Immunodeficiencies

Question 1

X-linked (Bruton) Agammaglobinemia

Answer 1

B-cell

• BTK (tyrosine kinase), u-hc, Iga, BLNK
• X-linked
• No B-cell maturation (increased pro-B-cells)
• Rec. bact/enterovirus/giardia after 6mo
• No peripheral B-cells, Decreased Ig (all), absent/scanty LN’s and tonsils
• Avoid live vaccines

Question 2

Selective IgA deficiency

Answer 2

B-cell

• Unknown (most common primary ID)
• Asymptomatic (most)
• Airway and GI
• Autoimmune
• Atopy
• Anaphylaxis with IgA containing blood products
• Associated with celiac disease

Question 3

Common variable immunodeficiency

Answer 3

B-cell

• Many causes
• Defective B-cell differentiation
• Acquired in 20s-30s
• Autoimmune
• Bronchiectasis, Lymphoma, Sinopulmonary infections
• Decreased plasma cells and Ig’s
• Low to normal B-cells

Question 4

Thymic aplasia (DiGeorge Syndrome)

Answer 4

T-cell

• 22q11 del (failed 3rd/4th pouches)
• Absent thymus and parathyroid
• Tetany, rec. viral/fungal, conotruncal abnormalities (TOF, TA)
• Decreased T-cells, TRECs, PTH, Ca
• Absent thymic shadow (CXR)

Question 5

IL-12 receptor deficiency

Answer 5

T-cell

• Decreased Th1 response
• AR
• Disseminated mycobacterial and fungal (possible post-BCG vaccine)
• Decreased IFN-y

Question 6

AD hyper-IgE syndrome (Job syndrome)

Answer 6

T-cell

• STAT3 mutation (decreased Th17)
• Impaired recruitment if neutrophils to site of infect
• FATED (coarse Facies, cold (noninflammed) staph. Accesses, primary Teeth, hyper-IgE, Dermatological (eczema), bone fractures
• Increased IgE, decreased IFN-y, eosinophilia

Question 7

Chronic mucocutaneous candidiasis

Answer 7

T-cell

• Many causes
• Noninvasive candida albicans of skin/mucosa
• T-cells don’t respond to candida Ag

Question 8

Transient Hypogammaglobinemia of Infancy

Answer 8

B-cell

• IgM, IgG or IgA greater than 2SD below mean
• Normal Ab production to polio and HA vaccines
• intact cellular immunity
• rec. non-serious infections

Question 9

IFN-y receptor def

Answer 9

T-cell

- Disseminated TB early in life (inc. from BCG)

Question 10

Severe Combined Immunodeficiency (SCID)

Answer 10

B and T cell

• IL-2R gamma chain (X-linked), ADA (AR), MHC-II def, JAK3 (AR), IL-7R alpha chain, IKBKB
• Failure to thrive, chronic diarrhea, thrush
• Rec. viral, bact, fungal, protozoal
• Vaccine susceptible
• Decreased TRECs
• Absent thymic shadow, germinal centres, T-cells
• Rx: BM transplant, isolation, gene Tx

Question 11

Ataxia-telangiectasia

Answer 11

B and T cell

• ATM gene
• Failed ds break repair (DNA) causing cell cycle arrest
• Ataxia (cerebellar), spider Angiomas, IgA def.
• Increased AFP
• Decreased IgA, IgG, IgE
• Lymphopenia and cerebellar atrophy

Question 12

Hyper-IgM syndrome

Answer 12

B and T cell

• Defective: CD40L (XR), CD40 (AR)
• Class switching defect
• Severe pyogenic infections early in life
• Opportunistic infections: Pneumocystis, Cryptosporidium, CMV
• Increased IgM
• Decreased IgG, IgA, IgE

Question 13

Wiskott-Aldrich syndrome

Answer 13

B and T cell

• WAS gene (XR)
• T-cells unable to reorganize actin cytoskeleton (necessary for APC - Tcell synapse)
• WATER (Wiskott-Aldrich: Thrombocytopenic purpura, Eczema, Reccurent infections)
• Increased risk of autoimmune and malignancy
• Decreased to normal IgG, IgM
• Increased IgE, IgA
• Fewer and smaller platelets

Question 14

Leukocyte adhesion deficiency (type 1)

Answer 14

Phagocyte

• Defect in LFA-1 integrin (CD18)
• Impaired migration and chemotaxis
• Autosomal recessive
• Rec. bacterial skin and mucosa infections
• No pus formation
• Impaired wound healing
• Delayed separation of umbilical cord (>30days)
• Increased neutrophils (absent at infection site)

Question 15

Leukocyte adhesion deficiency (type 2)

Answer 15

Phagocyte

• RARE, E-selectin ligands (Sialyl-Lewis X or CD15s) absent (no rolling)
• E-selectin contains fucose: if defect with de novo give oral fucose, if defect with fucose transport to golgi, oral does nothing)
• mental retard, short, distinctive facies

Question 16

Chediak-Higashi syndrome

Answer 16

Phagocyte

• Defect: lysosomal trafficking regulator gene (LYST) [AR]
• Microtubule dysfnc in phagosome-lysosome fusion
• Rec. pyogenic infections w/ staph and strep
• Partial albinism
• Peripheral neuropathy
• Progressive neurodegeneration (+ vision)
• Infiltrative lymphohistiocytosis
• Giant granules in granulocytes and platelets
• Pancytopenia, mild coagulation defects, neutropenia

Question 17

Chronic Granulomatous disease

Answer 17

Phagocyte

• NADPH oxidase defect (XR most common)
• Susceptible to catalase positive (Need PLACESS: Nocardia, Pseudomonas, Listeria, Aspergillus, Candida, E. coli, S. aureus, Serratia)
• Acne, gingivitis, massive LAD, 50% have chronic gut inflammation similar to Chron’s
• Abnormal dihydrorhodamine (flow cytometry) test
• Nitroblue tetrazolium dye reduction test is negative (colourless)

Question 18

MPO deficiency

Answer 18

Phagocyte

• Most asymptomatic
• increased candida infection
• NBT test positive (blue)