Article Text

Download PDFPDF

AA-03 Neuronal-surface P-antigen (NSPA), target of anti-ribosomal P autoantibodies, is expressed in proximal tubule epithelial cells (PTEC): potential role in lupus nephritis
  1. Marcela Bravo-Zehnder1,
  2. Patricia Gajardo1,
  3. Daniela Valenzuela1,
  4. Tomás Toledo1,
  5. Ángel Jurado1,
  6. Fabián Segovia1,
  7. Gonzalo Méndez2,
  8. Carlos Vio2,
  9. Loreto Massardo1 and
  10. Alfonso González1,2
  1. 1Center for Cell Biology and Biomedicine (CEBICEM), Faculty of Medicine and Science, Universidad San Sebastián, Santiago, Chile
  2. 2Center for Aging and Regeneration (CARE), Faculty of Biological Science, Pontificia Universidad Católica de Chile, Santiago, Chile


Background Patients with systemic lupus erythematosus (SLE) and anti-ribosomal P (anti-P) antibodies may present lupus psychosis, cognitive impairment and lupus nephritis (LN). Our group provided a molecular mechanism to explain the neuronal alterations in SLE identifying the neuronal-surface P-antigen (NSPA) as an anti-P target involved in the regulation of synaptic glutamatergic transmission (Bravo-Zehnder et al. A and R 2015; Segovia-Miranda et al. A and R 2015). There is evidence suggesting that anti-P and anti-dsDNA antibodies have the potential to perturb the function of renal cells in addition to complement activation. The mechanism of anti-P association with lupus nephritis remains unclear. It is possible that direct anti-P interaction with cell surface components activates intracellular signalling pathways resulting in renal cell damage. As a first approximation to this hypothesis we study whether and where NSPA is expressed in the kidney.

Methods NSPA expression was assessed by RT-PCR, immunoblot and anti-NSPA immunohistochemistry in C57WT mice, ß-galactosidase (ß-gal) histochemistry staining in transgenic mice bearing a LacZ gene under the promotor of NSPA gene and anti-P staining in the surface of primary cultures of PTEC and the human kidney cell line HK2. NSPA polarized distribution was studied in Madin-Darby canine kidney (MDCK) cells transfected with NSPA-GFP expression plasmid. The pathogenic potential of anti-P antibodies was analyzed by immunizing C57WT and NSPAKO mice with recombinant P0 ribosomal bearing (P0wt) or not the P epitope (P0tr) and testing anti-P and anti-dsDNA presence, proteinuria and renal pathology by histochemistry and electron microscopy.

Results NSPA is expressed in PTEC cells and display a mainly apical distribution in vivo and in vitro, including the transfected MDCK cells. Both P0wt and P0tr generated high levels of anti-P antibodies and some mice also developed anti-dsDNA antibodies. Mice presented mild proteinuria at 6 months of immunization. C57WT and NSPAKO mice immunized with either P0wt or P0tr also displayed perivenular lymphocytic infiltration, a mild renal pathology change. In addition, NSPAKO mice, even in absence of anti-dsDNA, showed mesangial electron dense-deposits with discrete effacement of foot processes.

Conclusions NSPA is expressed in both PTEC and polarized MDCK epithelial cells with a polarized distribution that precludes direct interaction with circulating anti-P antibodies, which might access to this target only after glomerular filtration. Circulating anti-P can associate with mild kidney damage independently of NSPA expression, at least in non-lupus prone mice.

Acknowledgements CONICYT Basal grant PFB12/2007 and FONDECYT Grant 1160513.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.