Primary Immunodeficiency

Question 1

What are the lab findings of DIGEORGE SYNDROME (Include T cell count, Ca2+ level)

Answer 1

1. LOW T-Cell count (Lack of thymus)

2. HYPOCALCEMIA (Lack of parathyroids)

Question 2

What is the genetic mechanism of DIGEORGE SYNDROME?

Answer 2

22q11 microdeletion

Question 3

What is deficient in SEVERE COMBINED IMMUNODEFICIENCY SYNDROME?

Answer 3

Defective B cell and T cell mediated responses

Question 4

What are the 3 etiologies of SCID?

Answer 4

1. ADENOSINE DEAMINASE DEFICIENCY (ADA Deficiency) - Buildup of adenosine and deoxyadenosine = toxic to lymphocytes
2. MHC CLASS II DEFICIENCY
3. CYTOKINE RECEPTOR DEFECT

Question 5

What are the two treatments of SCID?

Answer 5

1. TEMPORARY Sterile isolation (bubble baby)

2. HSC (stem cell) Tx - Able to generate B and T cells again

Question 6

What is the inheritance pattern of BRUTON AGGAMGLOBULINEMIA? What is the mutation in?

Answer 6

X-linked recessive - Also called X-LINKED AGAMMAGLOBULINEMIA

Mutation in BRUTON TYROSINE KINASE - Enzyme required to mature naive B cells into plasma B cells

Question 7

What 3 types of infections are BRUTON AGAMMAGLOBULINEMIA pts (any pt lacking plasma B cell response) susceptible to?

Answer 7

1. BACTERIAL INFECTION (Otitis Media, Sinusitis, Pneumonia)- No IgG to opsonize bacteria
2. ENTEROVIRUS INFECTION - No IgA to protect GI mucosal surfaces attacked by polio, Coxsackie A/B, etc.
3. GIARDIA LAMBIA INFECTION - No IgA to protect GI mucosal surfaces attacked by giardia

Question 8

When does BRUTON AGAMMAGLOBLINEMIA tend to present?

Answer 8

AFTER 6mo of birth

Due to presence of maternal Abs in baby for 6mo after birth

Question 9

Developmental failure of 3rd and 4th pharyngeal pouch. Which primary immunodeficiency am I?

Answer 9

DIGEORGE SYNDROME

Question 10

What is the defect in COMMON VARIABLE IMMUNODEFICIENCY (CVID)?

Answer 10

Defect in helper T or B cells -> Low Ig

Question 11

What infections and disease states are pts with COMMON VARIABLE IMMUNODEFICIENCY susceptible to?

Answer 11

1-3. Same as any pt with DEFECTIVE B CELL RESPONSE: Bacterial, Enterovirus, Giardia Lamblia

4. AUTOIMMUNE DISEASE
5. LYMPHOMA

Question 12

What is the most common IMMUNOGLOBULIN DEFICIENCY?

Answer 12

IgA

Question 13

In pts with HYPER IgM SYNDROME, what are the two possible mutations?

Answer 13

1. CD40Ligand (on Th cell)

2. CD40Receptor (On B cell)

Question 14

What is the inheritance pattern of WISKOTT-ALDRICH SYNDROME? What is the mutation in?

Answer 14

X-linked recessive

WASP - Wiskott-Aldrich Syndrome Protein

Question 15

What is the clinical triad of WISKOTT-ALDRICH SYNDROME?

Answer 15

1. THROMBOCYTOPENIA - Increased risk of bleeding, petechiae, mucosal bleeding
2. ECZEMA - Rash on skin
3. Recurrent infections

Question 16

What is a major cause of death in WISKOTT-ALDRICH SYNDROME?

Answer 16

BLEEDING

Due to THROMBOCYTOPENIA induced by mutation in WASP gene

Question 17

PERIORBITAL ANGIOEDEMA and MUCOSAL ANGIODEMA that is hereditary. Which deficiency am I?

Answer 17

C1 INHIBITOR DEFICIENCY -> Overactivation of C1 -> Overactivation of complement pathway

Question 18

What is the defect in COMMON VARIABLE IMMUNODEFICIENCY (CVID)?

Answer 18

Defect in helper T or B cells -> Low Ig

Question 19

What infections and disease states are pts with COMMON VARIABLE IMMUNODEFICIENCY susceptible to?

Answer 19

1-3. Same as any pt with DEFECTIVE B CELL RESPONSE: Bacterial, Enterovirus, Giardia Lamblia

4. AUTOIMMUNE DISEASE
5. LYMPHOMA

Question 20

What is the most common IMMUNOGLOBULIN DEFICIENCY?

Answer 20

IgA

Question 21

In pts with HYPER IgM SYNDROME, what are the two possible mutations?

Answer 21

1. CD40Ligand (On B cell as an APC)

2. CD40Receptor (On Th cell)

Question 22

What is the inheritance pattern of WISKOTT-ALDRICH SYNDROME? What is the mutation in?

Answer 22

X-linked recessive

WASP - Wiskott-Aldrich Syndrome Protein

Question 23

What is the clinical triad of WISKOTT-ALDRICH SYNDROME?

Answer 23

1. THROMBOCYTOPENIA - Increased risk of bleeding, petechiae, mucosal bleeding
2. ECZEMA - Rash on skin
3. Recurrent infections

Question 24

What is a major cause of death in WISKOTT-ALDRICH SYNDROME?

Answer 24

BLEEDING

Due to THROMBOCYTOPENIA induced by mutation in WASP gene

Question 25

PERIORBITAL ANGIOEDEMA and MUCOSAL ANGIODEMA that is hereditary. Which deficiency am I?

Answer 25

C1 INHIBITOR DEFICIENCY -> Overactivation of C1 -> Overactivation of complement pathway

Question 26

EOSINOPHILIA + ECZEMA + ETERNAL RECURRENT PURULENT INFECTION. Which immunodeficiency or hyper-immunoglobulin syndrome am I?

Answer 26

HYPER IgE SYNDROME (Job’s Syndrome)

3 E’s

Question 27

What is a characteristic physical finding specific to BRUTON’S AGAMMAGLOBULINEMIA, in contrast with other HUMORAL IMMUNITY DEFICIENCIES?

Answer 27

Absence or near absence of tonsils + adenoids

Question 28

What is the difference between HYPER IgM SYNDROME and WALDENSTROM MACROGLOBULINEMIA?

Answer 28

HYPER-IgM (Primary Immunodeficiency): ELEVATED IgM, No class switching - Low IgA, IgE, IgG 
Mechanism: Mutation in CD40L (Th) or CD40 (B cell) 

WALDENSTROM MAGROGLOBULINEMIA (WBC Disorder): ELEVATED IgM, normal levels of other Abs -> Hyperviscosity syndrome (bleeding, blurriness, retinal hemorrhages), Generalized Lymphadenopathy, Elevated protein (M-spike) 
Mechanism: B cell lymphoma with monoclonal IgM production

Question 29

How do differentiate between AGAMMAGLOBULINEMIA and SCID, in context to the humoral deficiency?

Answer 29

BRUTON’S AGAMMAGLOB: LOW plasma B cell #’s, LOW Igs

SCID: In addition to low T cell, low NK cell, you have LOW Igs BUT NORMAL plasma B cells

Question 30

What is the mutation in JOB SYNDROME (HYPER IgE)?

Answer 30

STAT3 mutation