0528 - Genomic Susceptibility to Infection

Question 1

What is the major determinant of susceptibility to infection?

Answer 1

The host response - hence why two people can have different outcomes in the same household from the same infection. It is the most significant physiological failing in humans.

Question 2

How do antibody defects present?

Answer 2

Primarily present with recurrent respiratory tract infections by encapsulated organisms (e.g. HiB, Pneumococcus mainly). But it’s to a relatively narrow group of organisms.

Question 3

Briefly outline congenital agammoglobulinaemia.

Answer 3

Present with no antibodies at all, around 6-12 months of age (post-maternal Ig’s). Causes recurrent bacterial infections with HiB, S. Pneumoniae, cellulitis, and enterovirus encephalitis.
X-linked recessive in most cases - Bruton Tyrosine Kinase gene mutation. Causes arrested maturation of B-cells in the bone marrow.

Question 4

Briefly outline common variable immune deficiency (CVID)

Answer 4

Cluster of disorders characterised by hypogammaglobulinaemia. General onset in late childhood or early 20s, but occurs at any age - therefore not just congenital.
Leads to qualitively or quantitatively impaired B-cells, and subsequent infection by encapsulated organisms. Paradoxically prone to autoimmune conditions.

Question 5

Briefly outline Congenital T-cell deficiency/SCID

Answer 5

Dramatic presentation, 3-6 months of age, with severe infections, severe candidiasis, PCP, herpes viruses, intractable diarrhoea, and fungal infections.
Lack of T-cells leads to secondary B-cell defects, leading to impaired cellular and humoural immunity. Lymphoid tissue is often hypoplastic.

Question 6

What is the most common Ig deficiency?

Answer 6

IgA - 1 in 400, but often asymptomatic.

Question 7

How do genetic immune deficiencies present?

Answer 7

The underlying genetic mutation will present with susceptibility to specific infection - a specific group of organisms that is able to take hold because of the effects of that mutation, it’s not just a case of infections everywhere.
Infection is not bad luck - it’s a phenotype arising from genetic susceptibility and environmental threat.
Spectrum of infections encountered is determined by the nature of the defect.