**Figure 3.**

*Factors that govern the acceptance or rejection of an islet transplant.*

HLA (human leukocyte antigens), and they comprise three regions, namely, class I (HLA-A, B, Cw), class II (HLA-DR, DQ, DP) and class III (no HLA genes). For acute rejection of an islet transplant, there is not any established treatment available. And hence transplantation of alloislets with HLAs reactive against even very low levels of preformed alloantibody in the recipient should be avoided even when T and B lymphocyte crossmatches are negative [23, 24].

Association of genetic assessment with demographic and clinical outcomes in a transplantation can potentially enable individualized risk stratification and immunosuppression through the identification of genetic variants relating to immune-mediated complications, post-transplant disease and also alterations in drug-metabolizing genes. Notably, immunosuppressive drug toxicity is of concern as the risk for impairment in kidney function relates with both calcineurin inhibitors and mTOR inhibitors. The drug Tacrolimus predominates immunosuppression in transplantation, and it is metabolized by the cytochrome P 450 3A (CYP3A) subfamily of enzymes in the liver and small intestine. In CYP3A5 gene, a polymorphism in intron 3 alters its expression affecting the enzyme activity and thereby tacrolimus drug metabolism. Tacrolimus drug level correlated well with presence or absence of CYP3A5 polymorphisms. Acute rejection episodes were more frequent in expressers, and they may require higher doses of tacrolimus. When alloislets are transplanted in patients with type 1 diabetes, the use of low-dose tacrolimus in combination with sirolimus is associated with decline in estimated GFR of ~5 mL/min/y/1.73 m<sup>2</sup> . Therefore, CYP3A5 polymorphism analysis before transplant may help determine the optimal dose of tacrolimus in this population and prevent acute rejection episodes or tacrolimus toxicity [7, 25, 26].
