Umbilical cord blood transplantation and the impact of the CTLA4 genotype on outcomes

ABSTRACT

Background: Umbilical cord blood transplantation is an effective method of curing multiple diseases when there is no donor available for allogeneic hematopoietic stem cell transplantation (AHSCT). It has been recently suggested that polymorphisms in genes affecting antigen presentation could potentially affect cord blood transplantation (CBT) outcomes.

Areas covered: In this review, we present the results of the latest studies investigating the link between CTLA4 gene variability and umbilical cord blood transplantation outcomes.

Expert opinion: The search for genetic variants that influence the immune response, both innate and adaptive immunity, may lead to more optimal therapies. Promising candidate genes are those that regulate the expression of proteins associated with T-cell activation. Many genetic variants could be therapeutically important, including those related to innate and adaptive immunity, cytokines, chemokines, drug-metabolizing enzymes, drug transporters, and inflammatory enzymes. The development of an algorithm that includes the determination of selected genetic variants could be helpful for an appropriate donor–recipient CBT matching.

KEYWORDS:

• CTLA4
• AHSCT
• CBT
• GVHD
• blood

Article highlights

• CBT is an alternative to AHSCT, and it is performed in situations where no HLA-paired donor is available.

• Pathogenesis of GVHD—which is a common and potentially lethal complication of AHSCT—lies within the function of proteins responsible for the presentation of antigens: HLA, costimulatory second signal, and CTLA4.

• In recent years, the hypothetical influence of many common CTLA4 polymorphisms on AHSCT outcomes has been verified.

• Rs3087243 GG genotype of the CTLA4 gene polymorphism could become a useful biomarker in the process of cord blood (CB) selection.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.