Dr. Schurr -- Genetic Predisposition to Infections

Question 1

4 methods of inheritance of primary immunodeficiencies

Answer 1

• X-linked dominant
• X-linked recessive
• Autosomal dominant
• Autosomal recessive

Question 2

4 relatively common primary immunodeficiencies starting from most common

Answer 2

• Selective IgA immunodeficiency
• Common variable immunodeficiency
• Severe combined immunodeficiency
• Chronic granulomatous disease

Question 3

9 conditions that IgA deficiency is associated with

Answer 3

• Chronic lung disease
• Atopy
• Rheumatoid arthritis
• Lupus
• Sjogren’s
• Diabetes
• Pernicious anemia
• Hemlytic anemia
• Autoimmune hepatitis

Question 4

When may complications arise in IgA deficiency?

Answer 4

• Blood transfusion
• IV Ig treatment

Due to natural absence of IgA antibodies

Question 5

2 identified mutations responsible for IgA deficiency and what other condition are they involved in?

Answer 5

• MSH5 (HLA region)
• TNFRSF13B (chromosome 17)

Also involved in common variable immunodeficiency (CVID)

NOTE: Only explains a small proportion of sIAD

Question 6

Define hypogammaglobulinemia

Answer 6

Marked reduction in serum IgG and IgA

IgM reduced in approximately 50% of patients

Question 7

8 conditions associated with CVID

Answer 7

• Recurrent sinopulmonary infections
• Chronic enterovirus
• Arthritis
• Giardiasis
• Increased autoimmune disease
• Lympho-proliferative disease
• Gastric cancers
• lymphoma

Question 8

Treatment for CVID

Answer 8

IVIG (but pay attention to sIAD)

Question 9

6 examples of pathogens that often cause recurrent infections in those with chronic granulomatous disease

Answer 9

Catalase positive pathogens:

• Staph aureus
• Burkholderia cepacia
• Serratia marcescens
• Nocardia
• Aspergillus
• M. tuberculosis

Question 10

Pathophysiology of chronic granulomatous disease

Answer 10

Non-functional NADPH oxidase, a key enzyme in immune defense against pathogens

Question 11

Gene commonly involved in chronic granulomatous disease

Answer 11

Mutations in the X chromosome CYBB gene encoding gp91phox protein (70%)

Question 12

Treatment for chronic granulomatous disease

Answer 12

Preventive antibiotic treatment

Question 13

Cure for chronic granulomatous disease

Answer 13

Gene therapy

Question 14

Mendelian Susceptibility to Mycobacterial Diseases (MSMD): IFNgammaR1/2 deficiency effects (4)

Answer 14

• Severe outcome
• Early onset BCG + EnvMyc
  
  • Mainly mycobacteria
• Prognosis poor

Question 15

MSMD: IL12B deficiency effects (4)

Answer 15

• Less severe outcome
• BCGosis (100% if exposed)
• Salmonella common
• Prognosis good

Question 16

MSMD: IL12RB1 deficiency effects (6)

Answer 16

• Highly variable penetrance
• Mendelian TB
• Salmonellosis common
• Few relapses
• Primary immunity to mycobacterium
• Prognosis good

Question 17

Treatment for IL12RB1 deficiency in MSMD

Answer 17

Antibiotics plus recombinant IFNgamma

Question 18

Major gene that protects against P. falciparum and the disorder it causes

Answer 18

HbAS (sickle cell)

Question 19

Major gene that protects against P. vivax and the disorder it causes

Answer 19

DARC (Duffy blood group)

Question 20

Major gene that protects against Norovirus and the disorder it causes

Answer 20

FUT2 (no secretor mutation)

Question 21

Major gene that protects against HIV and the disorder it causes

Answer 21

CCR5 (32 bp deletion)

Question 22

Major gene that protects against Creutzfild-Jakob and the disorder it causes

Answer 22

PrP (codon 129 valine hz)

Question 23

Major gene that protects against cerebral malaria and the disorder it causes

Answer 23

Band 3 (ovalocytosis)