Anti-DNA antibodies form immune deposits at distinct glomerular and vascular sites

D. V. Vlahakos, M. H. Foster, S. Adams, M. Katz, A. A. Ucci, K. J. Barrett, S. K. Datta, M. P. Madaio*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

189 Scopus citations

Abstract

To investigate the capacity of lupus autoAb to produce glomerular immune deposits (ID) and nephritis, 24 murine monoclonal (m) anti-DNA antibodies (Ab), derived from either MRL-lpr/lpr, SNF1 or NZB lupus-prone mice and selected based on properties shared with nephritogenic Ig, were administered i.p. (as hybridomas) and i.v. (as purified Ig) to normal mice; at least four mice/mAb were evaluated. Three general patterns of immune deposit formation (IDF) were observed: extracellular 1D within glomeruli (± blood vessels. N = 8); intranuclear ID (N = 5); or minimal or no ID (A = 11). The four MRL m anti-DNA Ab that produced significant extracellular ID demonstrated different disease profiles including: (a) mesangial and subendothelial ID with anti-basement membrane staining, associated with proliferative glomerulonephritis, PMN infiltration, and proteinuria: (b) diffuse fine granular mesangial and extraglomerular vascular ID, associated with proliferative glomerulonephritis and proteinuria: (c) dense intramembranous ID and intraluminal ID, associated with capillary wall thickening, mesangial interposition and expansion, aneurysmal dilatation and intraluminal occlusion of glomerular capillary loops, and heavy proteinuria; and (d) mesangial and extraglomerular vascular ID, associated with mild segmental mesangial expansion, without proteinuria. These MRL mAb were derived from four different mice, and they had variable pIs and isotypes. They all cross reacted with multiple autoantigens (autoAg), however, their autoAg binding profiles were distinguishable. Among the SNF1 derived mAb, four produced histologically and clinically indistinguishable disease characterized by diffuse mesangial and capillary wall ID, associated with cellular proliferation/infiltration and proteinuria. Three of the four mAb were derived from the same mouse and were clonally related; they were: IgG2b with SWR allotype, relatively cationic, highly cross reactive with similar Ag binding patterns, idiotypically related and encoded by identical V(H) and nearly identical V(L) sequences. We conclude that both the capacity of lupus autoAb to form ID and the location of IDF are dependent on properties unique to individual Ig. The results also indicate that the Ag binding region of the autoAb is influential in this process, and they suggest that multiple Ab-Ag interactions contribute to IDF in individuals with lupus nephritis. Furthermore, these observations raise the possibility that the pathologic and clinical abnormalities resulting from these interactions are influenced by the location of IDE, and that the dominant interaction, in a given individual, may be highly influential in the phenotypic expression of nephritis.

Original languageEnglish (US)
Pages (from-to)1690-1700
Number of pages11
JournalKidney international
Volume41
Issue number6
DOIs
StatePublished - 1992

ASJC Scopus subject areas

  • Nephrology

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