A 50-year-old previously healthy man is evaluated for progressive fatigue, weakness, and recurrent gingival bleeding. Laboratory studies reveal normocytic normochromic anemia, thrombocytopenia, and leukocytosis with circulating myeloblasts. Bone marrow biopsy establishes a diagnosis of acute myeloid leukemia. Induction chemotherapy followed by allogeneic hematopoietic cell transplantation (HCT) is planned. Molecular typing of human leukocyte antigen (HLA) -A, -B, -C, -DP, -DQ, and -DR is performed. The patient's biological sister, with whom he shares both parents, is eligible for stem cell donation and undergoes HLA typing. Which of the following is the most likely probability that the sibling will be an identical HLA match with this patient?

Question

A 50-year-old previously healthy man is evaluated for progressive fatigue, weakness, and recurrent gingival bleeding.  Laboratory studies reveal normocytic normochromic anemia, thrombocytopenia, and leukocytosis with circulating myeloblasts.  Bone marrow biopsy establishes a diagnosis of acute myeloid leukemia.  Induction chemotherapy followed by allogeneic hematopoietic cell transplantation (HCT) is planned.  Molecular typing of human leukocyte antigen (HLA) -A, -B, -C, -DP, -DQ, and -DR is performed.  The patient's biological sister, with whom he shares both parents, is eligible for stem cell donation and undergoes HLA typing.  Which of the following is the most likely probability that the sibling will be an identical HLA match with this patient?

Quizplus · Accepted Answer

11ec160b_376a_57cb_9249_f1b86a2589b8_MD0001_00 The human leukocyte antigen (HLA) genes encode major histocompatibility complex (MHC) molecules that are expressed on the cell surface and are key to recognition of cells as self or non-self by the immune system. These include major class I genes (eg, HLA-A, HLA-B, HLA-C) and class II genes (eg, HLA-DP, HLA-DQ, HLA-DR), along with other minor HLA genes. Although there are thousands of HLA alleles in the human population with millions of potential combinations, the HLA genes are clustered within a short region of a single chromosome. This results in a low rate of crossover, allowing the HLA gene cluster to be treated as an HLA haplotype (a series of linked genes on the same chromosome). Each child inherits 2 HLA haplotypes, one from the mother and one from the father. Therefore, the probabilities that a given sibling will share some or all of the same HLA genes are as follows: Molecular typing of HLA antigens is performed prior to transplants (eg, allogeneic stem cell transplant) to evaluate potential donors for mismatch in HLA alleles (eg, HLA-DR8 versus HLA-DR3), which is associated with higher rates of posttransplant complications (eg, graft versus host disease, graft failure). An HLA-identical sibling donor would drastically reduce the likelihood of serious complications and increase the likelihood of a successful transplant. Educational objective: The human leukocyte antigen (HLA) genes encode major histocompatibility complex (MHC) molecules that are key to activation of the immune system in response to foreign (non-self) antigens. All the HLA genes are clustered together, meaning that there is a low rate of crossover and that offspring essentially inherit 2 HLA haplotypes, one from each parent. Therefore, the probability that a sibling would be an identical HLA match is 1/4.

A 50-Year-Old Previously Healthy Man Is Evaluated for Progressive Fatigue