Antinuclear Antibody Crossreacts with IgG Fc Fragments: The Nature of Immune Complexes in Lupus Nephritis in Humans and NZB/WF1 Mice

Abstract

SummaryImmunofluorescence studies from 14 patients with lupus nephritis (LN) revealed granular IgG deposits in the glomeruli. The IgG deposits were dissociated after incubation with human IgG and IgG Fc fragments (frg), but not with sheep or rat-gammaglobulin or human IgG (ab′)2, indicating that human IgG especially Fc frg, played an important role in the dissociation and that the immune complexes LN were composed of IgG rheumatoid factor (RF).These results were interpreted as suggesting that a certain IgG antinuclear antibody (ANA) possessed RF reactivity. To confirm this, the sera from the 14 cases of lupus patients described above were tested for ANA activity by indirect immunofluorescence following incubation with IgG of various species including human, rabbit, and rat and human IgG F (ab′)2 or human IgG Fc frg by indirect immunofluorescence. ANA activity disappeared in 9 out of 14 sera from SLE patients after incubation with human IgG and Fc frg. The ANA activity, however, did not disappear following incubation with the other species of IgG and human IgG F (ab′)2.Similar experiments were performed in NZB/WF1 mice. Granular deposits of mouse IgG were present along the glomerular capillary walls of 6- to 12-month-old mice. Using these kidney sections, the dissociation test was performed by incubating with mouse IgG, mouse Fc frg, rat IgG, rat Fc frg, human and rabbit Cohn fraction-II (FII), DNA, nucleohistone and PBS for 6 hours changing in PBS. The IgG deposits in the glomeruli disappeared or decreased following incubation with mouse and rat IgG, especially with mouse and rat Fc frg, but not with human, rabbit FII, DNA, nucleohistone and PBS.ANA activity in the NZB/WF1 mice serum or kidney eluate disappeared after incubation with mouse IgG or Fc frg, rat IgG or Fc frg, DNA and nucleohistone, but not with human or rabbit FII.These results indicated that the immune complexes found in human and NZB/WF1 mice were composed of IgG and IgG ANA crossreacting with their own denatured IgG Fc portion.