Analysis of Pig-MAP After Small Bowel Transplantation in Pigs A. Escartı´n, J. Bueno, F. Lampreave, N. Gonza ´ lez-Ramo ´ n, A. Pin ˜eiro, I. Cruz, and F.A. Garcı´a-Gil R ECENT studies have shown that the pig-MAP alpha-2 globulin is a pig acute phase protein that increase after injuries. 1,2 This protein has been recently cloned and it is homologous to a new human plasma protein called PK-120 (plasma kallikrein-sensitive protein)/IHRP (Inter- -trypsin inhibitor human-related protein). 3–5 The aim of this study has been to investigate the response of pig-MAP serum level after small bowel transplantation (SBT). MATERIALS AND METHODS Twenty-nine female Landrace pigs (mean weight, 26  9 kg) underwent total ortothopic SBT except for 5 cm of proximal jejunum and terminal ileum. The small bowel graft was based on a vascular pedicle of superior mesenteric artery (SMA) and superior mesenteric vein (SMV) which were anastomosed end-to-end to recipient SMA and SMV respectively. Intestinal reconstruction was performed with jejuneal end-to-end and ileal end-to-end anasto- mosis. A gastrostomy was performed to allow drugs administration. Animals were divided in four groups: group I (n = 7) autotrans- plantation; group II (n = 6) allotransplantation without immuno- suppression; group III (n = 9) allotransplantation under cyclospo- rine (CyA) 15 mg/kg/d IV for 7 days then 30 mg/kg/d OS; group IV (n = 7) allotransplantation under FK506 0.3 mg/kg/d IM for 7 days then 0.3 mg/kg/d OS. Animals were sacrificed after 45 days or more from the date of transplantation or when they lost more than 40% of their preoperative body weight. Biopsies and histopathologic studies were done in all animals at the time of autopsy. Serum concentration of pig-MAP was determined in pigs serum by radial immunodiffusion in 1% agarose gels containing the specific rabbit antiserum against the protein. Purified pig-MAP was used as a reference standard. Samples were obtained daily during first week, then twice a week. RESULTS The autotransplantation group was considered as control of response of pig-MAP to the surgical procedure. All animals survived 5 days or more except in group II. Survival and histologic findings in autopsy are detailed in Table 1. Pig-MAP increased in all animals during posttransplanta- tion days 1 to 5 (Fig 1). After the fifth day, groups II and III showed a continual rise in pig-MAP while levels of pig- MAP in groups I and IV decreased to normal values (P  .05 in groups II and III versus groups I and IV). According to the grade of rejection (Fig 2), pig-MAP levels were higher in animals with severe and moderate grade than in the control group (P  .05). DISCUSSION The clinical practice of intestinal transplantation was dramatically changed by the emergence of FK506 as the principal immunosuppressive drug. 6 However, rejection is still the main cause of morbidity and mortality. No serologic marker of rejection has been found yet. Sur- veillance with endoscopy and biopsy are needed in order to detect it in an early phase. In a recent study in pigs, a major acute phase serum protein in pigs (pig-MAP) was found, which has not been previously described in this or in other species. 1 We have found homology between the pig-MAP and a newly de- scribed human serum protein, denominated PK-120/IHRP, and the porcine IHRP. 3–5 This human protein homolog is thought to be an acute phase protein that significantly increases in the serum of patients after surgical trauma. 2 After SBT, the pig-MAP values rise quickly as a response to surgical trauma in all groups. Pig-MAP levels were significantly higher in animals without immunosuppression or treated with CyA than in those treated with FK506 and autotransplantation. These levels were related to a worsen- ing clinical course and lower survival. Also, higher levels of pig-MAP were found when the histologic degree of rejec- From Unidad Mixta de Investigacio ´ n (Hospital Clı ´nico-Fac- ultad de Medicina) y Departamento de Bioquı ´mica y Biologı ´a Molecular y Celular (Facultad de Ciencias), University of Zara- goza, Zaragoza, Spain. This work was supported by research grants PCM4494 from CONSID (Diputacio ´n General de Arago ´ n) and University of Zaragoza. Address reprint requests to Dr Alfredo Escartı´n, C./ Cervantes, 26 –28, 3°F, 50006 Zaragoza, Spain. e-mail: escartin @posta. unizar.es. Table 1. Survival and Histologic Findings at Autopsy Group 45-Day Survival* MS ACR Mild Moderate Severe I (n = 7) 100% 63  16 — — — II (n = 7) 0% 8.3  3 0 0 7 III (n = 7) 22% 29  24 0 3 4 IV (n = 8) 85.7% 48  15 4 3 1 MS, mean survival in days; ACR, acute celular rejection at the time of autopsy. *(P  .05). 0041-1345/98/$19.00 © 1998 by Elsevier Science Inc. PII S0041-1345(98)01430-4 655 Avenue of the Americas, New York, NY 10010 4334 Transplantation Proceedings, 30, 4334–4336 (1998)