Glomerular inflammation in renal allografts biopsies after the first year: cell types and relationship with antibody-mediated rejection and graft outcome.
BACKGROUND
Antibody-mediated rejection manifests with glomerular and peritubular capillary inflammation and transplant glomerulopathy (TG). The role of glomerular inflammation (GI) components in the development of TG and their impact on outcome are incompletely understood.


METHODS
GI was quantified on hematoxylin-eosin, CD3, CD20, and CD68 stains on biopsies from 240 patients with grafts functioning more than or equal to 1 year.


RESULTS
A predominance of CD68+ cells followed by less numerous CD3+ cells was found in TG and glomerulitis. CD68+ cells more than 12 in the most inflamed glomerulus were strongly associated with TG, donor-specific antibody (DSA), and C4d staining. Glomerular CD68+ cells correlated with peritubular capillary multilamellation, and similarly, the Banff g score correlated with light and electron microscopic indexes of chronic microvascular damage. Overall, GI components correlated with the g score, DSA, and peritubular capillary C4d+. The Banff cg 1, 2, and 3 scores showed high levels of GI composed mostly of CD68+ cells, similar to but not higher than cases of g2 and g3 glomerulitis. Glomerular T cells and neutrophils followed similar trends as the predominant macrophages. T-cell-mediated rejection in this cohort did not significantly affect the composition of GI. Prognostically, all types of pronounced GI, g scores, DSA+, C4d+, and capillaropathy were associated with worse prognosis; however, only high level of macrophages was an independent predictor of graft failure.


CONCLUSIONS
GI in more than or equal to 1 year grafts is mostly antibody-mediated rejection related, correlates with chronic microvascular damage, and consists predominantly of macrophages. The latter seem to represent a pivotal pathogenetic, diagnostic, and prognostic factor in this setting.
Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA. jpapa001@umaryland.edu
John C
JC
Papadimitriou
Cinthia B
CB
Drachenberg
Raghava
R
Munivenkatappa
Emilio
E
Ramos
Joseph
J
Nogueira
Charles
C
Sailey
David K
DK
Klassen
Abdolreza
A
Haririan
D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001706:Biopsy; D002196:Capillaries / Q000473:pathology; D015935:Complement C4b / Q000032:analysis; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000473:pathology*; D006085:Graft Survival; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D007518:Isoantibodies / Q000276:immunology; D007678:Kidney Glomerulus / Q000473:pathology*; D016030:Kidney Transplantation / Q000473:pathology*; D007684:Kidney Tubules / Q000098:blood supply; D008833:Microcirculation / Q000502:physiology; D010446:Peptide Fragments / Q000032:analysis; D018570:Risk Assessment; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000473:pathology; D017211:Treatment Failure; D016896:Treatment Outcome; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015935:Complement C4b; D007518:Isoantibodies; D010446:Peptide Fragments; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C032261:complement C4d