Antibody Mediated Rejection (AMR) in Lung Allografts: Pathologic Features in Patients with Clinically Diagnosed Humoral Rejection.
Jon H Ritter, Ramsey Hachem. Washington Univ Sch of Med, St. Louis, MO
Background: AMR is a newer concept in lung transplant pathology, and the features are less defined than for renal and cardiac allografts. We undertook this study to detail histologic features in cases with clinically diagnosed humoral lung allograft rejection.
Design: The clinical files of our institution were searched, for examples of “humoral rejection.” Selected cases met the NIH working definition of solid organ AMR, with allograft dysfunction, tissue pathology, complement deposition, and circulating donor antibodies. Cases were then reviewed for relevant histologic findings, including hemorrhage, necrosis, vasculitis/capillaritis, interstitial neutrophils, acute and organizing lung injury, and cellular rejection. Immunostains for complement were also reviewed.
Results: Eighteen cases fit the clinical definition for AMR. The time from transplant to the index biopsy for the AMR diagnosis ranged from 1 to 120 weeks (mean 40 weeks). All patients had allograft dysfunction, and 17/18 had antibodies (14/18 with circulating donor-specific antibodies; 3/18 with anti-HLA antibodies only) Fourteen patients had C4d immunodeposition in the lung, 2 cases had equivocal staining, and 2 cases were not tested. Acute interstitial pneumonitis with neutrophils was the most common histologic feature, seen in 13/18 cases; the second most common finding was organizing pneumonia/BOOP (11/18). Vasculitis/capillaritis was seen in 8/18 cases, with extensive hemorrhage in 5/18, and alveolar necrosis in 3/18. Four cases showed concomitant acute cellular rejection, including 2 cases each of A1 and A2. The 14 cases with positive C4d staining ranged from strong diffuse capillary staining, to more focal endothelial staining, sometimes in larger vessels only. Two equivocal cases showed only C4d deposits in the interstitium, or in areas of fibrin exudate. There was high background elastic tissue staining complicating interpretation in most cases.
Conclusions: AMR is an important process in the lung transplant setting, and may occur well outside of the early post-transplant setting. The most common finding is acute interstitial pneumonitis, followed by organizing injury patterns; fewer cases show classic features of vasculitis or related lesions. The significance of C4d immunostains, and the delineation of patterns to be considered positive remains a point for further study. AMR should be in the differential diagnosis when there is lung injury without clear-cut infection or other etiology.
Tuesday, March 1, 2011 2:15 PM
Platform Session: Section F, Tuesday Afternoon