C4d detection and histological patterns in the diagnosis of antibody‐mediated rejection after lung transplantation: a single‐centre study

Abstract

Aims

Antibody‐mediated rejection (AMR) is an emerging and challenging issue in transplantation. Endothelial deposition of C4d and microvascular inflammation (MI) are reliable markers of AMR in renal and cardiac transplantation (Tx), but remain controversial in lung.

Methods and results

In order to assess C4d immunohistochemistry and histological patterns for the diagnosis of lung AMR, we reviewed 158 transbronchial biopsies (TBBs) (n=85 clinically indicated, and n=73 surveillance TBBs) from 48 recipients, blindly of clinical and serological data. C4d was scored as 0, 1+ (<10%), 2+ (10% to 50%) or 3+ (>50%). TBBs were reassessed for MI and acute lung injury (ALI). Donor‐specific antibodies (DSAs), acute and chronic graft dysfunction (CLAD) were recorded.

C4d3+, C4d2+, C4d1+ and C4d0 occurred respectively in 4 (2.5%), 6 (3.8%), 28 (17.7%) and 120 (75.9%) TBBs. MI and ALI were rare but more frequent in C4d1‐3+ TBBs than in the absence of C4d.C4d2+ was frequently observed with concomitant infection. Among the surveillance TBBs, only 2 (2.7%) displayed MI. Neither ALI nor C4d3+ was diagnosed on surveillance TBBs. No significant association was found between histopathological findings and DSAs. All 4 patients with C4d3+ could retrospectively be diagnosed with AMR and developed CLAD.

Conclusion

Although rare, diffuse C4d deposition appears as a strong argument for acute clinical AMR in lung transplantation, whereas intermediate C4d2+ requires more investigations. In stable patients, histopathology and C4d may lack sensitivity to diagnose sub‐clinical AMR. This emphasizes the need of a multidisciplinary evaluation of each suspected AMR case, and of complementary diagnostic tools.

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