Background/Purpose: Circulating anti-phosphoribosomal protein antibodies (anti-Ribos.P) were found to be associated with lupus nephritis. We have assessed the direct role of anti-Ribos.P in the development of glomerulonephritis  in-vitro and in animal models. 

Methods: NZBxW/F1 lupus prone mice were immunized with recombinant Ribos.P0 (rRibos.P).  The following lupus parameters were analyzed: autoantibodies screen directed to Ribos.P, dsDNA and Sm by ELISA. Proteinuria was determined by protein-sticks, kidney pathology by H&E staining and  immunoglobulin deposits by immunofluorescence. Anti-Ribos.P deposited in the  glomerular mesangium were eluted from the kidney. Anti-Ribos.P monoclonal Ab was prepared from the rRibos.P immunized NZBxW/F1 mice by hybridoma technology.  . MAPKs expression was analyzed by MAPKs protein-array and confirmed by real-time PCR. To elucidate whether anti-Ribos.P induce glomerulonephritis, naïve C3H mice were immunized with recombinant Ribos.P0 (rRibos.P) and the glomerulonephritis was followed up as described above. 

Results: Our data demonstrate that  rRibos.P0 immunized NZBxW/F1 mice  developed accelerated glomerulonephritis characterized by anti-Ribos.P deposition in the glomerular mesangium . Primary mesangial cells exposed to mouse anti-Ribos.P mAb originated from the immunized lupus mice and to human anti-Ribos.P Abs , induced p38a MAPK expression. Moreover, naïve C3H/Hen mice immunized with rRibos.P0 developed experimental lupus nephritis manifested by circulating autoantibodies directed to Ribos.P, dsDNA, Sm and glomerulonephritis with anti-Ribos.P depositions. In conclusion,   Our data show for the first time that anti-Ribos.P are nephritogenic autoantibodies, as illustrated by in-vitro and in-vivo experiments: a) They accelerate the development of glomerulonephritis in lupus prone mice; b) They induce nephritis in naïve mice. c) Anti-Ribos.P Abs trigger MAPKs expression in primary mesangial cells.

Conclusion: These data contribute a direct mechanistic link between anti-Ribos.P and nephritis in lupus mice.