Humoral (antibody-mediated) rejection after intestinal transplantation in children : a poor prognostic factor
Florence Lacaille1, Laetitia-Marie Petit1, Marion Rabant2, Caroline Suberbielle3, Danielle Canioni2, Christophe Chardot4, Olivier Goulet1
1Pediatric Hepatogastroenterology-Nutrition, HÃ´pital Necker-Enfants malades, Paris, France; 2Pathology, HÃ´pital Necker-Enfants malades, Paris, France; 3Immunology, HÃ´pital Saint-Louis, Paris, France; 4Pediatric Surgery, HÃ´pital Necker-Enfants malades, Paris, France
Humoral or antibody-mediated rejection (AMR), well described after kidney transplantation (Tx), is probably responsible for severe steroid-resistant rejection and early graft loss after intestinal transplantation (ITx). The diagnosis and treatment are however unclear. We report here our experience in a group of children, and suggest to validate a scoring system, in order to trigger an early adequate reaction to this severe complication.
Patients and methods. From 06/2008 to 07/2012, 28 children were on the waiting list, 19 received an ITx : 11 isolated small bowel (SBTx), 4 combined liver-small bowel (L-SBTx) including 2 re-Tx, 2 multivisceral (MVTx, 1 with kidneys), 1 modified multivisceral (MMVTx). Median age at Tx was 7 years (1.5-19). In 16/28, pre-Tx screening for anti-HLA antibodies was performed with Luminex (scoring in MFI), and in all of them post-Tx. Immunosuppression was tacrolimus, methylprednisolone and basiliximab. AMR was suspected on presence of donor-specific anti-HLA antibodies (DSA) over 1000 MFI, or vascular lesions or positive C4d staining on biopsies.
Results. In 3/19 patients, no DSA were ever found and they are alive and well. In 3/19 early graft loss or death was due to surgical complications. Six patients had pre-Tx DSA (2 re-Tx). Post-Tx, 13/19 had DSA over 1000 MFI (68%), 7 SBTx, 4 L-SBTx, and 2 MVTx. In 6/13 patients, positivity of DSA was contemporaneous of severe clinical and histological rejection, in 3 with early positive C4d staining. In 7/13, the biopsies showed a mild acute rejection (2/7) or were normal (5/7). They received methylprednisolone, IV immunoglobulins (only treatment in 2 with normal biopsies) and plasmapheresis, and rescue treatment with infliximab (1/6), rituximab (2/6) and eculizimab (1/6). Three children died early on, the graft was removed in one, 2 were weaned off PN. Two children died 10 and 12 months post-Tx, of GVH and of severe rejection on poor compliance. 7/8 surviving patients are weaned off PN with a normal graft function, and a median follow-up of 18 months.
Discussion. AMR is a poor prognostic factor after ITx. The treatment aims at urgently removing or neutralizing the DSA. A scoring system including the clinical findings, typical pathological lesions and the DSA MFI score should be prospectively validated, in order to early diagnose and treat AMR, and improve the prognosis. The role of DSA in late graft loss will also need further studies.