Primary immunodeficiency diseases

What are primary immunodeficiency diseases?

Genetic immune defects

What is the major consequence of primary immunodeficiency diseases?

Recurrent infections

Primary immunodeficiencies increase the risk of what two noninfectious conditions?

Autoimmunity and malignancy

What is the estimated incidence of primary immunodeficiency diseases?

1:2000–1:10000 births

Can primary immunodeficiencies present in adulthood?

Yes

What are the three levels of host defense?

Barriers, innate, adaptive

What causes primary immunodeficiency?

Genetic defect

What causes secondary immunodeficiency?

Acquired insult

When may symptoms of primary immunodeficiency appear?

Birth or later

Recurrent ear infections suggest what disorder category?

Immunodeficiency

Recurrent sinusitis and pneumonia suggest what disorder category?

Immunodeficiency

Persistent candidiasis suggests what disorder category?

Immunodeficiency

Infections with opportunistic pathogens suggest what disorder category?

Immunodeficiency

Malnutrition causes what type of immunodeficiency?

Secondary

Splenectomy causes what type of immunodeficiency?

Secondary

Hematologic malignancies cause what type of immunodeficiency?

Secondary

HIV causes what type of immunodeficiency?

Secondary

Protein-losing enteropathy causes what type of immunodeficiency?

Secondary

What is the inheritance pattern of chronic granulomatous disease?

X-linked or AR

What enzyme system is defective in chronic granulomatous disease?

NADPH oxidase

What is the main defect in chronic granulomatous disease?

Poor respiratory burst

In chronic granulomatous disease, phagocytes can ingest organisms but cannot do what?

Kill them

Chronic granulomatous disease predisposes to infection with what organisms?

Catalase-positive organisms

Which organism commonly infects patients with chronic granulomatous disease?

Staphylococcus aureus

Which fungal organism commonly infects patients with chronic granulomatous disease?

Candida

Which Gram-negative organisms commonly infect patients with chronic granulomatous disease?

Serratia and Klebsiella

What test is abnormal in chronic granulomatous disease?

NBT test

What color do normal cells become in the NBT test?

Blue

What color do abnormal cells become in the NBT test?

Yellow

What cytokine is used to treat chronic granulomatous disease?

IFN-γ

Which membrane protein is commonly defective in X-linked chronic granulomatous disease?

gp91-phox

What enzyme produces hypochlorite in neutrophils?

Myeloperoxidase

What substance is required for bacterial killing by myeloperoxidase?

ClO−

How is bacterial killing affected in myeloperoxidase deficiency?

Slowed

How does the NBT test appear in myeloperoxidase deficiency?

Normal

What is the inheritance pattern of Chediak-Higashi syndrome?

Autosomal recessive

Which gene is mutated in Chediak-Higashi syndrome?

LYST

What is the underlying defect in Chediak-Higashi syndrome?

Defective lysosomal trafficking

What skin finding occurs in Chediak-Higashi syndrome?

Hypopigmentation

What bleeding abnormality occurs in Chediak-Higashi syndrome?

Prolonged bleeding

What type of infections are common in Chediak-Higashi syndrome?

Pyogenic infections

What blood cell abnormality occurs in Chediak-Higashi syndrome?

Neutropenia

Natural killer cell function is abnormal in which disease?

Chediak-Higashi syndrome

What neurologic complication occurs in Chediak-Higashi syndrome?

Peripheral neuropathy

What characteristic finding is seen on blood smear in Chediak-Higashi syndrome?

Giant granules

What is defective in leukocyte adhesion deficiency?

Leukocyte adhesion

Which molecule is deficient in LAD-1?

CD18

Delayed separation of the umbilical cord suggests what disorder?

LAD-1

Failure to form pus is characteristic of what disease?

LAD-1

Which leukocyte function is impaired in LAD?

Chemotaxis

Which process of leukocyte migration is impaired in LAD?

Diapedesis

What is the definitive treatment for leukocyte adhesion deficiency?

Bone marrow transplant

Classical complement pathway deficiencies are associated with what disease?

SLE

MBL deficiency predisposes to infection with what type of bacteria?

Encapsulated bacteria

Alternative pathway deficiencies impair what immune function?

Opsonization

C3 deficiency causes severe infections with what organisms?

Encapsulated bacteria

MAC deficiencies predispose to infection with which genus?

Neisseria

Deficiency of which complement components causes recurrent Neisseria infections?

C5-C9

What protein is deficient in hereditary angioedema?

C1 esterase inhibitor

What is the major manifestation of hereditary angioedema?

Episodic edema

What life-threatening complication may occur in hereditary angioedema?

Laryngeal edema

What does C1 inhibitor normally prevent?

C1 assembly

Lack of C1 inhibitor causes release of which mediator?

Bradykinin

Which androgen is used for prophylaxis of hereditary angioedema?

Danazol

What C1 inhibitor concentrate is used for prophylaxis of hereditary angioedema?

Cinryze

What C1 inhibitor concentrate is used for acute hereditary angioedema?

Berinert

Which kallikrein inhibitor treats acute hereditary angioedema?

Ecallantide

What causes paroxysmal nocturnal hemoglobinuria?

PIGA mutation

What anchor molecule is absent in paroxysmal nocturnal hemoglobinuria?

GPI anchor

What color urine is classically seen in paroxysmal nocturnal hemoglobinuria?

Dark-colored urine in the morning

Paroxysmal nocturnal hemoglobinuria causes what type of anemia?

Hemolytic anemia

What blood cell abnormality accompanies paroxysmal nocturnal hemoglobinuria?

Pancytopenia

What major vascular complication occurs in paroxysmal nocturnal hemoglobinuria?

Thrombosis

Which complement regulatory proteins are absent in paroxysmal nocturnal hemoglobinuria?

CD55 and CD59

What test confirms paroxysmal nocturnal hemoglobinuria?

Flow cytometry

What monoclonal antibody is used to treat paroxysmal nocturnal hemoglobinuria?

Eculizumab

What is the definitive treatment for paroxysmal nocturnal hemoglobinuria?

Bone marrow transplant

What is the underlying defect in X-linked agammaglobulinemia?

BTK mutation

What stage of B-cell development is arrested in Bruton disease?

Pre-B cell

Which enzyme is defective in Bruton agammaglobulinemia?

BTK

What cells are absent in Bruton agammaglobulinemia?

Mature B cells

What happens to plasma cells in Bruton disease?

Absent

How do serum immunoglobulin levels appear in Bruton disease?

All decreased

What type of infections occur in Bruton disease?

Recurrent bacterial infections

At what age does Bruton disease usually present?

Infancy

Which ear infection commonly occurs in Bruton disease?

Otitis media

Which respiratory infections occur in Bruton disease?

Pneumonia and sinusitis

Which encapsulated organism commonly infects Bruton patients?

Streptococcus pneumoniae

Which Gram-negative coccobacillus commonly infects Bruton patients?

Haemophilus influenzae

Which Gram-negative rod may infect Bruton patients?

Pseudomonas

What skin condition may occur in Bruton disease?

Eczema

What CNS infection may occur in Bruton disease?

Meningitis

What gastrointestinal manifestation occurs in Bruton disease?

Bacterial diarrhea

What autoimmune complication may occur in Bruton disease?

Autoimmune disease

What finding is seen on flow cytometry in Bruton disease?

Absent B cells

Which immunoglobulin deficiency is the most common primary immunodeficiency?

Selective IgA deficiency

Selective IgA deficiency results from a defect in what process?

Class switching

What immunoglobulin is decreased in selective IgA deficiency?

IgA

Which body systems are commonly infected in IgA deficiency?

Sinus and lungs

Which mucosal infections are common in IgA deficiency?

GI and nasopharyngeal