Parodis Ioannis, Arnaud Laurent, Gerhardsson Jakob, Zickert Agneta, Sundelin Birgitta, Malmström Vivianne, Svenungsson Elisabet, Gunnarsson Iva
Department of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
PLoS One. 2016 Jun 23;11(6):e0158076. doi: 10.1371/journal.pone.0158076. eCollection 2016.
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.
狼疮性肾炎（LN）是系统性红斑狼疮（SLE）的主要表现形式。抗磷脂抗体（aPL）是否会改变LN的病程仍不清楚。因此，我们研究了aPL对LN患者短期和长期肾脏结局的影响。我们对诊断为LN（n = 204）或未诊断为LN（n = 294）的SLE患者进行了aPL水平的横断面评估，并对64例经活检证实为活动性LN的患者（52例增殖性、12例膜性）在诱导治疗前后进行了前瞻性评估（短期结局）。在前瞻性LN队列中，经过中位11.3年（范围：3.3 - 18.8年）的随访后，通过估计肾小球滤过率（eGFR）和慢性肾脏病（CKD）分期来确定长期肾脏结局。横断面分析显示，LN与IgG/IgM抗心磷脂或抗β2糖蛋白I抗体或狼疮抗凝物之间无关联。活动性LN患者和非肾脏SLE患者的aPL阳性率和水平相似。在LN诱导治疗后，有反应者的血清IgG/IgM aPL水平下降（所有均p<0.005），但无反应者未下降。在活动性LN期和治疗后，与无IgG aPL患者相比，有IgG而非IgM aPL的患者肌酐水平更高。无论是aPL阳性率还是水平，在长期随访中均与基线或治疗后eGFR的变化无关。此外，在最后随访时CKD分期≥3期与1 - 2期的患者中，基线和治疗后的aPL阳性率和水平相似。总之，未发现aPL阳性率和水平与SLE患者LN的发生有关。然而，LN患者中IgG aPL阳性与肾功能短期损害有关，而未观察到对长期肾脏结局有影响。此外，诱导治疗后仅在有反应者中IgG和IgM aPL水平下降，表明aPL水平受免疫抑制药物的影响具有反应依赖性。
