Serologic markers of lupus nephritis in patients: use of a tissue-based ELISA and evidence for immunopathogenic heterogeneity

Abstract

SUMMARYIn order to assess the ability of various serologic assays to correlate with lupus nephritis, we analysed sera obtained from 60 patients with systemic lupus erythematosus (SLE), Patients were categorized as having active nephritis (group 1), active lupus without nephritis (group 2), inactive lupus with prior nephritis (group 3), or inactive lupus without prior nephritis (group 4), Three parameters were assessed including anti-dsDNA antibodies (Farr assay), immune complexes (Clq binding), and anti-Clq antibodies (salt-stable Clq binding). Additionally, glomerular binding activity (GBA) was measured using a new solid-phase immunoassay that detects immune elements by their ability to bind glomerular tissue. We found that patients with nephritis (group 1) exhibited higher mean values for each assay than patients in each of the other three groups {P = 0-001,0-009, 0-14, and 0-23 in the GBA, Clq, anti-dsDNA, and anti-Clq assays, respectively). The only assay which distinguished patients with nephritis (group 1) from patients having active disease without nephritis (group 2) was the GBA (mean 0-48 ± 0-09 versus 0-15 ± 0-04, P < 005), In terms of utility, all tests were specific for diagnosing nephritis among patients with lupus; however, only the GBA was reasonably sensitive. The information provided by the anti-dsDNA and Clq assays were not correlated with one another, nor additive to the GBA, Patients with false negative GBA tended to have received more intensive immunosuppression. The qualitative characteristics of GBA varied among patients with nephritis. These data suggest the pathogenesis of lupus nephritis is complex, and may be mediated by an array of immune elements. Moreover, the data indicate the potential utility for a broad tissue-based approach to detection of pathogenic immune elements over other, specific immunologic markers.

Nephritogenic Anti‐DNA antibodies regulate gene expression in MRL/lpr mouse glomerular mesangial cells

“…Affinity for glomerular antigens is a major determinant of the pathogenicity of anti‐dsDNA antibodies (18). Furthermore, there is excellent correlation between glomerular binding in vitro and renal disease in vivo (21, 22, 25). Accordingly, antibodies binding to both glomeruli and mesangial cells were defined as (potentially) pathogenic.…”

Circulating immune complexes levels correlate with the progression of canine leishmaniosis in naturally infected dogs

“…Several assay systems have been developed for detection of soluble complexes (Sobel et al, 1975;Hay et al, 1976;Digeon et al, 1977;, with different success rates. Previous studies have highlighted the importance of CIC in the pathogenesis of a variety of systemic disorders such as autoimmune diseases (Abrass et al, 1980;Nydegger and Davis, 1980;Bernstein et al, 1994), allergic diseases (Paganelli et al, 1981;Park and Nahm, 1998) and infectious diseases (Miles et al, 1993;Sengupta et al, 2002;Koraka et al, 2003). This suggests that CIC may be considered potential biomarkers of disease activity due to their diagnostic and prognostic value (Urbaniak-Kujda, 1996;Brunner and Sigal, 2001;Jaiswal et al, 2018;Thanadetsuntorn et al, 2018).…”

Diagnostic value of serum anti-C1q antibodies in patients with lupus nephritis: a meta-analysis

“…After full text identification, 93 citations were excluded for the following reasons: mechanism studies, quantitative data without cut-off value, statistical analysis without relative risk or odds ratio (OR), SLE patients without renal involvement were not included as a control group or two by two fourfold table cannot be constructed. Ultimately, only 25 studies8,[10][11][12]16,[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] met the eligibility criteria of the meta-analysis, among them 22 studies8,10,12,16,[25][26][27][28][29][31][32][33][34][35][36][37][38][40][41][42][43] had sufficient data for the analysis in LN diagnosis and 9 studies10,…”