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Clinical Relevance of Arteriolar C4d Staining in Patients With Chronic-active Antibody-mediated Rejection: A Pilot
Malou L H Snijders1, Kasia A Sablik2, Thierry P P van den Bosch1
1Rotterdam Transplant Group, Department of Pathology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
Insights
Arteriolar C4d staining is more frequent in chronic-active antibody-mediated rejection (c-aAMR) and linked to better kidney transplant outcomes. This finding suggests arteriolar C4d may indicate a specific injury pattern in c-aAMR.
Area of Science:
- Nephrology
- Immunology
- Transplantation
Background:
- C4d staining in peritubular capillaries is a known marker for antibody-mediated rejection (AMR).
- The significance of C4d deposition outside of peritubular capillaries, specifically in arterioles, remains unclear.
- This study focuses on the role of arteriolar C4d staining in chronic-active AMR (c-aAMR).
Purpose of the Study:
- To investigate the significance and diagnostic value of arteriolar C4d staining in kidney allografts with chronic-active antibody-mediated rejection (c-aAMR).
- To determine the association between arteriolar C4d deposition and histological features like arteriolar hyalinosis.
- To evaluate the impact of arteriolar C4d staining on long-term kidney allograft survival.
Main Methods:
- Analysis of for-cause renal allograft biopsies diagnosed with c-aAMR (Banff Classification 2015).
- Comparison with a matched control group of renal allograft biopsies and native renal biopsies.
- Semi-quantitative scoring of arteriolar C4d staining (0 to 3+).
Main Results:
- Arteriolar C4d staining was present in 85% of c-aAMR cases, significantly more than in matched controls (P = 0.01).
- A trend towards significance was observed when comparing c-aAMR cases with native renal biopsies (P = 0.05).
- Arteriolar C4d staining correlated with arteriolar hyalinosis (P = 0.004), and a score of ≥2 was independently associated with better graft outcome (HR, 0.260; P = 0.004).
Conclusions:
- Arteriolar C4d staining is more prevalent in c-aAMR biopsies compared to controls.
- The presence and extent of arteriolar C4d staining are associated with specific histological changes and improved graft outcomes.
- Larger studies are warranted to confirm these findings and elucidate the precise role of arteriolar C4d in antibody-mediated injury.
Background:
C4d staining in peritubular capillaries is a well-established feature of antibody-mediated rejection (AMR). The relevance of C4d staining outside peritubular capillaries is not well understood. We investigated the significance of arteriolar C4d staining in chronic-active AMR (c-aAMR).
Methods:
All for-cause renal allograft biopsies performed in 2007-2014 at the Erasmus MC and meeting the criteria for suspicious/diagnostic c-aAMR using the Banff Classification 2015 were included. For comparison, renal allograft biopsies from a matched control group and native renal biopsies were analyzed. Arteriolar C4d staining was semiquantitatively scored as negative (0), small deposits in 1 arteriole (1+), small/large deposits in >1 arterioles (2+), or at least extensive deposits in most arterioles (3+).
Results:
Thirty-four of 40 (85%) patients with c-aAMR showed arteriolar C4d staining. A significant difference in arteriolar C4d score was observed between cases and matched controls (P = 0.01) and a trend toward significance difference between cases and native renal biopsies (P = 0.05). In the cases, arteriolar C4d staining was significantly associated with severity of arteriolar hyalinosis (P = 0.004) and ≥2 arteriolar C4d staining was independently associated with better graft outcome in a multivariate Cox regression analysis (hazard ratio, 0.260; 95% CI, 0.104-0.650; P = 0.004).
Conclusions:
This pilot study shows that arteriolar C4d staining is more common in biopsies with c-aAMR compared with those without and that it is associated with arteriolar hyalinosis and ≥2 arteriolar C4d staining is associated with superior graft outcome. However, larger studies are needed to examine these findings in more detail to asses if arteriolar C4d staining is truly related to antibody-mediated injury.
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