Antiphospholipid Antibodies in Lupus Nephritis

PLoS One. 2016 Jun 23;11(6):e0158076. doi: 10.1371/journal.pone.0158076. eCollection 2016.

Abstract

Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE). It remains unclear whether antiphospholipid antibodies (aPL) alter the course of LN. We thus investigated the impact of aPL on short-term and long-term renal outcomes in patients with LN. We assessed levels of aPL cross-sectionally in SLE patients diagnosed with (n = 204) or without (n = 294) LN, and prospectively in 64 patients with active biopsy-proven LN (52 proliferative, 12 membranous), before and after induction treatment (short-term outcomes). Long-term renal outcome in the prospective LN cohort was determined by the estimated glomerular filtration rate (eGFR) and the Chronic Kidney Disease (CKD) stage, after a median follow-up of 11.3 years (range: 3.3-18.8). Cross-sectional analysis revealed no association between LN and IgG/IgM anticardiolipin or anti-β2-glycoprotein I antibodies, or lupus anticoagulant. Both aPL positivity and levels were similar in patients with active LN and non-renal SLE. Following induction treatment for LN, serum IgG/IgM aPL levels decreased in responders (p<0.005 for all), but not in non-responders. Both at active LN and post-treatment, patients with IgG, but not IgM, aPL had higher creatinine levels compared with patients without IgG aPL. Neither aPL positivity nor levels were associated with changes in eGFR from either baseline or post-treatment through long-term follow-up. Moreover, aPL positivity and levels both at baseline and post-treatment were similar in patients with a CKD stage ≥3 versus 1-2 at the last follow-up. In conclusion, neither aPL positivity nor levels were found to be associated with the occurrence of LN in SLE patients. However, IgG aPL positivity in LN patients was associated with a short-term impairment of the renal function while no effect on long-term renal outcome was observed. Furthermore, IgG and IgM aPL levels decreased following induction treatment only in responders, indicating that aPL levels are affected by immunosuppressive drugs in a response-dependent manner.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Antiphospholipid / blood
  • Antibodies, Antiphospholipid / immunology*
  • Biopsy
  • Cross-Sectional Studies
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunoglobulin M / blood
  • Immunoglobulin M / immunology
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / epidemiology
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Nephritis / diagnosis
  • Lupus Nephritis / drug therapy
  • Lupus Nephritis / epidemiology*
  • Lupus Nephritis / immunology*
  • Male
  • Middle Aged
  • Patient Outcome Assessment
  • Public Health Surveillance
  • Sweden / epidemiology
  • Young Adult

Substances

  • Antibodies, Antiphospholipid
  • Immunoglobulin G
  • Immunoglobulin M

Grants and funding

This study was supported by grants from the Swedish Research Council, Swedish Rheumatism Association, King Gustaf V’s 80-year Foundation, Swedish Heart-Lung Foundation, Foundation in memory of Clas Groschinsky, Stockholm County Council and Karolinska Institutet Foundations.