Glomerular immune deposits in murine lupus models may contain histones

Two types of lupus mice, NZB/NZW F1 female hybrids and mice with graft-versus-host disease (GVHD), were studied. Histones H3 and H2A were detected by immunofluorescence in glomeruli of 22/22 proteinuric GVHD and 8/12 proteinuric NZB/W F1 female mice; in non-proteinuric animals, 3/5 GVHD and 2/27 NZB/W F1 female were positive. Using antibodies to histone peptides it was shown that mainly the N-terminal regions of histones H3 and H2A were exposed in glomerular deposits. Western blot analysis revealed antibodies to histone subfractions in sera of 33/34 lupus mice that developed proteinuria. This study provides evidence that histones are involved in the pathogenesis of lupus nephritis.