Problems with diagnosis of antibody-mediated rejection

Transplant glomerulopathy

It is now clear that the Banff criteria for diagnosis of antibody-mediated rejection (AMR) which include 1) presence of donor specific antibody (DSA) 2) microvascular injury (MVI) such as glomerulitis 3) positive C4d , though specific, are not sensitive to detect AMR. Papadimitriou et al. study of surveillance and for cause allograft biopsies wants to verify whether any of the AMR characteristics can be used reliably to indicate this type of rejection. The main findings are:

• DSA alone was not predictive of higher risk of graft dysfunction.
• C4d staining alone was associated with the risk of graft dysfunction, especially in diffuse and focal pattern.
• Any type of MVI lesions (glomerulitis, peritubular capillaritis, transplant glomerulopathy) were associated with the risk of graft dysfunction. The risk increased with the increasing combined Banff score for these lesions.
• Of all MVI, transplant glomerulopathy seemed to be the most ominous sign. This is probably the reflection of chronic, persistent injury. However the study did not describe multilayering of peritubular capillary basement membrane which is the other chronic lesion. It is interesting to see whether this lesion is correlated with graft dysfunction.
• The peritubular capillaritis was detected before glomerulitis (21.8 vs. 32.4 months).
• The authors suggested the use of combined MVI scores as the basis of AMR diagnosis.
• The authors argued for change in terms "acute" and "chronic active" used by Banff schema because AMR occurs insidiously in patients without hypersensitization, the use of term acute seems inappropriate.