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Do Commonly Evaluated Histological Finings in Bronchial Biopsies Correlate with De Novo DSA after Lung Transplantation?

M. Askar, P. Reville, L. Klingman, J. Schold, J. Daghstani, M. Budev, K. McCurry, C. Farver

Allogen Laboratories, Cleveland Clinic, Cleveland, OH
Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH
University of Toledo, Toledo, OH
Pulmonary, Allergy and Critical Care Medicine, Cleveland Clinic, Cleveland, OH
Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH
Anatomic Pathology, Cleveland Clinic, Cleveland, OH

Meeting: 2013 American Transplant Congress

Abstract number: A637

The de novo development of donor HLA specific antibodies (DSA) after lung transplantation has been implicated in acute and chronic rejection. However, the existence of antibody mediated rejection (AMR) in lung allografts remains a matter of debate. In addition, the association between DSA and histological findings on lung biopsies is unclear and thus this study was undertaken to investigate this association.

We retrospectively analyzed the records of 85 lung transplant recipients who had for-cause post-transplant monitoring for DSA within ±1 week of the a biopsy date (paired biopsies). Some patients had multiple paired biopsies (n=116). All recipients had protocol bronchial biopsies at 2 weeks, 1, 3, and 6 months, at 1 year and for cause thereafter. We attempted to correlate de novo DSA with the following histological findings: C4d staining, acute rejection ≥ISHLT grade 2A, acute lung injury (ALI) and organizing pneumonia (OP).

25 patients developed de novo DSA (29%), of those 4 had HLA class I DSA, 18 had class II, and 3 had both class I and II. The average post-transplant day for detection of class I DSA was 166 and 296 for class II. The distribution of histological findings in patients with and without DSA is shown in table 1.

  C4d+ Acute Rejection ≥ A2 ALI OP
All Biopsies (n=116) 5 (4%) 20 (17%) 41 (35%) 8 (7%)
DSA Biopsies (n=62) 5 (8%) 16 (26%) 23 (37%) 5 (8%)
No DSA Biopsies (n=54) 0 (0%) 4 (7%) 18 (33%) 3 (6%)
p-value 0.060 0.013 0.701 0.722
Specificity/Sensitivity 0.49/1.00 0.52/0.80 0.48/0.56 0.47/0.63
PPV/NPV 0.08/1.00 0.26/0.93 0.37/0.67 0.08/0.94

We did not observe an appreciable difference in the mean graft survival among patients with and without DSA (600 vs. 606, respectively).

Conclusion: Although some of the commonly evaluated histological changes seemed to correlate significantly with de novo DSA, none of them showed sufficient specificity to have a significant positive predictive value. More histological features need to be evaluated individually or in combinations to guide the histological diagnosis of AMR.

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To cite this abstract in AMA style:

Askar M, Reville P, Klingman L, Schold J, Daghstani J, Budev M, McCurry K, Farver C. Do Commonly Evaluated Histological Finings in Bronchial Biopsies Correlate with De Novo DSA after Lung Transplantation? [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/do-commonly-evaluated-histological-finings-in-bronchial-biopsies-correlate-with-de-novo-dsa-after-lung-transplantation/. Accessed May 14, 2025.

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