Primary Immunodeficiency Disorders

Question 1

What is the pathogenesis of X-linked SCID?

Answer 1

mutation in gamma chain of IL-2 receptor

Question 2

What is the common feature in all SCID?

Answer 2

Absent/non-functional T cells

Question 3

What is the newborn screening test of SCID?

Answer 3

TRECs – non-replicating pieces of DNA in naive T cells generated when making a TCR; number decreased in all SCID and T cell lymphopenia

Question 4

What is the main gene affected in DiGeorge Syndrome?

Answer 4

TBX1

Question 5

CATCH-22 Mnemonic for DiGeorge

Answer 5

Cardiac Defects
Abnormal facies (microagnathia, low set ears, fish-shaped mouth) 
Thymic hypoplasia
Cleft palate
Hypocalcemia
22nd chromosome

Question 6

Developmentally, where is the defect in DiGeorge syndrome?

Answer 6

1st-6th pharyngeal pouches

Question 7

Who do you recommend testing for 22q/DS??

Answer 7

ALL infants with significant heart defects

Unexplained lymphopenia

Question 8

What is the common presentation of XLA?

Answer 8

Boy
No B cells
Recurrent pulmonary infections

Question 9

What genetic mutation is present in XLA?

Answer 9

Mutations in Bruton’s Tyrosine Kinase Gene (Btk) results in failure in the differentiation of B cells –> usually results in absence of Btk protein

Question 10

What infections are common in individuals with CVID?

Answer 10

RTI/GI; pulmonary disease– bronchiectasis and interstitial lung disease

Question 11

Common non-infectious complications of CVID

Answer 11

Lung disease
Neoplasia (B cell lymphoma, gastric carcinoma) 
Autoimmunity 
GI disease
Liver disease

Question 12

What constitutes a CVID diagnosis?

Answer 12

Low IgG AND low IgA and/or low IgM

Question 13

What is the most common Ab deficiency?

Answer 13

IgA deficiency

Question 14

What constitutes IgA deficiency diagnosis?

Answer 14

Low IgA – normal IgG and IgM

Question 15

What causes false positive results with IgA deficiency?

Answer 15

Heterophile antibodies: antibodies that recognize an antigen different than the antigen that originally induced the Ab response

Question 16

What is the main clinical finding in individuals with specific antibody deficiency?

Answer 16

abnormal specific antibody response to immunization (especially PS antigens)

Question 17

What is the pathogenesis of CGD?

Answer 17

An absence of respiratory burst in neutrophils and monocytes – impaired bactericidal killing; defect in NADPH oxidase

Question 18

What is one presentation that should be considered CGD until proven otherwise?

Answer 18

Hepatic abscess without obvious source in young child

Question 19

What is unique about mothers of boys with X-linked CGD?

Answer 19

Random X chromosome inactivation occurs so that 50% of the mother’s neutrophils express normal NADPH oxidase and 50% express the defective NADPH oxidase

Question 20

What are the genetic mutations in LAD-1 and LAD-2?

Answer 20

LAD-1 mutation in common gamma chain

LAD-2 mutation in GDP-fructose transporter which leads to an absence of sialyl LewisX

Question 21

Will leukocyte count be high or low in leukocyte adhesion deficiency?

Answer 21

High – because there will not be any adhered to endothelium

Question 22

How do patients with LAD-1 present?

Answer 22

Recurrent pyogenic infections, delayed umbilical cord detachment, leucocytosis, inability to form pus

Question 23

Those with late complement deficiency are highly susceptible to what bug?

Answer 23

Neisseria

Question 24

What is the most common complement deficiency?

Answer 24

C2, autosomal recessive