Effectiveness of Bortezomib in a Patient With Acute Rejection Associated With an Elevation of Donor-Specific HLA Antibodies After Small-Bowel Transplantation: Case Report.
BACKGROUND
A significant association between donor-specific antibody (DSA) and graft rejection has recently been documented. However, confirmed strategy has not been established for DSA-associated rejection after intestinal transplantation (ITx).


METHODS
A 20-year-old male patient with chronic intestinal obstruction caused by hypoganglionosis of the entire intestine underwent cadaveric donor ITx with grafting performed on 232 cm of the small intestine, cecum, and a part of the ascending colon. On post-operative day (POD) 14, a histological evaluation showed an acute rejection of indeterminate grade. The patient had severe acute rejection on POD 16, which prompted us to administer bolus steroids and polyclonal anti-thymocyte antibody, along with baseline maintenance immunosuppression. The histopathological findings of the graft indicated typical acute cellular rejection, although C4d was positive. We then detected donor-specific HLA antibody. The patient initially responded well to the therapy and showed decreased histological rejection signs. However, the refractory low-grade rejection persisted in the graft. During this period, the patient showed increased levels of DSA, and we speculated that the persistent rejection was associated with DSA; thus, bortezomib was administered at this stage as a salvage therapy. This rejection was thereafter successfully controlled without severe adverse effect. Twenty-three months after ITx, the patient is currently alive with complete enteral autonomy.


CONCLUSIONS
A case of acute graft rejection followed by a marked elevation of DSA is presented. In this particular case, a modified treatment protocol using bortezomib in addition to the typical immunosuppressive agents was effective.
Department of Pediatric Surgery, Tohoku University School of Medicine, Sendai, Japan.
S
S
Fujiwara
Department of Pediatric Surgery, Tohoku University School of Medicine, Sendai, Japan. Electronic address: wada@ped-surg.med.tohoku.ac.jp.
M
M
Wada
Department of Pediatric Surgery, Tohoku University School of Medicine, Sendai, Japan.
H
H
Kudo
Department of Pediatric Surgery, Tohoku University School of Medicine, Sendai, Japan.
S
S
Yamaki
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
F
F
Fujishima
Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Japan.
K
K
Ishida
Department of Pediatric Surgery, Tohoku University School of Medicine, Sendai, Japan.
M
M
Nakamura
Department of Pediatric Surgery, Tohoku University School of Medicine, Sendai, Japan.
H
H
Sasaki
Department of Pediatric Surgery, Tohoku University School of Medicine, Sendai, Japan.
T
T
Kazama
Department of Pediatric Surgery, Tohoku University School of Medicine, Sendai, Japan.
H
H
Tanaka
Department of Pediatric Surgery, Tohoku University School of Medicine, Sendai, Japan.
M
M
Nio
D000208:Acute Disease; D000906:Antibodies / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000069286:Bortezomib / Q000627:therapeutic use*; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007421:Intestine, Small / Q000276:immunology / Q000637:transplantation*; D008297:Male; D014019:Tissue Donors; D055815:Young Adult
D000906:Antibodies; D000970:Antineoplastic Agents; D006680:HLA Antigens; D000069286:Bortezomib