Donor-specific antibodies, immunoglobulin-free light chains, and BAFF levels in relation to risk of late-onset PTLD in liver recipients Journal Article

Authors: Engels, E. A.; Jennings, L. W.; Everly, M. J.; Landgren, O.; Murata, K.; Yanik, E. L.; Pfeiffer, R. M.; Onaca, N.; Klintmalm, G. B.
Article Title: Donor-specific antibodies, immunoglobulin-free light chains, and BAFF levels in relation to risk of late-onset PTLD in liver recipients
Abstract: 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.
Keywords: pathogenesis; impact; united-states; b-cell lymphoma; hla; posttransplant lymphoproliferative disorder; solid-organ transplantation
Journal Title: Transplantation Direct
Volume: 4
Issue: 6
ISSN: 2373-8731
Publisher: Lippincott Williams & Wilkins  
Date Published: 2018-06-01
Start Page: e353
Language: English
ACCESSION: WOS:000433903900003
DOI: 10.1097/txd.0000000000000792
PMCID: PMC6089512
PUBMED: 30123826
Notes: Article -- e353 -- Source: Wos
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MSK Authors
  1. Kazunori Murata
    12 Murata
  2. Carl Ola Landgren
    188 Landgren