Five-year histological and serological follow-up of operationally tolerant pediatric liver transplant recipients enrolled in WISP-R.
Pediatric liver transplant recipients arguably have the most to gain and the most to lose from discontinuing immunosuppression (IS). Whereas IS undoubtedly exerts a cumulative toll, there is concern that insufficient or no IS may contribute to allograft deterioration. Twelve pediatric recipients of parental living donor liver grafts, identified as operationally tolerant through complete IS withdrawal (WISP-R; NCT00320606), were followed for a total of 5 years (1 year of IS withdrawal and 4 years off IS) with serial liver tests and autoantibody and alloantibody assessments. Liver biopsies were performed 2 and 4 years off IS, and, at these time points, immunoglobulin G (IgG) subclass and C1q binding activity for donor-specific antibodies (DSAs) were determined. There were no cases of chronic rejection, graft loss, or death. Allografts did not exhibit progressive increase in inflammation or fibrosis. Smooth-muscle actin expression by stellate cells and CD34 expression by liver sinusoidal endothelial cells remained stable, consistent with the absence of progressive graft injury. Three subjects never exhibited DSA. However, 3 subjects showed intermittent de novo class I DSA, 4 subjects showed persistent de novo class II DSA, and 5 subjects showed persistent preexisting class II DSA. Class II DSA was predominantly against donor DQ antigens, often of high mean fluorescence intensity, rarely of the IgG3 subclass, and often capable of binding C1q.



Operationally tolerant pediatric liver transplant recipients maintain generally stable allograft histology in spite of apparently active humoral allo-immune responses. The absence of increased inflammation or progressive fibrosis suggests that a subset of liver allografts seem resistant to the chronic injury that is characteristic of antibody-mediated damage. (Hepatology 2017;65:647-660).
Department of Surgery, University of California San Francisco, San Francisco, CA.
Sandy
S
Feng
Department of Pathology, University of Pittsburgh, Pittsburgh, PA.
Anthony J
AJ
Demetris
Rho, Chapel Hill, NC.
Katharine M
KM
Spain
Immune Tolerance Network, Bethesda, MD.
Sai
S
Kanaparthi
Immune Tolerance Network, Bethesda, MD.
Bryna E
BE
Burrell
Department of Pediatrics, Yale School of Medicine, New Haven, CT.
Udeme D
UD
Ekong
Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL.
Estella M
EM
Alonso
Department of Surgery, University of California San Francisco, San Francisco, CA.|Department of Pediatrics, University of California San Francisco, San Francisco, CA.
Philip
P
Rosenthal
Immune Tolerance Network, Bethesda, MD.
Laurence A
LA
Turka
Rho, Chapel Hill, NC.
David
D
Ikle
Immune Tolerance Network, Bethesda, MD.
Nadia K
NK
Tchao
D064591:Allografts; D001707:Biopsy, Needle; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007518:Isoantibodies / Q000276:immunology; D008107:Liver Diseases / Q000151:congenital* / Q000473:pathology / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D019520:Living Donors; D008297:Male; D011446:Prospective Studies; D018570:Risk Assessment; D013997:Time Factors; D014181:Transplantation Immunology; D016896:Treatment Outcome
D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007518:Isoantibodies