Antiphospholipid antibody profiles in lupus nephritis with glomerular microthrombosis: a prospective study of 124 cases

Abstract

Introduction Glomerular microthrombosis (GMT) is a common vascular change in patients with lupus nephritis (LN). The mechanism underlying GMT is largely unknown. Although several studies have reported the association of antiphospholipid antibodies (aPL) with GMT, the relation between GMT and aPL remains controversial. Previous studies have demonstrated that some aPL could bind to several hemostatic and fibrinolytic proteases that share homologous enzymatic domains. Of the protease-reactive aPL, some can inhibit the anticoagulant activity of activated protein C and the fibrinolytic function of plasmin, and hinder the antithrombin inactivation of thrombin. The purpose of this study was to investigate the prevalence of GMT in LN patients and examine the relation between the aPL profiles (including some proteasereactive aPL) and GMT.

Association between antiphospholipid antibodies and factor Bb in lupus nephritis patients with glomerular microthrombosis

“…In this retrospective study, the presence of GMT was 24.7%, which is consistent with previous studies . In addition, we also found that LN patients with GMT had more active and severe kidney disease than those without GMT, as evidenced by a higher SLEDIA, a higher activity index, more class IV LN, more active hematuria and proteinuria, and elevated levels of serum creatinine, which is also similar to the findings of previous studies …”

“…GMT may be an important cause of renal injury and renal dysfunction in a subset of patients with LN, but the mechanisms underlying GMT in patients with LN remain obscure. To understand what factors confer the risk of GMT in LN, many previous studies examined the association of GMT with aPLs in patients with LN . However, the conclusions were highly controversial.…”

“…The following data were obtained: classification, activity index and chronicity index. The intensity of glomerular immunofluorescence staining for IgG, IgM, IgA, C3, C4, C1q and Bb was semi‐quantitatively scored on a scale of 0‐3, where 0 = no glomerular staining, 1 = mild glomerular staining, 2 = moderate glomerular staining, and 3 = intense glomerular staining . IgG, IgM, IgA, C3 and C4 were stained by direct immunofluorescence; Bb was stained by indirect immunofluorescence, briefly, mouse anti‐human Bb antibody (Quidel Corporation) was used as primary antibody, and fluorescein isothiocyanate (FITC)‐labeled goat anti‐mouse IgG (Zhongshan Golden Bridge Biotechnology) was used as secondary antibody.…”

“…The presence of aPLs has been closely related to the development of thrombosis and pregnancy complications in antiphospholipid syndrome (APS). GMT has also been associated with aPLs in patients with LN in some studies, but the mechanism of aPL‐induced GMT is still a topic of controversy.…”

Diverse vascular lesions in systemic lupus erythematosus and clinical implications

“…Recently, several studies have suggested that IgA antib2 glycoprotein I (b2GPI) is the most prevalent isotype in SLE, with a significant association with thrombotic events [34] and an increased prevalence of morbidities involving organs of mucosal immunity [35]. Zheng et al [36] found that the lupus anticoagulant and antibodies against b2GPI and thrombin might play a role in glomerular microthrombosis. SLE patients with these factors had more severe renal tissue injuries and poorer renal function than those without them.…”