DS Immunodeficiencies

Question 1

• One of the MC; Caucasians
• Recurrent sinopulmonary infxn
• Autoimmune, GI, endocrine disorders
• Can progress to CVID

Answer 1

Selective IgA deficiency

Question 2

• Male kids
• no/small amounts of B cells and no/little serum Ig
• nodes small, tonsils absent
• expressed around 6m after maternal IgG exhausted
• recurrent bac infxn (esp encapsulated)
• B-, T+

Answer 2

XLA

Question 3

• X-linked
• genetic defect in CD40L on helper T cells
• recurrent bacterial infxn (OM, pneumonia, septicemia)
• some may have opportunistic viral or fungal infxn d/t CD40L defect
• B+, T+

Answer 3

Hyper IgM syndrome 1 (CD40L def)
no CD40L > no allowing for class switching and can also have defect in cell immunity (opportunistic infxn d/t macrophages and DCs being affected)

Question 4

• AR
• lymphoid hyperplasia common
• defect in activation-induced cytidine deaminase gene in B cells
• recurrent bac infxn (OM, pneumonia, septicemia)
• B+, T+

Answer 4

Hyper IgM syndrome 2 (AID deficiency)

Question 5

• onset in 2,3 decade
• heterogenous group of disorders (recurrent OM or sinopulmonary infxn, persistent diarrhea)
• slow decline in Ig > usually low IgG, IgA
• may have hx of poor response to vaccines
• increased incidence of autoimmune disease, leukemia, lymphoma
• B+, T+

Answer 5

CVID/adult onset agammaglobulinemia

Question 6

• congenital defect in organs deriving from 3rd and 4th pharyngeal pouches
• T cell deficiency varies depending on how much thymus is present > can get increased infxn
• NK+, B+, T-, no class switching in most severe cases
• often triad of hypocalcemia, diminished T function, congenital heart disease

Answer 6

DiGeorge (congenital thymic aplasia)

Question 7

• complete syndrome w/ triad of eczema, recurrent pyogenic infxn, thrombocytopenia (often unusually small)
• classic triad of bleeding, eczema, recurrent infxn
• XL, often diagnosed soon after birth
• B+, T-, low IgM, High IgA, IgE

Answer 7

Wiskott-Aldrich syndrome

Question 8

• recurrent infxn early in life, FTT, chronic diarrhea
• Therapy usually stem cell transplant
• usually fatal w/i first 2y unless immune system rescued with bone marrow transplant

Answer 8

SCID

Question 9

• X-Linked gene encoding common gamma chain for various cytokine receptors (IL-2, 4, 7, 9, 15, 21)
• B+, T-, NK-, no class switching

Answer 9

XL SCID

Question 10

Enzymes involved in purine metabolism and deficiency leads to toxic buildup of dATP and dGTP, esp in proliferating lymphocytes

Answer 10

adenosine deaminase deficiency (ADA) and purine nucleoside phosphorylase deficiency (PNP) in SCID

Question 11

ADA deficiency is B, T, NK

Answer 11

all negative

Question 12

PNP deficiency is B, T, NK

Answer 12

B+, low T and NK

Question 13

enzymes responsible for somatic recombination events during B and T cell development
-B-, T-, NK+

Answer 13

RAG1/2 deficiency in SCID

Question 14

• opportunistic infxn with severe consequences > abscess formation (skin and other organs), HSM, LAD, chronic draining lymph nodes, and chronic infected ulcerations and granuloma formation
• avg onset is 2yo
• MC form is XL

Answer 14

CGD

Question 15

-recurrent attacks of edema of SC and submucosal tissues with typical attacks lasting 1-3 days w/o serious effect (if edema in URT > asphyxiation, if in GI > abd pain, cramps, severe vomiting)

Answer 15

Hereditary angioedema

Question 16

complement component deficiencies

Answer 16

• serious infxn and high incidence of autoimmune disease (esp SLE-like and GN with C1, 2, 4)
• recurrent bac infxn d/t def opsonization and complement-assisted antibody production (C3)
• MAC (C5-9) > Neisseria
• meningitis pt should be evaluated for complement def

Question 17

• absolute neutrophil count below 1500/microliter
• several genetic defects of varying severity of AD, AR, or XL inheritance
• oropharyngeal problems, OM, resp infxn, cellulitis and skin infxn
• tx with G-CSF (filgrastim)

Answer 17

severe congenital neutropenia

Question 18

complications of G-CSF tx

Answer 18

Malignancy and osteopenia

Question 19

HAE deficiency

Answer 19

-deficiency in complement control protein (C1 inhibitor - serine protease inhibitor) > regulates complement activation and production of inflammatory kinins > excess bradykinin production

Question 20

CGD defect

Answer 20

-defect in NADPH oxidase enzymes in phagocytic cells > diminished resp burst > defect in intracell killing of microbes

Question 21

Infxn in SCID

Answer 21

Candida, pneumocystitis jirovecii, rotavirus and other bac infxn in GI tract, fatal infxn from live organism vaccines

Question 22

Wiskott-Aldrich defect

Answer 22

WASP defect > signaling and actin cytoskeletal function

Question 23

DiGeorge

Answer 23

CATCH-22
Cardiac defects
Abnormal facies
Thymic hypoplasia
Cleft palate
Hypocalcemia
22q11 deletion