Renal deposition of alpha interferon in systemic lupus erythematosus

Abstract

Earlier studies from several laboratories showed that interferon-(x (IFN-ax) is present in the sera of a large percentage of patients with systemic lupus erythematosus (SLE). We now report the detection of IFN-ax by indirect immunofluorescence in renal sections of three patients with SLE but not in six control kidneys. The immunofluorescence reaction was mediated by three hyperimmune antisera to IFN-at raised in three different species, but not by any preimmune serum. The reaction was specifically blocked by absorption of the anti-IFN-a sera with purified IFN-a made by recombinant DNA techniques or with IFN-ot isolated from the serum of an SLE patient, but not by bovine serum albumin or human immunoglobulin G. In contrast, antisera to IFN-3 or IFN-y did not mediate immunofluorescence. The pattern of IFN-at deposition resembled that seen with anti-human immunoglobulin G, suggesting association with immune complexes. Immune complexes were then preparatively eluted from the homogenate of an SLE kidney by treatment with buffer at pH 2.8. Biologically active IFN was found in this eluate and was demonstrated to be IFN-cx by specific neutralization with IFN antisera. These results extend the specific association of IFN-ot with SLE.

Distinct Functions of Autoantibodies Against Interferon in Systemic Lupus Erythematosus: A Comprehensive Analysis of Anticytokine Autoantibodies in Common Rheumatic Diseases

“…In rheumatic diseases, autoantibodies against one cytokine or a small group of cytokines have been reported (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), but their spectrum and clinical impact remain largely unknown. Autoantibodies against type I and type II interferons have been reported in the sera of up to 27% of patients with systemic lupus erythematosus (SLE) (8)(9)(10)(11). Their impact on the interferon gene expression signature and the pathogenesis of SLE is unclear, but their potential to influence interferon signaling, disease activity, and the response to biologic therapies could be great (11).…”

Production of interferon by peritoneal cells of several inbred mouse strains

“…I already mentioned lupus erythematosus. I n the blood of many patients the acid labile form of alfa-interferon has been described (HOOKS et al 1979, PANEM et al 1982, YTTERBERG and SCHNITZER 1982. It is the same form of I F N which was found by BOCCI et al in small amounts in the plasma of healthy volunteers (1985).…”

Hypothetical review: thymic aberrations and type-I interferons; attempts to deduce autoimmunizing mechanisms from unexpected clues in monogenic and paraneoplastic syndromes

“…Surprisingly, we found broadly-reactive NAAbs against the IFN-as, usually at high titres, in~70% of these patients [36,43]; • Stimulation of IFN-a production by DNA:Ab complexes [35,36]; • Neutralizing anti-IFN-a autoantibodies in occasional patients [44][45][46]. C. High titre neutralizing anti-IFN autoantibodies in certain autoimmune diseases (see Table 3).…”

“…Type I IFNs are implicated generally in autoimmunization by assorted apparently confusing findings [35][36][37][38][39][40][41][42][43][44][45][46], and especially in SLE (Box 1; see Section VII). Indeed, several autoimmune disorders may follow prolonged anti-viral therapy with recombinant IFN-a2, (e.g.…”