Immune monitoring in small bowel transplantation.
OBJECTIVE
Immune monitoring is needed in small bowel transplantation (SBTx) because of a high incidence of rejection and graft loss, and life-threatening complications of high-dose prophylactic immunosuppression.


RESULTS
Clinical tests relevant to SBTx include methods to detect antidonor human leukocyte antigen antibodies, among which those which use known purified human leukocyte antigen peptides as substrates correlate best with graft loss; enumerate peripheral lymphocyte subsets to determine the efficacy of lymphocyte-depleting antibodies; estimate general immune function based on ATP production by mitogen-stimulated T-helper cells. Research tests that show clinical utility in SBTx recipients include following markers. First, flow cytometric mixed leukocyte responses, which detect donor-induced proliferation of recipient T-cytotoxic cells by dilution of the intravital dye carboxyfluorescein succinimidyl ester, or donor-induced CD154 expression in recipient T-cytotoxic memory cells. Among such tests, CD154 T-cytotoxic memory cells achieve the highest known sensitivity and specificity of at least 90% for the detection of acute cellular rejection. Second, elevated fecal calprotectin, an early screening marker for intestinal inflammation, which can indicate the need for a SBTx biopsy, especially after ileostomy stoma closure. Third, single-nucleotide polymorphisms associated with inflammatory bowel diseases, for example, nucleotide-binding oligomerization protein, macrophage stimulating 1, and so on. These single-nucleotide polymorphisms may be used to select the rejection-prone SBTx recipient for more potent immunosuppression, if additional studies confirm their associations with outcomes.


CONCLUSIONS
The final approach to monitor the SBTx recipient will likely involve using the method(s) with the best sensitivity and specificity for detecting acute cellular rejection or graft loss during time periods when such events are most likely.
Sindhi
Rakesh
R
Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA. rakesh.sindhi@chp.edu
AshokKumar
Chethan
C
Mazariegos
George
G
Nayyar
Navdeep
N
Ningappa
Mylarappa
M
Soltys
Kyle
K
Bond
Geoffrey
G
Sun
Qing
Q
Humar
Abhinav
A
Abu-Elmagd
Kareem
K
Zeevi
Adriana
A
D001681:Biological Assay; D003601:Cytotoxicity Tests, Immunologic; D016903:Drug Monitoring; D005819:Genetic Markers; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism; D007421:Intestine, Small / Q000276:immunology / Q000637:transplantation*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D015166:Monitoring, Immunologic / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012778:Short Bowel Syndrome / Q000601:surgery*; D013997:Time Factors; D016896:Treatment Outcome
D005819:Genetic Markers; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators