Clinical Immunology—Bone Marrow Transplant in SCID (Severe Combined Immunodeficiency) For an infant diagnosed with SCID who is receiving a bone marrow (hematopoietic stem cell) transplant, which condition is essential for the donor graft to minimize complications and ensure engraftment?
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ABe irradiated to eliminate graft-versus-host disease (GVHD)
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BContain abundant mature T cells to initiate immediate immune responses
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CCome from a donor who shares key MHC (HLA) alleles with the recipient
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DCome specifically from one of the child's parents
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EBe depleted of all B cells but retain mature T cells
Answer
Correct Answer: Come from a donor who shares key MHC (HLA) alleles with the recipient
Explanation
Introduction / Context:Severe Combined Immunodeficiency (SCID) is a life-threatening condition characterized by profound defects in T-cell function with variable B- and NK-cell impairment. Curative therapy often involves hematopoietic stem cell transplantation (HSCT). A central principle for HSCT success is appropriate donor–recipient MHC (HLA) matching to promote engraftment and reduce the risk of graft-versus-host disease (GVHD). This question tests understanding of which requirement is essential (“must”) for bone marrow given to an infant with SCID.
Given Data / Assumptions:
- Recipient: infant with SCID requiring HSCT.
- Outcome goals: successful engraftment, immune reconstitution, low GVHD risk.
- Clinical practice emphasizes HLA compatibility and careful management of mature donor T cells.
Concept / Approach:HSCT success hinges on matching histocompatibility antigens (MHC/HLA). T-cell allorecognition of mismatched HLA is a primary driver of GVHD. While partial (haploidentical) related donors can be used with T-cell depletion, some level of HLA matching remains indispensable to balance engraftment and GVHD risk. Irradiating the graft itself would destroy stem cells; instead, selective T-cell depletion or careful donor selection is used to manage GVHD risk.
Step-by-Step Solution:
Step 1: Identify the non-negotiable factor for engraftment and GVHD mitigation: compatibility at key HLA loci.Step 2: Evaluate “irradiated graft”: irradiation would ablate stem cell viability, so this is not standard practice for the graft (blood products for SCID may be irradiated to prevent transfusion-associated GVHD, but not the stem-cell graft).Step 3: Evaluate “mature T cells must be present”: mature donor T cells increase GVHD risk; many protocols purposefully deplete them.Step 4: Evaluate “must come from a parent”: parents are convenient haploidentical donors but a matched sibling or unrelated HLA-matched donor is often preferable; thus “parent” is not mandatory.Verification / Alternative check:Clinical HSCT protocols prioritize highest feasible HLA match; where full match is impossible, graft manipulation (e.g., T-cell depletion) is performed, underscoring that HLA matching is the indispensable requirement.
Why Other Options Are Wrong:
- Irradiating the graft would inactivate stem cells.
- Including many mature T cells heightens GVHD risk.
- Requiring a parent donor is unnecessary; matched sibling/unrelated donors are acceptable.
- B-cell depletion alone does not address GVHD risk; T cells are the main concern.
Common Pitfalls:Confusing irradiated blood products with irradiating the stem-cell graft; assuming kinship guarantees better outcomes regardless of HLA matching.
Final Answer:Come from a donor who shares key MHC (HLA) alleles with the recipient