A 35-year-old Caucasian male with aplastic anemia undergoes bone marrow transplantation. The donor is an HLA-matched sibling. Two weeks after the procedure, he developed a maculopapular pruritic rash predominantly found on his face, hands, and feet. He also complains of diarrhea. The stool is positive for occult blood. Liver function tests are abnormal. Which of the following is this patient's condition's most likely pathophysiologic mechanism?

Options:

A. Activation of the donor T lymphocytes

B. Activation of the donor B-lymphocytes

C. Activation of the host T lymphocytes

D. Virus-induced lymphocyte proliferation

E. Depression of the donor myelopoiesis

Answer: A. Activation of the donor T lymphocytes.

Explanation:

Bone Marrow Transplantation from HLA-matched sibling
↓
Donor T lymphocytes are transferred into the recipient
↓
Donor T cells recognize host antigens as "foreign"
↓
Activation of Donor T lymphocytes
🧠 Release of cytokines (↑ IL-2, IFN-γ)
↓
T-cell mediated attack on host tissues
↓
Target Organs: Skin, GI tract, Liver

↓

Skin → Maculopapular pruritic rash (esp. face, hands, feet)

GI tract → Diarrhea, occult blood in stool

Liver → Abnormal liver function tests
↓
Clinical Features of Acute GVHD

• Rash

• Diarrhea

• Liver dysfunction

Why Other Options Are Wrong?  

B. Activation of the donor B-lymphocytes

↓
Donor B cells activated
↓
Production of donor antibodies
🧠 Antibodies target host tissues
↓
Result: Antibody-mediated rejection (less likely in GVHD)
Why wrong:

• GVHD is primarily mediated by donor T lymphocytes, not B cells.

• B cells are more involved in chronic rejection and antibody-mediated processes, not the acute GVHD response observed in this patient.

C. Activation of the host T lymphocytes

↓
Host T cells recognize donor cells as foreign
↓
Host immune response against donor tissue
🧠 Cytotoxic T cell attack
↓
Result: Graft rejection (Host vs. Graft Disease)
Why wrong:

• In GVHD, the donor's immune cells attack the host's tissues, not vice versa.

• This option describes graft rejection, which is the opposite process of GVHD (where the host attacks the graft).

D. Virus-induced lymphocyte proliferation

↓
Viral infection
↓
Viral antigens activate lymphocytes
🧠 Proliferation of host or donor lymphocytes
↓
Result: Viral illness or infection-related immune response
Why wrong:

• There is no evidence of viral infection in this patient.

• The symptoms and timing fit acute GVHD, not a viral-induced condition.

• GVHD is related to immune reaction post-transplant, not viral proliferation.

E. Depression of the donor myelopoiesis

↓
Suppressed production of myeloid cells in donor marrow
🧠 Decreased production of neutrophils, monocytes, etc.
↓
Result: Leukopenia, increased infection risk
Why wrong:

• This describes issues with blood cell production (myelopoiesis) but does not explain the skin rash, diarrhea, or liver dysfunction.

• The symptoms are due to donor T-cell activation, not a lack of donor blood cell production.

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