Non-Invasive Immune Monitoring of Intestinal Transplant Recipients: A pilot examination of immunoglobulin levels, lymphocyte subsets, and calprotectin

Introduction: Rejection (ACR) and infectious enteritis (IE) remain formidable obstacles to successful intestinal transplantation (ITx). While endoscopy/biopsy, and stool studies remain the gold standard for diagnosis and treatment, each have limitations. Development of a non-invasive monitoring assay(s) is crucial. To this end, several tests have been proposed but none widely validated. In this study, we examined the use of several immune monitors for diagnosis of ACR or IE. Materials: A retrospective review of a single-center prospective database of ITx recipients was undertaken between May 2013 and July 2016. The first 12 post-ITx weeks were examined. Protocol monitoring of ITx included: weekly IgA, IgG, CD4, CD8, and calprotectin levels. Protocol biopsy included weekly endoscopy/biopsy starting in the second post-ITx week. ACR was graded per ITx standard. Stool studies were sent for allograft dysfunction and IE diagnosed based on positive results. Induction immunosuppression was either IL2RA or ATG based. Results: 14 patients were included; 7 adults; 4 intestine only, 2 liver-intestine, 6 multivisceral, 2 modified multivisceral. There were 3 patients with ACR-/IE-; 5 ACR+/IE-; 3 ACR-/IE+; 3 ACR+/IE+. During the study interval, average IgG levels were low normal; average IgA levels were below normal; average CD4 and CD8 levels were below normal; and average calprotectin levels were within normal ranges. The median time to first ACR was 29 days. The median time to first IE was 43 days. For ACR+ there was a significantly higher average IgA level in the 4 weeks prior to ACR (136 vs 102, p=0.02). There was a trend toward higher CD4 (305 vs 176, p=0.16) and CD8 (272 vs 190, p=0.34) levels in ACR. There were no difference in IgG and calprotectin. For IE+, there was a significantly higher average CD4 (360 vs 190, p=0.007) and CD8 (358 vs 144, p=0.003) levels in the 6 weeks prior to IE. There were no difference in IgG, IgA and calprotectin. Conclusions: This pilot study is the first to examine IgA, IgG, CD4, CD8, and calprotectin levels in ITx. Lymphocyte subsets did show consistent differences in patients with ACR+ and IE+. This may be related to either immunosuppression or immune reactivity. Ig levels were less consistent and can be impacted by supplemental IVIG therapy was well as protein losses. Further expansion of this study is required to validate these conclusions but this study introduces other non-invasive immune monitoring tests.FigureFigure