Background/Purpose: Autoantibodies targeting ribosomal phosphoproteins (anti-Ribos.P) are detected in the sera of  10-45%  patients with  neuropsychiatric-systemice-lupus-erythemathosus-(NPSLE) and correlate with disease-activity. Intracerebroventricular administration of anti-Ribos.P induce depression like behavior in naïve mice. We assessed the capability of anti-Ribos.P to penetrate neuronal cells and affect the cellular function.

Methods: The penetration of human affinity purified anti-Ribos.P Abs  into cultured neuronal cells, was shown by confocal microscopy. Endothelial Cells (HUVEC) were used as control  Identification of the molecule targeted by anti-Ribos.P Abs was performed by screening a high content human cDNA-library The cross-reactivity between ribosomal-P0 and the identified neuron-growth-associated-protein-GAP43 was done by ELISA. Inhibition of neuronal cell proliferation was carried out by Bromodeoxyuridine-(BrdU).

Results: We show herein the penetration of human anti-Ribos.P Abs into human neuronal cells and rat hippocampal cells cultures, in-vitro. These Abs bind mouse brain sections of hippocampus, dentate and amygdala. Moreover, anti-Ribos.P Abs target neuronal cells through GAP43 binding. The anti-Ribos.P binding to mouse hippocampus, dentate and amygdala was prevented by GAP43 protein. Interestingly, GAP43 inhibited in a dose- dependent manner the anti-Ribos.P binding to ribosomal-P0 recombinant protein, indicating a cross-reactivity between the ribosomal-P0 protein and GAP43. Furthermore, anti-Ribos.P Abs reduced neuronal cells proliferation activity, in-vitro p<0.001) whereas GAP43 prevented this inhibitory activity by 7.6 times.    

Conclusion: Anti-Ribos.P Abs penetrate neuronal cells in-vitro by targeting GAP43. Ribos.P0 cross-react with GAP43. Anti-Ribos.P Abs inhibit neuronal-cell proliferation. Our data contribute to deciphering the mechanism for anti-Ribos.P Abs pathogenic activity in NPSLE.