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Background and objectives: Neuropilin-1 (NP-1), a functional vascular endothelial growth factor (VEGF) receptor, is important in the priming of resting T cells and contributes to the development of peripheral tolerance. Semaphorins, a family of axon guidance molecules, has been found to be involved in regulating the immune system.The aim of this study was to explore the involvement of NP-1 and semaphorins in lupus glomerulonephritis (LGN).Methods: Twelve kidney biopsies from LGN patients and five normal biopsies were examined in this study. In addition, eight biopsies from patients with primary nephropathy and proteinuria were included serving as a disease control group. Biopsies were stained with anti-VEGF, NP-1, and semaphorins. The Image Pro-Plus software was used to measure the intensity and extent of staining. The correlation with clinico-pathological parameters was evaluated.Results: VEGF expression was slightly higher in LGN. NP-1 and semaphorins were stained with significantly higher intensity in LGN when compared with both the normal and the disease control groups. NP-1 deposits were found only in damaged glomerulus areas and positively correlated with clinico-pathological parameters of renal disease (a statistical trend). However, the semaphorins were found in inverse correlations.Discussion: Being present in normal and slightly increased in diseased glomeruli, VEGF is considered protective during inflammation. Increased NP-1 expression in LGN may intensify the possible protective effect of VEGF, thereby preventing endothelial damage. However, one should consider the possibility that increased NP-1 expression is harmful and could play a role in the damage of LGN. NP-1 is suggested to be a reliable marker differentiating focal versus diffuse LGN. Semaphorin 3A can serve as a histological marker for tubular damage. The altered ability of kidneys to secrete semaphorins during advanced renal damage may in part explain its inverse correlation with renal function. Further work is needed in order to better understand the role of NP-1 and semaphorins in LGN. [ABSTRACT FROM AUTHOR]

The benefit of combining quinacrine (Qn) with hydroxychloroquine (HCQ) in the treatment of systemic lupus erythematosus (SLE) was previously re-evaluated by us. In our current study we observed that, in 11 active SLE patients (SLEDAI score 5-12), the addition of Qn (100mg/day) to their existing ongoing therapeutic regimens resulted in a significant attenuation of their previously persistent anticardiolipin antibody (aCL) response. This was in comparison with a matched non-Qn treated control group composed of 14 randomly chosen aCL-positive SLE patients with a similar SLEDAI score 6-10. Prior to Qn treatment the therapeutic regimens of 12 months' duration, included in all cases HCQ (400mg/day), in many cases prednisone (P, 10-20mg/day) and in some additional cases immunosuppressive drugs. SLEDAI scores and aCL levels were monitored during the entire follow-up period which totaled 24 months in the study group and 15-18 months in the controls. Along with the beneficial effect of the added Qn on SLEDAI scores, aCL disappearance was documented in eight of 11 patients and remained negative during 8-12 months of follow-up (P =0.004), compared with such a change in only three of 14 non-Qn treated aCL-positive patients (P =0.18). We conclude that the added Qn treatment to former established therapeutic protocols may eliminate aCL response in SLE patients. Whether this agent's effect is permanent needs further elucidation. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that IgG autoantibodies derived from SLE patients are capable of penetrating into nuclei of living COLO-16 cells, in vitro. To address the possible correlation in Lupus Erythematosus (LE) between the in vivo ANA binding to nuclei of epidermal cells and the presence of intranuclear penetrating antibodies in sera of those patients, 25 consecutive patients were studied. Out of 25 skin biopsies, 11 specimens (8 of SLE and 3 of DLE) showed by immunofluorescent microscopy extensive in vivo presence of IgG in epidermal nuclei, whereas all sera of these patients stained nuclei of living COLO-16 cells, in vitro. Such penetration was also observed in additional 6/25 sera of patients, but with in vivo negative biopsies. This in vitro nuclear binding, which was unrelated to clinical symptoms of patients or their serological autoantibody profile and titer, was reproduced following cross-linking of intracellular protein by PLP fixation. Likewise, western blotting (immunoblotting) analysis, demonstrated the intranuclear presence of IgG in all in vitro intranuclear IgG staining sera. Furthermore, this in vitro presence, which neither affects cell viability nor DNA synthesis, is time-dependent and of a transient nature: nuclear staining disappears within 48 h following removal of the penetrating sera from medium. In conclusion, since the COLO-16 in vitro assay mirrors exactly the in vivo situation, and because of its higher sensitivity, it provides an excellent tool for the study of non-degraded autoantibody penetration into the nuclei of living cells. [ABSTRACT FROM PUBLISHER]