Antiphospholipid Antibodies in Lupus Nephritis

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.

ALCAM and VCAM-1 as urine biomarkers of activity and long-term renal outcome in systemic lupus erythematosus

“…Traditional markers such as anti-dsDNA, anti-C1q, hypocomplementaemia and albuminuria measured at the time of enrolment were not found to portend long-term renal function deterioration. Neither was aPL positivity found to have any impact, in conformity with a recent study that showed no association between the presence of aPL and long-term renal function impairment in patients with LN but without histological findings consistent with aPL-associated nephropathy, such as thrombotic microangiopathy [ 47 ]. In contrast, levels of U-sVCAM-1/creatinine were found to be a strong predictor of long-term renal function deterioration, with levels ≥75th percentile yielding a 23-fold increased risk of eGFR deterioration by ≥25% over a 10-year follow-up period.…”

Antiphospholipid Syndrome Nephropathy: From Pathogenesis to Treatment

“…Natejumnong et al showed that patients with SLE nephritis and LA positivity had higher systolic blood pressure (133.7 versus 121.9 mmHg, p = 0.005), serum creatinine (233.0 versus 94.9 μmol/L), and 24-h urine protein excretion (2.6 versus 1.4 g, p = 0.02), features associated with worse renal prognosis ( 6 ). However, in other lupus nephritis studies, aPL did not correlate with long-term kidney function ( 7 , 8 ) or even showed a protective effect against renal damage ( 9 ).…”

Regulatory effects of four ginsenoside monomers in humoral immunity of systemic lupus erythematosus

“…1), which was significantly inhibited in the presence of GS monomers except for GRg1 at the low dose, and this inhibitory effect was dose-dependent. As the secretion of autoantibodies and the incidence of SLE are closely linked (12), and the secretion of IgG and IgM has an important role in it (13,14), the concentration of IgG and IgM was measured by ELISA. The results demonstrated that the secretion of IgG and IgM was increased compared with that in the control group (Fig.…”