Abstract
ObjectivesThis study aimed to determine the prevalence and localization of complement factor C4d in renal biopsies from patients with lupus nephritis (LN), as well as its associations with the disease’s clinico-pathological features. The correlation between arteriolar C4d deposition and renal microvascular lesions (RVLs) was further analyzed.MethodsA total of 325 biopsy-proven LN patients were enrolled, and their clinico-pathological data were collected. C4d staining of renal biopsies was performed by immunohistochemistry. The associations between C4d deposition and the clinico-pathological features were further analyzed.ResultsC4d deposition was present in most (98.8%) renal specimens in our cohort. These deposits were localized in the glomeruli (98.2%), tubular basement membrane (TBM) (43.7%), arterioles (31.4%), and peritubular capillary (33.8%). Patients with TBM C4d staining had higher disease activity (measured with the Systemic Lupus Erythematous Disease Activity Index) and higher National Institutes of Health pathological activity and chronicity indices (all P < 0.01). Patients with arteriolar C4d deposition were more likely to develop RVLs (91.2%) compared to those with no arteriolar C4d deposition (78.0%; P = 0.004), especially with two or more types of RVLs (P < 0.001). During the mean follow-up of 55.8 months, arteriolar C4d was related to worse renal outcomes [hazard ration (HR): 2.074, 95% confidence interval (CI) 1.056–4.075, P = 0.034]. Multivariate Cox hazard analysis showed that co-deposition of arteriolar C4d and C3c was an independent risk factor (HR: 3.681, 95% CI 1.519–8.921, P = 0.004) for predicting renal outcomes.ConclusionsC4d deposition was common in renal tissues from LN patients. TBM C4d deposition was related to the disease activity, and arteriolar C4d deposition was associated with RVLs and worse renal outcomes.
Highlights
Systemic lupus erythematous (SLE) is an autoimmune disease with a wide variety of clinical manifestations and serological abnormalities [1]
ANA, antinuclear antibody; Anti-dsDNA Ab, Anti-double-stranded DNA antibody; aCL, anti-cardiolipin antibody; Systemic Lupus Erythematous Disease Activity Index (SLEDAI), systemic lupus erythematosus disease activity index; activity indices (AIs), activity index; chronicity indices (CIs), chronicity index; ICD, immune complex deposits; AS, atherosclerosis; TMA, thrombotic microangiopathy; NNV, noninflammatory necrotizing vasculopathy; TRV, true renal vasculitis; n, number; s.d., standard deviation; IQR, interquartile range.*C4 was analyzed based on the data of 239 patients with C4 level tested at the onset of the disease; #aCL was analyzed based on the data of 198 patients with aCL level tested at the onset of the disease
Three patients died of heart failure and one patient died of severe infection
Summary
Systemic lupus erythematous (SLE) is an autoimmune disease with a wide variety of clinical manifestations and serological abnormalities [1]. Lupus nephritis (LN) presents in up to 60% of patients during the disease course [2] and contributes to SLE’s morbidity and mortality. Renal histopathology is closely related with its clinical characteristics, responses to treatment, and patient prognosis [3]. Complement activation plays a key role in LN pathogenesis [4]. The classical pathway is thought to be the dominant pathway for complement activation in LN, which is triggered by the interaction of C1q with immune complexes [5]. Several studies detected mannose-binding lectin (MBL) in the glomeruli of LN patients [6, 7], implicating its participation in disease progression
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