CVID and TfHopathies

Question 1

What are the hallmarks of CVID?

Answer 1

1. Hypogammaglobulinemia
2. Impaired B cell differentiation into plasma cells and memory cells
3. (Generally) normal B cell levels

CVID can be thought of as a qualitative B cell defect

Question 2

Diagnostic criteria for CVID

Answer 2

Question 3

Monogenic etiologies of CVID

Answer 3

• BAFF Receptor
• ICOS
• CTLA-4
• PI3K
• LRBA (lipopolysaccharide-responsive beige-like anchor)

Question 4

Autoimmunity in CVID

Answer 4

Occurs in ~25% of cases

Associated with the presence of a CD21^low , CD38^low population of B cells which exhibit autoreactivity.

ITP and Immune hemolytic anemia are the most common, but many different autoimmune diseases have been reported.

Question 5

Hallmark expression of TfH cells

Answer 5

• CXCR5 (GC follicle targeting, CXCL13 responsive)
• BCL-6
• CD40L
• ICOS
• IL-21 production

Question 6

TfH1, TfH2, and TfH17

Answer 6

Produce the respective cytokine profiles.

TfH2 and TfH17 are considered efficient helpers, while TfH1 are non-efficient.

This is mostly due to differences in IL-21 secretion: TfH1 is a poor secreter of IL-21.

Question 7

Role of T_fRegs

Answer 7

Perform two important regulatory roles at the GC:

Limit the extent of the GC response (amount of proliferaiton)

May terminate the GC repsonse entirely.

Question 8

Characteristics of the main TfH subsets

Answer 8

Question 9

Monogenic mutations resulting in reduced TfH number

Answer 9

• STAT3
• IL10-R
• CD40LG
• BTK
• NEMO (NfkB Essential Modulator, aka IkB kinase)