assay, did not always increase before development of clinical manifestations. Remission of symptoms was paralleled by decreasing concentrations of C1r-C1s-C1IA and of, when present, C3d. Similar findings were made for immune complexes but only in severe disease. Persisting C3d was observed in 3 patients, who subsequently developed renal failure. C1q levels were transiently low during flare-ups of lupus glomerulonephritis, but otherwise the concentrations of C1q, C4 and C3 did not show consistent patterns of variation in relation to disease activity.     

Genetics of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which multiple genes appear to play important roles in pathogenesis. Hereditary deficiencies, both complete and partial, of several components of the complement system clearly predispose to lupus. HLA class II alleles appear to mediate specific autoantibodies, many of which are pathogenic. Modern molecular techniques are now providing insight into the specific major histocompatibility complex class II polymorphisms that are associated with different autoantibodies in SLE. Other genetic systems also may be important.     

Treatment of systemic lupus erythematosus.

Reports on a variety of therapies for systemic lupus erythematosus have been published over the past year. Most of these are single case reports or open studies. As reported last year in this journal, the potential uses of intravenous gamma globulin and plasmapheresis continue to be explored. The use of cyclophosphamide for nonrenal manifestations follows studies last year of its use for lupus nephritis. No major double-blind studies of therapy for lupus nephritis were published; however, the course of lupus patients receiving dialysis or grafts was the subject of three interesting studies. An interesting study on the ability of hydroxychloroquine to prevent disease exacerbations was also published. In summary, the reports of therapy over the past year represent variations on themes. The use of new agents will most likely be based on improvements in our understanding of the pathogenesis of systemic lupus erythematosus.