Donor-specific Antibodies, Immunoglobulin-free Light Chains, and BAFF Levels in Relation to Risk of Late-onset PTLD in Liver Recipients

Autor: Eric A. Engels, MD, Linda W. Jennings, PhD, Matthew J. Everly, PharmD, Ola Landgren, MD, PhD, Kazunori Murata, PhD, Elizabeth L. Yanik, PhD, Ruth M. Pfeiffer, PhD, Nicholas Onaca, MD, Goran B. Klintmalm, MD, PhD
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Transplantation Direct, Vol 4, Iss 6, p e353 (2018)
Druh dokumentu: article
ISSN: 2373-8731
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DOI: 10.1097/TXD.0000000000000792
Popis: Background. Posttransplant lymphoproliferative disorder (PTLD) is a neoplastic complication of transplantation, with early cases largely due to immunosuppression and primary Epstein-Barr virus infection. Etiology may differ for later-onset cases, but the contributions of immunosuppression, immune reactivity to the donor organ, and chronic B cell activation are uncertain. Methods. We conducted a case-control study of late-onset PTLD (diagnosed >1 year posttransplant) in a cohort of liver recipients. We assessed serum samples (obtained >6 months before diagnosis in cases) from N = 60 cases and N = 166 matched controls for donor-specific antibodies (DSAs, evaluable for N = 221 subjects), immunoglobulin kappa and lambda free light chains (FLCs, N = 137), and B cell activating factor (BAFF, N = 226). Conditional or unconditional logistic regression was used to calculate adjusted odds ratios (aORs). Results. Circulating DSAs were less common in PTLD cases than controls (18% vs 30%), although this difference was borderline significant (aOR, 0.51; 95% confidence interval [CI], 0.24-1.10; P = 0.09). Donor-specific antibodies against class II HLA antigens predominated and likewise showed a borderline inverse association with PTLD (aOR, 0.58; 95% CI, 0.27-1.24). The FLC levels were less frequently abnormal in cases than controls, but measurements were available for only a subset and confidence intervals were wide (elevated kappa: aOR, 0.57; 95% CI, 0.15-2.12; P = 0.40; elevated lambda: aOR, 0.68; 95% CI, 0.30-1.50; P = 0.34). B cell–activating factor levels were not associated with PTLD. Conclusions. Our results suggest that circulating DSAs are associated with decreased risk of late-onset PTLD. Because DSAs may develop in the setting of underimmunosuppression, the inverse association with DSAs supports a role for immunosuppression in the etiology of late-onset PTLD.
Databáze: Directory of Open Access Journals