Localization of fluorescein-labeled antinucleoside antibodies in glomeruli of patients with active systemic lupus erythematosus nephritis

Abstract

A B S T R A C T Renal tissues from two groups of patients were studied with fluorescein-labeled (Fl-) antibodies (Abs) to immunoglobulins, complement, and antibodies prepared in rabbits against BSA conjugate of 5-methyluridine (T) and cytidine (C), the latter two of which react specifically with denatured DNA. The first group consisted of 13 SLE patients, and the second consisted of 53 patients with non-SLE nephropathies. The data obtained from the two groups of patients were used for comparison, and they showed the following:(a) Fl-Abs to immunoglobulins and complement were bound in the glomeruli of tissues from all patients with active SLE glomerulonephritis characterized by deposits of foreign material in glomerular capillary walls (GCW). The fluorescent pattern was granular, corresponding to the distribution of the glomerular deposits, as seen by electron microscopy. Fl-Abs reactive with thymine and cytosine were bound in the GCW of eight of the nine patients with active SLE glomerulonephritis and showed the same granular distribution. The capacity of these latter Fl-Abs to stain the GCW was removed by absorption with the homologous antigen or denatured DNA.(b) Fl-Abs to immunoglobulins, complement, and pyrimidine bases of DNA did not react with the GCW of two SLE patients without clinical and histologic evidence of glomerulonephritis or with the sclerotic glomeruli of two uremic patients with chronic "burned out" lupus nephritis.(c) The glomeruli of 47 of the 53 patients with other nephropathies bound Fl-Abs to immunoglobulins and

Immunohistopathological analysis of immune-complexes related to anti-DNA antibodies in the serum and on the glomerulus in MRL/1 mice.

“…In order to increase the sensitivity of this method, we applied an immunoenzymatic electron microscopic method using peroxidase-labeled anti-uvDNA antisera, but the same findings were observed (manuscript in preparation; Kanemura et al). These observations seem to be not compatible with Andres et al (1). They demonstrated that FITC-labeled antisera reactive with thymine or cytosine were bound in the glomerular capillary walls of the patient with active SLE glomerular nephritis after treating with 0.02 M citrate buffer (pH 3.2) or 0.2 M NaCl.…”

Tolerance to DNA in (NZB × NZW)F1 Mice That Inherit an Anti-DNA VH as a Conventional μ H Chain Transgene but Not as a VH Knock-in Transgene

“…A consistently elevated anti-DNA Ab titer is a major diagnostic criterion in clinical assessment of potential SLE patients. In accordance, IgG anti-DNA Abs have been found deposited in the glomeruli of diseased human kidneys (3,4) and, when eluted, exhibit specificity for dsDNA. (NZB ϫ NZW)F 1 (BWF 1 ) mice are the classic animal model for SLE and closely mimic the human autoimmune disease with respect to autoantibody production, sex distribution, and the pathology of lupus nephritis (5,6).…”

Pauci-immune and Immune Glomerular Lesions in Kidney Transplants for Systemic Lupus Erythematosus

“…Generally, the severity of glomerular injury correlates with the severity of immune complex accumulation in proliferative lupus GN of native kidney (18)(19)(20)(21). Microvascular thrombosis (22), pauci-immune vasculitis-like lesions (23)(24)(25)(26)(27), and podocytopathy (28,29) are additional forms of glomerular injury described in native lupus nephritis.…”