Immune complexes in progressive systemic sclerosis (scleroderma)

Abstract

Serum immune complexes were measured in 92 patients with progressive systemic sclerosis, and elevated levels were found as follows: Raji cell assay 72% (59% after pronase treatment of Raji cells), agarose gel electrophoresis 52%, and Clq binding 24%. Fortythree (47%) had abnormal results on two or more of these tests, but only 17 (18%) had normal results by all three assays. Computer-assisted analysis of immune complex results and extensive clinical and laboratory data compiled on these patients revealed that the patients with abnormal Raji cell assays more often had diffuse scleroderma, tendon friction rubs, and positive serum antinuclear antibody tests than did patients with negative results on Raji cell assays. Individuals with immune complexes detected by Clq binding had evi- dence of pulmonary involvement and positive serum rheumatoid factor more frequently than did patients whose Clq tests were negative.The etiology of progressive systemic sclerosis (PSS, scleroderma) is unknown. Any hypothesis concerning the pathogenesis of this disease must account for both the prominence of vascular lesions in involved tissues (1,2) and the high frequency of abnormal serologic and cellular immune reactions (3). Initiation or mediation of vascular damage by circulating immune complexes might satisfy these requirements. In reports to date on immune complexes in PSS, investigators have studied small groups of patients and used a variety of immune complex assays, with contradictory results (4-8).In the present study, sera of 92 unselected patients with PSS were examined for the presence of immune complexes by three techniques: the Raji cell radioimmunoassay (RCA) (9), the Clq binding assay (ClqBA) (lo), and pattern recognition on agarose gel electrophoresis (AGE) (1 1). Correlations with clinical and other laboratory features of PSS were sought by computer analysis of an extensive database compiled on these patients in our center as part of the American Rheumatism Association Medical Information System (ARAMIS) (12). PATIENTS AND METHODSSelection of patients. Single serum samples from 92 patients with PSS were examined; the group included 68 women and 24 men, ranging in age at study from 18 to 85 years (mean 48.3). Forty-eight of these individuals (32 women, 16 men) had diffuse scleroderma and 44 (36 women, 8 men) had the CREST syndrome (calcinosis, Raynaud's

European multicentre study to define disease activity criteria for systemic sclerosis. II. Identification of disease activity variables and development of preliminary activity indexes

“…However, both Seibold et al 35 and Benbassat et al 36 found hypocomplementaemia in 12% and 22.5% respectively—that is, in percentages not different from that detected by us (14%).…”

The complement system in systemic autoimmune disease

“…However, several early studies have reported abnormal complement activation and subendothelial deposition of immune complexes in patients with SSc [90,91]. Batal et al investigated renal histology in scleroderma renal crisis.…”

Decreased nailfold capillary density in Raynaud's phenomenon: a reflection of immunologically mediated local and systemic vascular disease?

“…This may result from endothelial damage mediated by immunological processes. Although circulating immune complexes are not considered as a major factor in the pathogenesis of scleroderma, increased levels have been described in MCTD and scleroderma.25 26 Autoantibodies may be pathogenic either by participation in immune complexes, by antibody-dependent cytotoxicity, or by in-vitro penetration of living cells, as is especially observed for nRNP antibodies.27 The decreased capillary density and increased number of enlarged loops in patients with immunological abnormalities argues for immunologically mediated vascular disease. Immunological processes may result in local inflammation.…”