Evaluation of calprotectin levels in intestinal content as a marker for graft rejection

CAGNOLA H; SCAR RAVONATI R; CABANNE A; BIANCHI C; STRINGA P; ERREA A; BITTETI L; MEIER D; CHIRDO F; DOCENA G; GONDOLESI G; RUMBO M

BOLOGNA

Simposio; XI International Small Bowel Transplant Symposium; 2009

Introduction: Diagnosis of rejection after intestinal transplant (ITx) is still performed by biopsy reading; less invasive diagnosis procedures are desirable but not available yet. Calprotectin, a stable cytosolic granulocyte protein, previously used as marker of inflammatory processes, has been proposed as one of the biochemical markers of rejection. The aim of the present work was to evaluate our experience of using calprotectin for monitoring small bowel rejection.   M-M: Calprotectin levels were measured using a commercial ELISA kit on 139 samples of intestinal content randomly collected during endoscopies performed on 11 ITx patients (pts) along 2 years of follow up. Calprotectin determinations were correlated to histological and clinical findings. The cut-off level was determined retrospectively by ROC analysis.   Results: Among the set of samples analyzed, 27 belong to rejection episodes, in accordance to histological/clinical diagnosis; 59 were obtained in the setting of clinical findings with negative biopsies for rejection; and 53 were obtained when no clinical, endoscopic of histologycal findings were reported. A cut-off level of 65 ug of calprotectin/g of intestinal content provided the best assay parameters according to clinical findings: 74 % sensitivity and 43 % of specificity. False positive results were found in pts with gastrointestinal infections (13%), systemic infections (3%), non-specific gastrointestinal symptoms (16%) or unspecific histologycal alterations of the mucosa (19%). Most of the false negative results (71%) were observed during recovery of severe acute rejection episodes successfully treated that were under process of epithelial reconstitution without mucosal infiltration. If this group is excluded, sensitivity rises to 90 %. The other false positive cases correspond to low severity rejection episodes, however, no correlation was observed between calprotectin levels and severity of rejection. Conclusions: This study confirm results obtained form other studies, fecal calprotectin dosage has good sensitivity but low specificity for diagnosing rejection, since high levels can also be found in other clinical conditions. It might be used as a first line of evaluation like other biochemical parameters are used for kidney or liver transplant before considering the need for biopsy.   This work was supported by grants from Agencia Nacional de Promoción de la Ciencia y la Tecnología ANPCYT (PICT 01799), Subsidio Fundación Florencio Fiorini para la Investigación en Ciencias Biomédicas (2006) and National Research Council (CONICET PIP 5241).