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Background
Despite data indicating a positive correlation between donor-speci
fic anti-HLA antibodies (DSAs) and early development o
f b
ronchiolitis obliterans synd
rome (BOS) in lung allogra
fts, the
role o
f an antibody-mediated p
rocess in acute and ch
ronic lung allogra
ft rejection has not been elucidated. In this study we evaluated pathologic
features o
f transplant lung biopsies in patients with and without DSAs.
Methods
Forty-one lung transplant biopsies from 41 patients at our institution were included in our study. The biopsy H&E slides were reviewed in a blinded fashion, and scored for presence of microvascular inflammation, acute rejection, bronchiolar inflammation and acute lung injury, as well as diffuse alveolar damage (DAD). Microvascular inflammation was graded by the presence of capillary neutrophils on a scale of 0 to 4+. For immunohistochemical analysis, the pattern and intensity of staining for C4d and C3d deposition were evaluated in airways and alveolar capillaries.
Results
Histopathology suspicious for antibody-mediated rejection (AMR)¡ªdefined as¡Ý2+ neutrophilic infiltration and/or DAD¡ªwere more common in DSA-positive cases than controls (11 of 16 vs 6 of 25, p<0.01). Evidence of allograft dysfunction was significantly more common among patients with both DSA and suspicious histopathology compared with controls (5 of 10 vs 3 of 25, p = 0.03). The combination of DSAs and histopathology suspicious for AMR was associated with both BOS (p = 0.002) and mortality (p = 0.03). Immunohistochemistry for C3d and C4d showed no correlation with each other, DSAs or histopathology.
Conclusions
Grade 2+ neutrophilic infiltration is the histopathologic finding most closely related to DSAs with graft dysfunction and development of BOS in lung transplant recipients and may be a marker for AMR.