Tumor Necrosis Factor Alpha Inhibitors as Immunomodulatory Antirejection Agents after Intestinal Transplantation

Abstract

We reported the successful administration of infliximab for late-onset OKT3-resistant rejection in two patients, who presented persistent ulcerative inflammation of the ileal graft after intestinal transplantation (ITX). Based on this experience, the present study demonstrated our long-term experience with infliximab for different types of rejection-related and inflammatory allograft alterations. Infliximab administration (5 mg/kg body weight (BW)) was initiated at a mean of 18.2 ± 14.1 months after transplantation. The number of administrations per patient averaged 8.4 ± 6.7. Repeat dosing was timed according to clinical signs and graft histology in addition to serum-levels of tumor necrosis factor alpha (TNFa ), lipopolysaccharide binding protein (LBP) and C-reactive protein (CRP). Infliximab was successful in the following patients: patients with late-onset OKT3-and steroid-refractory rejection who presented persistent ulcerative alterations of the ileal graft (n = 5), patients with ulcerative ileitis/anastomositis, who did not show typical histological rejection signs (n = 2), and one patient with early-onset OKT3-resistant rejection. Infliximab was not successful in one patient with earlyonset OKT3-resistant rejection that was accompanied by treatment-refractory humoral rejection. In conclusion, infliximab can expand therapeutic options for late-onset OKT3-and steroid-refractory rejection and chronic inflammatory graft alterations in intestinal allograft recipients.

Short-Term TNF-Alpha Inhibition Reduces Short-Term and Long-Term Inflammatory Changes Post-Ischemia/Reperfusion in Rat Intestinal Transplantation

“…The underlying mechanisms have been attributed to immunological processes similar to chronic inflammatory bowel disease, especially Crohn diseaseYassociated polymorphisms in the nucleotide-binding oligomerization domain containing 2 (NOD2) gene (3Y5). Our group has supported this hypothesis by successfully applying TNF> inhibitors like infliximab (6).…”

Clinical Allograft Rejection Syndromes in Intestinal Transplantation

“…For moderate and severe rejection, antilymphocyte agents such as thymoglobulin or alemtuzumab are used, for periods ranging from a few days up to 2-3 weeks, until clinical and histological resolution of the ACR episode. Additional therapies for resistant rejection include the use of antitumor necrosis factor monoclonal antibodies, such as infliximab [27]. In those episodes of rejection where a vascular component is present, and in which there is a suspicion of antibody-mediated rejection (often accompanied by an increase of DSA/PRA), several strategies to decrease humoral response are utilized.…”

Complications of Post-Transplant Immunosuppression

“…It is approved for treating the symptoms of rheumatoid arthritis. In transplantation it has been investigated in the treatment of severe rejection after intestinal transplantation [11]. Rituximab is a monoclonal antibody directed against the CD20 antigen on B cells.…”