C4d is a good marker of acute humoral rejection in small bowel transplantation
Marion RABANT1, Laetitia-marie PETIT1,2, Nicole BROUSSE1, Caroline SUBERBIELLE4, Jean Paul DUONG VAN HUYEN1, Jacques patrick BARBET1, Olivier GOULET2, Christophe CHARDOT3, Florence LACAILLE2, Danielle CANIONI1
1Pathology, Necker Hospital, Paris, France; 1SURGERY, UNIVERSITY OF SÃƒO PAULO, Santana de ParnaÃba- SP, No, Brazil; 2Pediatric Gastrology and Hepatology, Necker Hospital, Paris, France; 3Pediatric Surgery, Necker hospital, Paris, France; 4Immunology and histocompatibility department, Saint Louis Hospital, paris, France
Background. Diagnosis criteria for acute humoral rejection are well established in kidney and heart transplantation, while no consensus exists for small bowel (SB) transplantation rejection.
Methods. We retrospectively studied intestinal biopsies, obtained from pediatrics SB allograft recipients (May 2009 to August 2011), with (n=13) and without (n=3) Donor Specific Antibodies (DSA). We systematically looked for histological signs for cellular rejection, vascular changes (microcirculation inflammation, thrombosis, arteritis), edema, villous architecture, inflammatory cells in the lamina propria, mucosal ulceration and immunohistochemical C4d staining. C4d was scored by a semi-quantitative evaluation of mucosal capillary staining according to the Banff classification for renal allografts; from 0 to 3 (<1% of capillaries= score-0, 1-10% = score-1, 10–50% = score-2, >50% = score-3).
Results. We examined 203 biopsies from the 13 SB allografts recipients (16±4/patient) with DSA transplanted in this period (SB only, n=7; liver+SB, n=4, multivisceral, n=2). All but 2 patients experienced episodes of cellular rejection (from indeterminate to severe). C4d staining was graded as 0-1 in 4 patients, with no vascular or mucosal changes. They received only Intravenous Immunoglobulin (IVIG) (n=3) or IVIG+plasmapheresis (n=1) and had a good clinical outcome. Nine patients had a C4d score-2 (n=5) or 3 (n=4) on at least one biopsy. Five of these patients showed vascular thrombosis, always associated with mucosal ulceration and 2 others showed mucosal ulceration only. Two patients with C4d score-3 (50%) were explanted for refractory humoral rejection despite intensive therapy including Eculizumab for one. Two other patients died for extra-immunological cause. The 5 others had a good outcome with intensive treatment (Steroids, Plasmapheresis, IVIG and Rituximab). In control group without DSA, C4d was graded as 0 or 1 and no vascular changes or mucosal ulceration were noticed.
C4d score-2 or 3 seems to be a good marker of humoral rejection, associated with vascular changes and mucosal ulceration. It may also be a prognostic marker of refractory rejection episodes.