title: Pancreas allograft biopsies with positive c4d staining and anti-donor antibodies related to worse outcome for patients.
abstract: C4d+ antibody-mediated rejection following pancreas transplantation has not been well characterized. Therefore, we assessed the outcomes of 27 pancreas transplantation patients (28 biopsies), with both C4d staining and donor-specific antibodies (DSA) determined, from a cohort of 257 patients. The median follow-up was 50 (interquartile range [IQR] 8-118) months. Patients were categorized into 3 groups: group 1, patients with minimal or no C4d staining and no DSA (n = 13); group 2, patients with either DSA present but no C4d, diffuse C4d+ and no DSA or focal C4d+ and DSA (n = 6); group 3, patients with diffuse C4d+ staining and DSA (n = 9). Active septal inflammation, acinar inflammation and acinar cell injury/necrosis were significantly more abundant in group 3 than in group 2 (respective p-values: 0.009; 0.033; 0.025) and in group 1 (respective p-values: 0.034; 0.009; 0.002). The overall uncensored pancreas graft survival rate for groups 1, 2 and 3 were 53.3%, 66.7% and 34.6%, respectively (p = 0.044). In conclusion, recipients of pancreas transplants with no C4d or DSA had excellent long-term graft survival in comparison with patients with both C4d+ and DSA present. Hence, C4d should be used as an additional marker in combination with DSA in the evaluation of pancreas transplant biopsies.
authors.affiliation: Department of Pathology, Leiden University Medical Center, The Netherlands. H.de_Kort@lumc.nl
authors.forename: H
authors.initials: H
authors.lastname: de Kort
authors.forename: R B
authors.initials: RB
authors.lastname: Munivenkatappa
authors.forename: S P
authors.initials: SP
authors.lastname: Berger
authors.forename: M
authors.initials: M
authors.lastname: Eikmans
authors.forename: A
authors.initials: A
authors.lastname: van der Wal
authors.forename: E J
authors.initials: EJ
authors.lastname: de Koning
authors.forename: C
authors.initials: C
authors.lastname: van Kooten
authors.forename: E
authors.initials: E
authors.lastname: de Heer
authors.forename: R N
authors.initials: RN
authors.lastname: Barth
authors.forename: J A
authors.initials: JA
authors.lastname: Bruijn
authors.forename: B
authors.initials: B
authors.lastname: Philosophe
authors.forename: C B
authors.initials: CB
authors.lastname: Drachenberg
authors.forename: I M
authors.initials: IM
authors.lastname: Bajema
mesh_terms: D000328:Adult; D001706:Biopsy; D004396:Coloring Agents; D015935:Complement C4b / Q000032:analysis*; D057286:Electronic Health Records; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000276:immunology / Q000473:pathology*; D006680:HLA Antigens / Q000032:analysis; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation / Q000276:immunology / Q000473:pathology*; D010446:Peptide Fragments / Q000032:analysis*; D011183:Postoperative Complications / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D014184:Transplantation, Homologous / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D004396:Coloring Agents; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d