Lupus With Antiphospholipid Antibodies Associated Nephropathy Clinicopathological Study And β ₂ Glycoprotein I Role

BackgroundAntiphospholipid syndrome (APS) is defined by thrombosis or fetal loss in the presence of Antiphospholipid antibodies (aPL). APS nephropathy presents as a group of small vessel vaso-occlusive lesions in histopathology. These include thrombotic microangiopathy (TMA), fibrous intimal hyperplasia (FIH), fibrous occlusion, organized thrombi and focal cortical atrophy (FCA). However, similar histological presentations can also be found in aPL positive patients especially in SLE patients without the clinical presentation of APS. In the revised criteria consensus statement for APS, the presence of a positive aPL along with the pathological kidney findings including TMA, FIH, FCA and Tubular thyroidization is defined as aPL-associated nephropathy (APLN). Few researches have focused on clinical and pathological features of SLE with APLN so far.As a major antigen recognized by aPL, β2glycoprotein Ⅰ (β2GPI) plays a critical role in the thrombosis caused by aPL.At this point, the diagnosis of APLN is only depending on the pathological changes. There are no specific markers for APLN.ObjectiveTo evaluate the clinical features, and outcome of SLE with APLN. To establish the possible diagnostic value of β2GPI in predicting APLN.Methods(1) Data of229cases of SLE patients admitted to Peking Union Medical College Hospital was reviewed. Kidney biopsy was performed on all of these patients.87patients had the histopathological changes of APLN. We retrospectively analyzed the clinical manifestations and renal survival of those patients.(2) Using retrospective analysis, we compared the difference in clinical features and outcomes between SLE patients with APLN and without APLN.(3) In46SLE with APLN patients,17SLE without APLN patients and14non-SLE patients, we investigated the deposit of β2GPI in the endothelium of kidney vessels using immunohistochemistry.Results(1) The histopathological changes of APLN were found in66.7%of patients with aPL, compared to only28.4%of patients without aPL. The histopathological lesions of APLN were strongly associated with Anti-cardiolipin antibody (aCL), Lupus anticoagulant (LA) as well as antiβ2GPI antibody. SLE patients with the histopathologic changes of APLN had higher creatinine levels.Also a higher death/ESRD ratio was found in this group of patients.(2) The prominent clinical manifestations of SLE with APLN patients included hypertension (59.2%) and renal insufficiency (26.6%).The kidney prognosis in SLE with APLN was worse than in SLE with APLN.(3) We found β2GPI deposits in kidney arterioles in17.4%of SLE with APLN patients. No β2GPI deposits were found in the SLE without APLN group and the nonSLE group. The deposits in capillary endothelium were found in32.6%of SLE with APLN patients. The incidence of the deposits in these patients was significantly higher than that of the SLE without APLN and the nonSLE group.Conclusions1. Among SLE patients, APLN is related to the existence of aPL and contributes to higher serum creatinine levels and poor prognosis.2. Deposits of β2GPI could be a specific marker for SLE with APLN. But further studies are needed.