Antiphospholipid Antibodies in Lupus Nephritis

Ioannis Parodis,Elisabet Svenungsson,Laurent Arnaud,Birgitta Sundelin,Iva Gunnarsson,Vivianne Malmström,Jakob Gerhardsson,Agneta Zickert,Jose Crispin

doi:10.1371/journal.pone.0158076

Ioannis Parodis, Elisabet Svenungsson + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0158076

Copy DOI

Journal: PloS one	Publication Date: Jun 23, 2016
Citations: 26	License type: CC BY 4.0

Affiliation: Karolinska University Hospital, Karolinska Institutet

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.

Highlights

Antiphospholipid antibodies constitute a heterogeneous family of antibodies against phospholipids or phospholipid-binding proteins
Our findings suggest that IgG aPL might contribute to an impaired renal function during a Lupus nephritis (LN) flare despite the absence of APLN, and raise the hypothesis that aPL may have a pathogenic role in the kidney, resulting in renal function deterioration
APL levels decreased in LN patients who responded to induction treatment, including patients with aPL levels below the cut-off value for positivity, but remained stable in non-responding patients, in contrast to anti-dsDNA levels which decreased regardless of treatment outcomes

Summary

Introduction

Antiphospholipid antibodies (aPL) constitute a heterogeneous family of antibodies against phospholipids or phospholipid-binding proteins. They may occur in association with autoimmune diseases, transiently in association with infections, and sometimes in the general population. APS may appear as an isolated primary syndrome, or as a secondary condition to an underlying disease, systemic lupus erythematosus (SLE) being the most common [6]. Histological findings consistent with APLN were previously described as APS nephropathy (APSN) [7, 8], and studies have demonstrated that APSN may appear in a limited fraction of SLE patients without aPL [9, 10]

Methods

Results

Discussion

Conclusion