Prolonged membranous lupus nephritis with change of anti-ssDNA antibody titer and repeated renal relapse

Abstract

We report a case of a 44-year-old woman with nephrotic syndrome who underwent renal biopsy three times. On each occasion, light microscopy showed membranous nephropathy with mild to moderate thickening of the glomerular capillary walls. Immunofluorescence microscopy showed predominant deposition of immunoglobulin (Ig) G, IgG1, IgG2, IgG3, and IgG4; C3; and C1q along the glomerular capillary walls and deposition of IgM and IgA in some parts of the walls. Electron microscopy revealed the accumulation of electron-dense deposits in the mesangium and the subepithelial area of the glomerular basement membrane. Virus-like particles were detected in the subendothelial cells in all three biopsy specimens. A definitive diagnosis of systemic lupus erythematosus (SLE) was made at the time of the second admission, when she was 31 years old. A diagnosis of membranous lupus nephritis was then made on the basis of the pathological and clinical findings. A change in anti-single-stranded (ss)DNA antibody titers was of particular interest in this patient. Occasional small increases in anti-double-stranded (ds)DNA antibody were found, but increased anti-ssDNA antibody titers occurred before there was any elevation of urinary protein during renal relapse, and a sustained increase in the titers was shown subsequently. Hypocomplementemia occurred in parallel with the increase of anti-ssDNA antibody. Immunosuppressive therapy with steroid promptly eliminated anti-dsDNA antibody, but anti-ssDNA antibody remained positive. The patient had normocomplementemia and proteinuria was absent. Later, anti-ssDNA antibody decreased. Renal function has remained in the normal range for 20 years.

An unusual case of loin pain and nephritis

“…An interesting point is that this patient only had high anti-dsDNA titre and low C3 level 2 years after initial presentation. Yumura et al reported a 44-year-old woman with similar presentation in Japan [15]. Our patient first exhibited nephrotic syndrome at the age of 14, when she had borderline titre of anti-dsDNA and had no hypocomplementemia.…”

“…Although most patients with lupus nephritis exhibit active lesions histologically with high anti-dsDNA titre, patients with membranous lupus nephritis may have less active histological findings and are often negative for anti-dsDNA [15,16]. The titre of anti-single-stranded DNA (anti-ssDNA) antibody was suggested by some authors to better co-relate with renal disease activity than anti-dsDNA [15,17]. However, studies in this field are limited, and hopefully, more information will be available in the future.…”

“…The clinical course of MN in children is considered to be favorable in general [4]. The maintenance of renal remission with corticosteroid and immunosuppressant is important to prevent deterioration of renal function [4,15].…”

A Case with Membranous Lupus Nephritis Developing after a Twenty-year Remission of Membranoproliferative Glomerulonephritis

“…Some patients with "full-house" nephropathy were found to develop SLE several years later (5,6). In some SLE patients the histopathologic features of lupus nephritis on renal biopsy were not observed, while accompanying IgA nephropathy was diagnosed (7).…”

A Novel Method for Real-Time, Continuous, Fluorescence-Based Analysis of Anti-DNA Abzyme Activity in Systemic Lupus

“…However, we have chosen to investigate anti-ssDNA antibodies, which present in 30–70% of patients, based on data indicating that they are hydrolytic, nephritogenic, and may serve as strong predictors of flare [3, 4, 26–28]. The significance of anti-ssDNA antibodies in SLE is further supported by data indicating that they are still present after treatment with immunosuppressive therapy which eliminates anti-dsDNA antibodies, investigations in mouse models of nephritogenic lupus in which only anti-ssDNA antibodies were found, and findings that some anti-dsDNA antibodies are not pathogenic [6, 7, 19, 27, 29, 30]. …”