Primary Immunodeficiency Syndromes

Question 1

X-linked Agammaglobinemia (Bruton’s Aggammaglobulinemia)

Answer 1

-Failure of B-cell precursors (pro-B and pre-B cells) to develop into mature B cells. This defect is due to a mutation in an X-linked gene which codes for cytoplasmic tyrosine kinase requires for B cell maturation (Bruton tyrosine kinase (Btk))

Question 2

Common Variable Immunodeficiency:

Answer 2

-Heterogenous group of disorders characterized by failure of B cells to differentiate into plasma cells. These patients have decreased Ig production. B cells cannot mature into plasma cells. B cell lymphoid areas (germinal centers) are hyper plastic.

Question 3

Isolated IgA Deficiency:

Answer 3

-Failure of B cells to differentiate into IgA producing plasma cells. As a result, serum and secretory IgA levels are decreased. The molecular defects involve are mostly unknown.

Question 4

What is DiGeorge Syndrome?

Answer 4

Thymic hypoplasia

-T cell deficiency due to failure of development of the third and fourth pharyngeal pouches

Question 5

What is Hyper-IgM syndrome?

Answer 5

• Patients are able to make IgM but are deficient in their ability to make IgG, IgA and IgE antibodies (defect in immunoglobulin class switching, i.e. failure of B cells to switch from IgM to other classes of immunoglobulins)
• Lab usually shows normal to elevated levels of IgM, no IgA or IgE and very low levels of IgG.
• About 70% of individuals have X-linked receive mutations in gene encoding CD40 ligand

Question 6

What is Severe Combined Immunodeficiency (SCID)?

Answer 6

• Group of syndromes having in common profound defects of both humoral and cell mediated immunity.
• Without hematopoietic cell transplantation, death occurs within a year
• Many different genetic lesions can give rise to SCI. Most common form (50-60% cases) is X-linked and due to a mutation in the gene encoding the common gamma-chain subunit of cytokine receptors

Question 7

What is immunodeficiency with thrombocytopenia and Eczema (Wiskott-Aldrich Syndrome)?

Answer 7

-X-linked recessive disorder characterized by thrombocytopenia, eczema, and a marked vulnerabiliy to recurrent infection, resulting in premature death.

Question 8

What is X-linked lymphoproliferative syndrome?

Answer 8

Characterized by inability to eliminate EBV, leading to severe and sometimes fatal infectious mononucleosis and B cell lymphomas!