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Study to Understand the Genetic Risk of Developing an Immune Response After Blood Transfusions Among Individuals With Sickle Cell Disease

Study to Understand the Genetic Risk of Developing an Immune Response After Blood Transfusions Among Individuals With Sickle Cell Disease

Recruiting
2-99 years
All
Phase N/A

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Overview

The purpose of this research study is to look at genes and determine how they interact with each other to find changes that could explain why some people's immune systems may respond to blood transfusions. This response is called an alloimmune response. We strongly believe that when someone has an alloimmune response, it is caused by changes in their genes. We plan to compare changes in the genes of individuals that develop red blood cell alloimmunization after blood transfusions with those that do not develop alloimmunization. This may help us to create more targeted therapeutic interventions, which may improve the health of alloimmune responders.

Description

Study Description:

This study seeks to fine-map risk variants associated with increased susceptibility to developing red blood cell alloantibodies in patients with sickle cell disease (SCD), with the goal of characterizing the molecular basis of the alloimmunization response. This will allow for improved clinical management for individuals susceptible to alloimmunization responses.

Objectives

Primary Objective:

Elucidate the role of previously identified risk loci in the development of alloantibodies among individuals with SCD.

Secondary Objective:

Validate and characterize additional, novel alloimmunization-related candidate loci.

Endpoints

Primary Endpoint:

Completion of analysis of previously identified risk loci to determine the relationship between genome structure and expression.

Secondary Endpoint:

No additional candidate loci from concurrent discovery studies to evaluate.

Eligibility

  • INCLUSION CRITERIA

To be eligible to participate in this study, an individual must meet all of the following criteria:

  1. Individual (> 2 years of age) with confirmed SCD diagnosis who meets at least one of the following conditions:
    1. History of greater than ten administered transfusions or 20 transfusion units (where known)
    2. History of one or more antibody screens
    3. Known candidate variant genotype

EXCLUSION CRITERIA

An individual who meets any the following criteria will be excluded from participation in this study:

  1. Impaired decision-making capability, with or without a legally authorized representative
  2. History of transplant (e.g., organ, bone marrow, stem cell)
  3. Taking immunosuppressive medications at time of enrollment
  4. Confirmed pregnancy

Study details
    Sickle Cell Disease

NCT06944067

National Human Genome Research Institute (NHGRI)

15 October 2025

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