Combined Immunodeficiency

Question 1

What does combined mean?

Answer 1

As a consequence, they have low numbers of T cells and natural killer cells, and their B cells do not function.

Question 2

SCID:

Age of onset?

What cells are deficient?

2 common locations for infection?

Can have a range of presentations? - Similar to before

INV:

• What lymphocytes will be low?
• What would you expect the Ig levels to be?

Answer 2

Gut and U/LRTI - Pneumocystis

4-6 months after birth

CD3/4/8 (CD 19 may be low)

All should be low - lack of B cells - lack of antibody production

IgG may be low normal due to some maternal antibodies still left!

Question 3

Omenn Syndrome:

What feature on bloods means it is Omenn’s syndrome?

What happens to the babies skin?

They also have:

• Emerging lymphadenopathy
• Emerging hepatosplenomegaly

T cells infiltration occurs which infitarate what tissues?

Appears like graft and host disease!

Answer 3

Generalised scaly erythroderma

CID with Hypereosinophilia

Liver + Spleen - hepatosplenomegaly

Skin - Generalised scaly erythroderma

Question 4

CD40L Deficiency:

CD40L (ligand) is expressed primarily by activated T cells, as well as activated B cells and platelets; and under inflammatory conditions is also induced on monocytic cells, natural killer cells, mast cells, and basophils

Same symptoms as before!

What blood results do you expect?

How can you confirm this?

Answer 4

Normal CD19 - B cells
Lack of Mature B cells

Raised IgM, low/absent IgA, IgG

Look for CD40L expression - Reduced/absent CD40L expression

B cells are there but they are not working well due to a lack of CD40L expression - needed for activation!

Question 5

DOCK 8 Deficiency:

Answer 5

Dedicator of Cytokinesis 8 (DOCK8) deficiency is a combined immunodeficiency that exemplifies the broad clinical features of primary immunodeficiencies (PIDs), extending beyond recurrent infections to include atopy, autoimmunity and cancer.

Question 6

Classic ‘PID’ is associated with malignancy:

What do the following PID increase the risk of?

• SCID
• Wiskott-Aldrich syndrome
• CD40L
• DOCK8
• XLA
• Common variable ID

Answer 6

Lymphoma for everything except CD40L deficiency!!