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Graft-versus-host disease, HLA typing and tumor immunology

10 ASCP MLS practice questions on Graft-versus-host disease, HLA typing and tumor immunology, part of Immunology. The first 10 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

  1. Question 1 · Hard

    A 68-year-old man has adenocarcinoma of the pancreatic body, with several liver metastases on CT and biopsy. His bilirubin is normal. Results: CA 19-9 below 2 U/mL (reference < 37 U/mL), unchanged when the sample is retested at a 1:10 dilution; CEA 22 ng/mL [22 µg/L] (reference < 5); assay controls within limits. He takes no supplements. A blood bank sample sent before a planned procedure types as group O, D-positive, Le(a-b-), with a negative antibody screen. The CA 19-9 result is best explained by:

    1. AA high-dose hook effect
    2. BA Lewis-negative phenotype
    3. CBiotin interference
    4. DHeterophile antibody interference
    Show answer

    Answer: B · A Lewis-negative phenotype

    CA 19-9 is sialyl Lewis a, a carbohydrate that can be made only when the Lewis fucosyltransferase (FUT3) adds fucose to a type 1 chain. About 5 to 10% of people, more in some populations, lack a working FUT3 gene and type Le(a-b-), and they cannot make CA 19-9 however large their tumor. In such patients a normal CA 19-9 is meaningless, and CEA or imaging is used to follow the cancer. A hook effect is excluded because the 1:10 dilution did not raise the result, and biotin is unlikely with no supplements. Heterophile antibodies more often raise sandwich assay results falsely and would not explain the Lewis type.

    • A: A hook effect would give a higher result after dilution, and the 1:10 retest was unchanged.
    • C: He takes no supplements, so biotin interference is unlikely.
    • D: Heterophile antibodies usually raise sandwich results falsely and do not explain the Le(a-b-) type.
  2. Question 2 · Easy

    Acute graft-versus-host disease after an allogeneic stem cell transplant mainly damages the:

    1. ABone marrow, spleen and lymph nodes
    2. BSkin, liver and gastrointestinal tract
    3. CBrain, spinal cord and nerves
    4. DKidneys, heart and lungs
    Show answer

    Answer: B · Skin, liver and gastrointestinal tract

    In GVHD, donor T cells in the graft recognize the recipient's HLA and minor histocompatibility antigens as foreign. The main targets are the skin (rash), liver (raised bilirubin) and gut (diarrhea), and the grade is based on these three organs. The marrow is spared because after a stem cell transplant it is donor-derived. Prevention relies on HLA matching and immunosuppression.

    • A: After stem cell transplant the marrow is donor-derived, so it is not attacked.
    • C: The nervous system is not a main target of acute GVHD.
    • D: Kidneys, heart and lungs are the grafts rejected in solid organ transplants.
  3. Question 3 · Easy

    After surgery for colorectal cancer, recurrence is usually monitored with serial measurement of:

    1. ACA 125
    2. BCarcinoembryonic antigen (CEA)
    3. CAlpha-fetoprotein (AFP)
    4. DCA 15-3
    Show answer

    Answer: B · Carcinoembryonic antigen (CEA)

    CEA is a glycoprotein raised in many colorectal cancers, and serial levels every few months after resection help detect recurrence or metastasis. It is not used for screening, because it can be raised in smokers and in inflammatory bowel disease or cirrhosis, and is often normal in early cancer. A rising trend after an initial fall is more meaningful than a single value. Serial samples should be tested by the same method.

    • A: CA 125 is used mainly for epithelial ovarian cancer.
    • C: AFP is used for hepatocellular carcinoma and germ cell tumors.
    • D: CA 15-3 is used mainly for breast cancer.
  4. Question 4 · Medium

    For an unrelated-donor hematopoietic stem cell transplant, the usual standard for a well-matched donor is a high-resolution match at:

    1. AHLA-A, -B and -DR by serology (6 of 6)
    2. BHLA-DQ and -DP only (4 of 4 alleles)
    3. CHLA-A, -B, -C and -DRB1 (8 of 8 alleles)
    4. DHLA-A and -B only (4 of 4 alleles)
    Show answer

    Answer: C · HLA-A, -B, -C and -DRB1 (8 of 8 alleles)

    Unrelated stem cell donors are matched at the allele level, by DNA typing, at HLA-A, -B, -C and -DRB1: two alleles at each of four loci, an 8/8 match. Each allele mismatch raises the risk of GVHD and graft failure and lowers survival. DQB1 and DPB1 are often typed as well when choosing between donors. Antigen-level matching at A, B and DR is the older approach used in kidney transplantation.

    • A: Serologic A, B and DR matching is too coarse for stem cell transplants.
    • B: DQ and DP are secondary loci; A, B, C and DRB1 matter most.
    • D: HLA-C and -DRB1 mismatches also raise the risk of GVHD.
  5. Question 5 · Medium

    In a man with a total PSA of 6.2 ng/mL [6.2 µg/L], which additional result most favors prostate cancer over benign prostatic hyperplasia?

    1. APSA density 0.05 ng/mL per cm3
    2. BFree PSA 7% of total PSA
    3. CFree PSA 32% of total PSA
    4. DPSA velocity 0.1 ng/mL per year
    Show answer

    Answer: B · Free PSA 7% of total PSA

    In prostate cancer a larger share of PSA circulates bound to alpha-1-antichymotrypsin, so the free fraction is low. In the 4 to 10 ng/mL range, free PSA below about 10% carries a much higher chance of cancer, while above about 25% the chance is low. A slow rise over time and a low PSA per unit of gland volume also favor benign enlargement. Free PSA is unstable, so serum should be separated and tested or frozen promptly.

    • A: A low PSA density favors benign enlargement of a large gland.
    • C: A high free fraction favors benign enlargement.
    • D: A slow yearly rise favors a benign cause.
  6. Question 6 · Medium

    A woman waiting for a kidney transplant has a calculated panel reactive antibody (cPRA) of 98%. What does this mean?

    1. AHer antibodies react with 98% of her own lymphocytes
    2. BAbout 98% of donors would carry an unacceptable HLA antigen
    3. CShe has a 98% chance of hyperacute rejection of a graft
    4. DAbout 98% of her HLA antibodies are directed at class I

    Answer and explanation in LearnFree account

  7. Question 7 · Easy

    Assuming no recombination, what is the chance that a full sibling is HLA-identical to a patient?

    1. A25%
    2. B75%
    3. C50%
    4. D12.5%

    Answer and explanation in LearnFree account

  8. Question 8 · Hard

    After orchiectomy for a nonseminomatous germ cell tumor, serum AFP falls from 1,600 ng/mL [1,600 µg/L] to 1,200 ng/mL [1,200 µg/L] over 14 days. AFP has a half-life of about 5 to 7 days. What does this most suggest?

    1. AA seminoma component producing AFP
    2. BAFP from tumor cells dying after surgery
    3. CResidual nonseminomatous tumor making AFP
    4. DThe expected fall after complete removal

    Answer and explanation in LearnFree account

  9. Question 9 · Hard

    HLA typing in a family: patient A1, A2; B8, B44. Father A1, A3; B7, B8. Mother A2, A24; B35, B44. A sibling types A1, A24; B8, B35. Assuming no recombination, the sibling is:

    1. ASharing no haplotype with the patient
    2. BHLA-identical to the patient
    3. CHaploidentical, sharing the paternal haplotype
    4. DHaploidentical, sharing the maternal haplotype

    Answer and explanation in LearnFree account

  10. Question 10 · Medium

    Which tumor marker is most useful for monitoring hepatocellular carcinoma and nonseminomatous germ cell tumors?

    1. ACA 125
    2. BAlpha-fetoprotein (AFP)
    3. CCA 19-9
    4. DCarcinoembryonic antigen (CEA)

    Answer and explanation in LearnFree account

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