title: Prognostic value of anti-CRP antibodies in lupus nephritis in long-term follow-up.
abstract: BACKGROUND
  Autoantibodies against monomeric C-reactive protein (anti-CRP-Ab) observed in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) were suggested to be associated with active LN and a poor response to therapy during short-term follow-up. The aim of this study was to confirm this finding and to investigate the prognostic value of anti-CRP-Ab in patients with LN during long-term follow-up.
  
  
  METHODS
  Sera of 57 SLE patients (47 women, 10 men) with biopsy proven LN and 122 healthy individuals were analyzed for the presence of anti-CRP-Ab by in-house ELISA. Anti-CRP-Ab levels were studied in relation to routine laboratory tests, urine analysis, levels of C3, C4, other immunological markers and the overall disease activity as assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The prognostic value of anti-CRP-Ab was tested in a subgroup of 29 newly diagnosed LN patients (median follow-up 5.9 years). Response to therapy at various time points was assessed with respect to baseline anti-CRP-Ab levels. At least partial response in the first/second year of treatment was considered as a "favorable outcome", while non-response, renal flare or end stage renal disease were considered as "unfavorable outcome".
  
  
  RESULTS
  Anti-CRP-Ab were only detected in patients with active renal disease and their levels correlated with SLEDAI (rs = 0.165, p = 0.002). The time to response was shorter in patients being anti-CRP-Ab negative at baseline compared to anti-CRP-Ab positive patients, p = 0.037. In the second year of therapy, baseline anti-CRP-Ab positivity was a significant predictor of "unfavorable outcome" (OR [95% CI] = 15.6 [1.2-771]; p = 0.021). The predictive value of "baseline anti-CRP positivity" further increased when combined with "non-response to therapy in the first year". Baseline anti-CRP-Ab positivity was not a predictor of "unfavorable outcome" at the end of follow-up, (OR [95% CI] = 5.5 [0.6-71.1], p = 0.169).
  
  
  CONCLUSIONS
  Baseline serum levels of anti-CRP-Ab seem to be a strong risk factor for a composite outcome of non-response, renal flare or end stage renal disease after two years of standard treatment of LN. The response to therapy seems to be delayed in anti-CRP-Ab positive patients.
authors.affiliation: Department of Nephrology, General University Hospital and First Faculty of Medicine, Charles University, Prague, U Nemocnice 2, 12808 Prague 2, Czech Republic. satu.pesickova@gmail.com.|Dialcorp, Hemodialysis unit, Prague, Ohradni 1368, 14000 Prague 4, Czech Republic. satu.pesickova@gmail.com.
authors.forename: Satu Sinikka
authors.initials: SS
authors.lastname: Pesickova
authors.affiliation: Department of Nephrology, General University Hospital and First Faculty of Medicine, Charles University, Prague, U Nemocnice 2, 12808 Prague 2, Czech Republic. romana.rysava@vfn.cz.
authors.forename: Romana
authors.initials: R
authors.lastname: Rysava
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University, Prague, Katerinska 32, 12808 Prague 2, Czech Republic. mleni@centrum.cz.
authors.forename: Martin
authors.initials: M
authors.lastname: Lenicek
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University, Prague, Katerinska 32, 12808 Prague 2, Czech Republic. vitek@cesnet.cz.|Fourth Department of Medicine, General University Hospital and First Faculty of Medicine, Charles University, Prague, U Nemocnice 2, 12808 Prague 2, Czech Republic. vitek@cesnet.cz.
authors.forename: Libor
authors.initials: L
authors.lastname: Vitek
authors.affiliation: Third Department of Medicine, General University Hospital and First Faculty of Medicine, Charles University, Prague, U Nemocnice 2, 12808 Prague 2, Czech Republic. eliska.potlukova@usb.ch.|Division of Internal Medicine, University Hospital Basel, Basel, Spitalstrasse 21, 4031 Basel, Switzerland. eliska.potlukova@usb.ch.
authors.forename: Eliska
authors.initials: E
authors.lastname: Potlukova
authors.affiliation: Department of Nephrology, General University Hospital and First Faculty of Medicine, Charles University, Prague, U Nemocnice 2, 12808 Prague 2, Czech Republic. zd.hruskova@seznam.cz.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Hruskova
authors.affiliation: Department of Nephrology, General University Hospital and First Faculty of Medicine, Charles University, Prague, U Nemocnice 2, 12808 Prague 2, Czech Republic. eva.jancova@volny.cz.
authors.forename: Eva
authors.initials: E
authors.lastname: Jancova
authors.affiliation: Department of Pathology, Institute for Clinical and Experimental Medicine, Prague, Videnska 1958/9, 140 21 Prague 4, Czech Republic. evhn@medicon.cz.
authors.forename: Eva
authors.initials: E
authors.lastname: Honsova
authors.affiliation: Institute of Rheumatology, First Faculty of Medicine, Charles University, Prague, Na Slupi 4, 128 50 Prague 2, Czech Republic. zavada@revma.cz.
authors.forename: Jakub
authors.initials: J
authors.lastname: Zavada
authors.affiliation: Division of Internal Medicine, University Hospital Basel, Basel, Spitalstrasse 21, 4031 Basel, Switzerland. Marten.Trendelenburg@unibas.ch.|Laboratory of Clinical Immunology, Department of Biomedicine, University Hospital Basel, Basel, Spitalstrasse 21, 4031, Switzerland. Marten.Trendelenburg@unibas.ch.
authors.forename: Marten
authors.initials: M
authors.lastname: Trendelenburg
authors.affiliation: Department of Nephrology, General University Hospital and First Faculty of Medicine, Charles University, Prague, U Nemocnice 2, 12808 Prague 2, Czech Republic. vladimir.tesar@vfn.cz.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tesar
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008181:Lupus Nephritis / Q000097:blood / Q000276:immunology*; D008297:Male; D011379:Prognosis; D012720:Severity of Illness Index
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D002097:C-Reactive Protein