Immunodeficiency: hyper-IgM syndrome: practice question

A Pathology question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Pathology · Immunodeficiency: hyper-IgM syndrome

Sample item

A 3-year-old boy has recurrent pyogenic sinopulmonary infections and Pneumocystis jirovecii pneumonia. Serum IgG, IgA and IgE are low, IgM is normal to high, B-cell numbers are normal and lymph nodes lack germinal centres. Which defect is most likely?

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

D. Defective CD40 ligand on activated CD4 T cells, impairing immunoglobulin class switching

In X-linked hyper-IgM syndrome, CD40 ligand on helper T cells fails to engage CD40 on B cells and macrophages. B cells cannot switch from IgM to other classes, germinal centres do not form, and macrophage activation is impaired, which explains susceptibility to Pneumocystis. IgM is therefore normal or raised while other classes are low.

Option by option

  • A. Mutation of Bruton tyrosine kinase, blocking pre-B cell maturation

    BTK mutation gives absent B cells and low levels of all immunoglobulin classes.

  • B. Deficiency of adenosine deaminase, causing lymphocyte toxicity

    Adenosine deaminase deficiency causes severe combined immunodeficiency with profound lymphopenia.

  • C. Defective NADPH oxidase, preventing the respiratory burst

    NADPH oxidase defect causes chronic granulomatous disease with catalase-positive infections.

  • D. Defective CD40 ligand on activated CD4 T cells, impairing immunoglobulin class switching (correct)

    Correct. The CD40L defect blocks class switching and germinal centre formation.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

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Questions about this Pathology question

What is the answer to this Pathology question?

The best answer is D, Defective CD40 ligand on activated CD4 T cells, impairing immunoglobulin class switching. In X-linked hyper-IgM syndrome, CD40 ligand on helper T cells fails to engage CD40 on B cells and macrophages.

Why is "Mutation of Bruton tyrosine kinase, blocking pre-B cell maturation" not the answer?

BTK mutation gives absent B cells and low levels of all immunoglobulin classes.

Why is "Deficiency of adenosine deaminase, causing lymphocyte toxicity" not the answer?

Adenosine deaminase deficiency causes severe combined immunodeficiency with profound lymphopenia.

Why is "Defective NADPH oxidase, preventing the respiratory burst" not the answer?

NADPH oxidase defect causes chronic granulomatous disease with catalase-positive infections.

What concept does this question test?

It tests Immunodeficiency: hyper-IgM syndrome in Pathology. B cells cannot switch from IgM to other classes, germinal centres do not form, and macrophage activation is impaired, which explains susceptibility to Pneumocystis. IgM is therefore normal or raised while other classes are low.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Immunodeficiency: hyper-IgM syndrome?

Learn each disease as a bundle: cause, key histology, markers, and the clinical hallmark. Then use the flashcards and the other Pathology questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.