Immunopathologic Studies of Systemic Lupus Erythematosus. II. Antinuclear Reaction of γ-Globulin Eluted from Homogenates and Isolated Glomeruli of Kidneys from Patients with Lupus Nephritis *

Abstract

Summary. The yG-globulin eluted at acid pH from kidney cortex homogenates and isolated glomeruli of five of six patients with lupus nephritis was found to exhibit antinuclear activity, which was not dependent on presence of fresh human serum. Specificity, as demonstrated by absorption of antinuclear activity, was related to nucleoprotein in three glomerular acid eluates and to DNA in two acid eluates as well as in a deoxyribonuclease digest of disrupted glomeruli in one patient. Antinuclear activity was not found in acid eluates of kidneys from two patients with chronic liver disease and chronic discoid lupus, respectively, and one with lupus nephritis. These patients had a low titer of serum antinuclear factor and lesser amounts of kidney bound immunoglobulins. The presence of antinuclear activity in eluates of kidneys appeared to correlate with the amount of glomerular bound immunoglobulin and the level of antinuclear antibodies in serum. These findings suggest that in lupus nephritis, part of the glomerular bound immunoglobulin is derived from serum antinuclear factors possibly deposited as immune complexes. IntroductionThe definition of immunoglobulin deposits in lupus kidneys has been approached by techniques applicable to dissociation of antigen-antibody complexes. Sections of lupus nephritis kidneys washed at acid pH (3.0 to 3.2) were found to lose considerable staining for y-globulin in glomerular and vas-

Deposition of antibodies to the collagen‐like region of C1Q in renal glomeruli of patients with proliferative lupus glomerulonephritis

“…Kidney tissues were obtained at autopsy, regardless of the cause of death, from 13 patients (designated K1 through K13) with the established diagnosis of SLE. These 13 specimens included 8 from the University of Washington Medical Center or from 1505 affiliated hospitals, as approved by the Human Subjects Committee. Three samples were obtained through the Western Division of the Cooperative Human Tissue Network, and 2 were from other medical centers.…”

“…Second, increasing levels of antibodies to dsDNA may herald an exacerbation of the renal disease (4-6). Third, in the pioneering studies of Koffler and colleagues and of Krishnan and Kaplan, antibodies to dsDNA were recovered from the glomeruli of SLE patients who had died (7)(8)(9).…”

Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2)

“…Relevant information is lacking on the composition and characteristics of autoantibodies on the basis of an in vivo characterization of Igs microeluted directly from renal biopsies; until recently, 11 studies addressing composition and quality of renal autoantibodies in human LN were limited to postmortem kidney tissues. 18,19 Technologies are now available that allow minute isolation of glomeruli from fresh renal biopsies and characterization of autoantibodies/ antigens. Laser microdissection and proteomics already have been successfully used to widen the spectrum of podocyte antigens in LN 11 and other primary autoimmune GNs.…”

The Role of B-Cells and B-Cell Targeted Therapies in Lupus Nephritis

“…These antibodies were the first to be found in both humans with lupus nephritis and animal models of the disease. 35,36 They are implicated in all postulated mechanisms of disease; however the true extent of the pathogenicity of anti-DNA antibodies is unclear. SLE patients have a dysregulation in apoptosis with decreased clearance of apoptotic bodies that are released in the serum.…”