Immune Complexes In Systemic Lupus Erythematosus Research Articles

Experiences of a battalion medical officer in the retreat to Dunkirk: IV.

The loss of tolerance and the presence of circulating autoantibodies directed against nuclear Ags is the hallmark of systemic lupus erythematosus (SLE). Many of these Ags are complexed with short, noncoding RNAs, such as U1 and Y1. The amount of U1 and Y1 RNA complexed with SLE patient Abs and immune complexes was measured in a cross-section of 228 SLE patients to evaluate the role of these RNA molecules within the known biochemical framework of SLE. The study revealed that SLE patients had significantly elevated levels of circulating U1 and/or Y1 RNA compared with healthy volunteers. In addition, the blood-borne RNA molecules were correlated with SLE disease activity and increased expression of IFN-inducible genes. To our knowledge, this study provides the first systematic examination of the role of circulating RNA in a large group of SLE patients and provides an important link with IFN dysregulation.

Evidence for the presence of autoantibodies to the collagen-like portion of C1q in systemic lupus erythematosus.

We investigated the connection between the C1q solid-phase binding assay (C1q SPBA) and double-stranded DNA antibodies, and analyzed the immune complex material in systemic lupus erythematosus (SLE) sera. Comparison with a new monoclonal assay for C1q-bearing immune complexes (the 242G3 assay) revealed that the immune complexes in SLE bind specifically to solid-phase C1q, and not to fluid-phase C1q. The C1q solid-phase binding activity sedimented as 7S IgG, was insensitive to DNase treatment, and could be selectively absorbed by C1q-coupled beads and by bovine serum albumin-anti-bovine serum albumin C1q beads, but not by DNA. Thus, antibodies to double-stranded DNA do not interfere in the C1q SPBA. Isolated IgG from SLE serum precipitated the collagen-like portions, and not the globular, Fc-recognizing portions, of C1q. F(ab')2 fragments of IgG from SLE patient serum were able to bind C1q. These data show that in SLE sera, especially in those with low levels of CH50 and C1q, autoantibodies that react with the collagen-like part of C1q are detectable. Since in the C1q SPBA, the C1q molecule is randomly fixed to the solid phase, we can detect not only immune complexes, but also antibodies that react with the collagen part of C1q; this may explain the high percentage of positive results for SLE sera in the C1q SPBA, in contrast to results of other immune complex assays.

Differences among immune complexes: association of C1q in SLE immune complexes with renal disease.

Studies that made use of multiple assay systems demonstrated increased levels of immune complexes (IC) in patients with systemic lupus erythematosus (SLE), but no consistent correlations of IC concentration to patterns or activity of disease have been observed. Furthermore, consistent associations between qualitative differences in IC and disease manifestations have been elusive. IC interaction with erythrocytes and mononuclear phagocytic cells is another variable in SLE that may also mediate some of the biological effects of IC. The present report concerns studies of the composition of purified IC obtained from individuals with SLE and other rheumatic diseases; a 64,000 dalton component identified as the A-B subunit of C1q was detected in purified IC from 27 of 51 SLE patients (53%). The presence of this 64,000 dalton component was not related to either IC concentration or to the serum C1q level. However, the presence of the C1q component in isolated SLE IC did correlate with the presence of renal disease (p less than 0.02). These observations are interpreted relative to a recently described kinetic model of IC clearance.

Plasma concentrations of complement split product C3d and immune complexes after procainamide induced production of antinuclear antibodies.

Seventeen patients treated with procainamide for cardiac ventricular arrhythmias were followed for up to 40 weeks. Immunological data as a clue to developing the systemic lupus erythematosus (SLE)-like syndrome was emphasized. Ten patients developed antinuclear antibodies (IgG or IgM), but no increase in the plasma concentration of the complement split product C3d or immune complexes, measured by two different methods, was demonstrated. This finding is in contrast to the high levels of both C3d and immune complexes in SLE. The discrepancy may be caused by a lack of immune complex mediated complement activation by the procainamide induced antibodies, or may be due to a difference in severity of disease. The acetylator phenotype of the patients was determined but due to the low frequency of fast acetylators no comparison of the immunological response of the two phenotypes could be done.

Acquired Factor XI Deficiency in Systemic Lupus erythematosus

A variety of coagulation abnormalities has been described in systemic lupus erythematosus (SLE). We report a unique SLE patient with an acquired factor XI deficiency. The low factor XI levels were not due to a classical coagulation inhibitor, but to a plasma factor (probably an immunoglobulin) that selectively bound factor XI. The factor XI deficiency improved after treatment with corticosteroids. Thus it is possible that in SLE immune complexes may bind clotting factors making them unavailable for use in the coagulation cascade.

Natural cytotoxicity in rheumatoid arthritis and systemic lupus erythematosus

Natural killer (NK) activity was investigated in 23 patients with rheumatoid arthritis (RA) and 7 patients with systemic lupus erythematosus (SLE). Killing of K-562 target cells by the peripheral blood lymphocytes of 7 patients with inactive RA did not differ from that observed in 18 controls. However, 16 patients with active RA and all patients with SLE exhibited impaired natural cytotoxicity. A strong correlation existed between reduced NK activity and elevated erythrocyte sedimentation rate but no correlations were observed with total peripheral blood lymphocyte counts, or total T, or Fcγ-receptor-positive lymphoid subpopulations. Impaired NK activity also correlated with elevated concentrations of circulating immune complexes in SLE, but not in RA. The contribution of circulating humoral factors to the observed decreases in natural cytotoxicity was analyzed by the addition of sera from different sources to normal lymphocytes either throughout the NK cell assay or by preincubation with the lymphocytes prior to the actual test. Little or no effect was observed with normal serum, with serum from patients with acquired hypogammaglobulinemia, or with serum from patients with RA. In contrast, SLE serum strongly inhibited NK activity at 37°C even when lymphocytes were simply pretreated and then throughly washed before the assay. The consequences of defective NK activity are largely unknown but may be associated with, although not necessarily a cause of, the enhanced rate of malignancy noted in SLE and RA.

The examination of antigens in highly purified immune complexes.

A combination of gel filtration and affinity chromatography was used for preparation of immune complexes (IC) from sera of individuals with systemic lupus erythematosus (SLE) and others with no apparent disease. Overlaying of gels with patient or normal sera, counterstaining with 125I-protein A and autoradiography showed besides immunoglobulins, the presence of 6 unidentified antigens with molecular weights below 42,000 dalton. They were not exclusively associated with SLE IC.

Viral immune complexes in systemic lupus erythematosus

Specimens of kidney, heart, lung, eye, skin, conjunctiva, choroid plexus and brain were obtained from a patient with systemic lupus erythematosus (SLE) post-mortem. The tissues were examined for immune-complex deposition by direct immunofluorescence utilizing antisera specific for IgG, IgA, IgE, IgM and the complement components Clq and C3. Tissues were also examined for C-type viral antigen by indirect immunofluorescence with an antisera raised to HEL-12 virus. Immune complexes were detected along basement membranes and/or in vessel walls of kidney, heart, lung, skin, conjunctiva and eye. HEL-12 viral antigen was detected in the same distribution as immunoglobulins and complement in all tissues. Preimmune serum did not mediate immunofluorescence and the reaction mediated by the anti-HEL-12 virus serum could be blocked by absorption with purified viral antigens. Two renal biopsies were obtained from a second SLE patient during clinical exacerbation and remission. Immunofluorescence analysis of the biopsy obtained during exacerbation showed 3 + deposition of immunoglobulin, complement and HEL-12 viral antigen. In contrast, the biopsy obtained 6 months later during remission showed trace -1 + immunofluorescence for HEL-12 viral antigen, immunoglobulin and complement. We conclude that HEL-12 viral antigen is a component of widely disseminated immune complexes in SLE, and that the disappearance of HEL-12 viral antigen occurs concomitantly with the loss of immune deposits.