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A recent study of pediatric lupus nephritis disease activity and severity in pediatric-onset systemic lupus erythematosus patients found that renal C4d shows promise as a biomarker for renal disease in this patient population.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple systems. While SLE can manifest at any age, a notable percentage of cases, approximately 15%–20%, initiate during childhood. 

Pediatric-onset SLE patients exhibit a more aggressive disease course compared to those with adult-onset, often complicated by lupus nephritis (LN), which affects an estimated 50%–82% of pediatric SLE patients. Diagnosis and severity of LN are essential as kidney involvement often determines treatment options. 

In the search for a diagnostic biomarker for pediatric LN, C4d has emerged as a potential candidate. 

This study explores renal C4d deposition in pediatric LN patients, assessing its diagnostic significance and potential as a disease activity indicator with the ultimate goal of improved understanding and management of pediatric-onset SLE with LN.

C4d’s presence has been associated with antibody-mediated tissue damage in various diseases, including renal allograft rejection, having been identified along peritubular capillaries (PTCs) and introduced into clinical practice in the late 1990s. 

Methods, Analysis, and Assessments 

In the study, a retrospective analysis was performed involving 58 pediatric lupus nephritis (LN) patients to evaluate the diagnostic potential of renal C4d staining. C4d staining on renal biopsy samples was detected using immunohistochemistry. 

Subsequently, an assessment was conducted on the clinical and laboratory data available at the time of kidney biopsy. Also, an evaluation of renal disease activity based on histological injury was carried out, with categorization determined by the status of C4d staining.

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A Brief Overview 

Glomerular C4d (G-C4d) staining was detected in all 58 cases of LN. 

Patients with a G-C4d score of 2 had more severe proteinuria than those with a G-C4d score of 1 (24-h urinary protein: 3.40 ± 3.55 g vs. 1.36 ± 1.24 g, P < 0.05). 

Peritubular capillary C4d (PTC-C4d) was found in 34 of 58 LN patients (58.62%). The PTC-C4d-positive patient groups (PTC-C4d score of 1 or 2) showed higher serum creatinine and blood urea nitrogen levels, along with greater renal pathological activity index (AI) and SLE disease activity index (SLEDAI) scores. They had lower serum complement C3 and C4 levels compared to PTC-C4d-negative patients (P < 0.05). 

It was further noted that 11 of 58 LN patients (18.96%) displayed positive tubular basement membrane C4d (TBM-C4d) staining. A higher proportion of TBM-C4d-positive patients than TBM-C4d-negative patients (63.63% vs. 21.27%) had hypertension.

The Study’s Findings 

The findings of the study demonstrate positive correlations between glomerular C4d (G-C4d), peritubular capillary C4d (PTC-C4d), and tubular basement membrane C4d (TBM-C4d) with proteinuria, disease activity and severity, and hypertension, respectively, among pediatric LN patients. 

These results suggest the potential of renal C4d as a biomarker for gauging disease dynamics and severity in this patient group. 

The observed correlations from the study offer insights into the development of innovative diagnostic and therapeutic strategies tailored to pediatric-onset SLE with LN.


Wang, X., Fu, S., Yu, J., Tang, D., Wu, H., & Xu, Z. (2023). Renal C4d is a potential biomarker of disease activity and severity in pediatric lupus nephritis patients. Frontiers in Pediatrics, 11. https://doi.org/10.3389/fped.2023.1193917