Primary Immunodeficiencies

Question 1

What defect would you want to screen for with recurrent skin abscesses/ or fungal infections

Answer 1

Phagocyte defect

Question 2

MyD88 deficiency

Answer 2

Impaired signaling for all TLRs except TLR3
Recurrent pyogenic bacteria infection
Patients lack fevers and lack elevated levels of ESR/CRP during infection
Low TNF-a, IL-1, IL-6 during infection

Question 3

DiGeorge syndrome

Answer 3

T-, B+, NK+
T-cell deficiency
Hypoplastic thymus, cardiac abnormalities, hypocalcemia

Question 4

HIGM

Answer 4

High IgM, low IgG/IgA, T+, B+, NK+

Normal levels of peripheral B cells, low CD27+ memory B cells

Question 5

Transient Hypogammaglobulinemia of Infancy

Answer 5

Low IgG/IgA, IgM is normal or low
Intrinsic IgG production is delayed for up to 36 months
Increased susceptibility to sinopulmonary infection

Question 6

C2 deficiency

Answer 6

Most common complement deficiency in caucasion

Found in young kids with recurrent streptococcus pneumoniae

Question 7

Paroxysmal nocturnal hemoglobinuria

Answer 7

GPI deficiency
DAF and CD59 not linked to membrane
Increased RBC susceptibility to hemolysis

Question 8

PNP deficiency

Answer 8

Purine nucleoside phosphorylase deficiency
T-, B-, NK+
Accumulation of intracellular dGTP
Early neurological abnormalities
Common to have associated AI disorders including hemolytic anemia, thyroid disease, arthritis, lupus
HSCT is treatment

Question 9

Agammaglobulinemia

Answer 9

B cell development is arrested at the pre-B cell stage
Circulating B cells are absent or low in number
T+, B-, NK+

Question 10

CD3 deficiency

Answer 10

T-, B+, NK+, Low IgG, IgA
Form of SCID
Lymphopenia, decreased T cells
Specific Ab response is decreased
Failure to thrive, opportunistic inf, diarrhea

Question 11

NK deficiency- NKD

Answer 11

Classical NKD= Absence of NK cells (GATA2 deficiency)
Functional NKD= Presence of NK cells with defective activity (perforin deficiency)
Recurrent viral infections

Question 12

Chronic granulomatous disease CGD

Answer 12

Phagocytic disorder, tendency to form granulomas
Deficiency of NADPH oxidase in phagocytes
Cannot generate superoxide anion
Defective elimination of extracellular pathogens
Recurrent inf with catalase positive organisms (staph)

Question 13

Th17 deficiency

Answer 13

Susceptible to chronic mucocutaneous candidiasis

Mutations in IL-17/IL-17R, TFs- STAT1, STAT3 or AIRE

Question 14

CD40L deficiency

Answer 14

Responsible for 2/3 of HIGM cases
Unable to class switch or activate B cells, no B cell differentiation

Question 15

SCID

Answer 15

Low IgA, IgG, IgM
Severe lymphopenia
Severe opportunistic infections
At risk of abortion due to inability to reject maternal T cells
Avoid all live viral vaccines

Question 16

ADA deficiency

Answer 16

Second most common cause of SCID

Leads to accumulation of toxins for lymphocytes metabolic by-products deoxyadenosine

Question 17

ALPS

Answer 17

Defects in Fas, FasL, Caspase-8 or 10 results in abrogated formation of death-inducing signaling complex DISC and resistance of effector T cells to apoptosis

Question 18

Bare lymphocyte syndrome II

Answer 18

CD4-, CD8+, B+, NK+
No MHC II expression, deficient CD4 cells
Respiratory/GI/UT infections, early death

Question 19

Common variable immune deficiency CVID

Answer 19

Defect in Ab production, B-/+, T+, NK+
Number of circulating B cells is low or normal
B cells cannot differentiate into plasma cells
Recurrent pyogenic sinopulmonary infections

Question 20

IL-7R alpha chain deficiency

Answer 20

T-, B+, NK+, IgA/IgG low
Ig levels are low/absent due to absence of T cell costimulatory signaling
Candidiasis, diarrhea, pneumocystis jiroveci pneumonia, severe viral infections

Question 21

X-linked BTK deficiency

Answer 21

Defect in rearrangement of Ig heavy chains
IgA, IgG, IgM are absent or very low
B-, T+, NK+

Question 22

Isolated IgG deficiency

Answer 22

Decreased concentration of one or more IgG subclass
Usually asymptomatic, can be associated with recurrent viral/bacterial infections- usually respiratory
B+, T+, NK+

Question 23

What are you looking for after a failed DTH skin test

Answer 23

T cell defects

Question 24

Factor H deficiency

Answer 24

Associated with atypical hemolytic uremic syndrome or glomerulonephritis

Question 25

Leukocyte adhesion deficiency LAD

Answer 25

Neutrophilia (2x normal # even if not currently infected)
Neutrophils are unable to aggregate
Recurrent infection of oral/genital mucosa, intestine, respiratory tract
Few neutrophils able to be transported to sites of inflammation- slow healing, dysplastic scars

Question 26

Jak3 deficiency

Answer 26

SCID caused by mutation in Jak3
Causes defect in IL-2 receptor signaling
T-, B+, NK-

Question 27

LAD I-III

Answer 27

LAD I- B2 integrin gene mutation- no B2 integrin
LAD II- impaired adhesive function of PSGL-1
LAD III- impaired signaling of B2 integrin

Question 28

RAG1/RAG2 deficient SCID phenotype

Answer 28

T-
B-
NK+/-
Leaky RAG1/RAG2 defect can give rise to atypical form of SCID known as Omenn syndrome (high IgE)

Question 29

ADA deficient SCID phenotype

Answer 29

T-
B-
NK-

Question 30

Wiskott-Aldrich syndrome WAS

Answer 30

Low IgM, normal IgG, elevated IgA/IgE, T-, B+, NK+
T cell lymphopenia, decreased NK cytotoxicity
Recurrent encapsulated bacterial infections
Viral infection, PJPneumonia/candida
Thrombocytopenia, eczema, cellular/humoral immunodeficiency, AI disease

Question 31

MHC I deficiency (BLS I?)

Answer 31

Mutation in TAP1 protein
CD8+ cells deficient- recurring viral infections
Normal DTH, Ab production, CD4 cells

Question 32

Common y chain deficiency (yc or IL-2Ry)

Answer 32

Most common form of SCID, T-, B+, NK-
Low IgG, IgA
IL-2Ry deficient because y chain mutation
No functional B cells since T cells are unable to help
Failure to thrive, thrush, opportunistic infection, diarrhea

Question 33

Defect in IL-12/IFN-y pathway

Answer 33

IL-12 produced by DCs & MOs stimulates IFN-y release by T/NK cells
Increased susceptibility to nontuberculous mycobacteria
IL-12 essential for differentiation of naïve Th1 cells
Susceptibility to intracellular pathogens and fungal infection
Defective formation of IL-17 producing Th17 cells (hence the fungal infections)

Question 34

IgA deficiency

Answer 34

B+, T+, NK+
Recurrent infections with encapsulated bacteria
Many times IgM can compensate for loss of IgA
Often develop autoimmune disease & allergy
Possible development of non-IgE mediated anaphylaxis in response to IVIG transfusion

Question 35

What defect would you screen for in bacteremia or meningitis with encapsulated bacteria

Answer 35

Complement deficiency

Question 36

IPEX

Answer 36

Self reactive T effector cells are not inhibited because of a mutation in FOXP3 results in loss of inhibition by Treg cells

Question 37

Artemis deficiency

Answer 37

Rare radiosensitive SCID
T-, B-, NK+
Candidiasis, pneumocystis jiroveci pneumonia
Increased risk for lymphomas

Question 38

Hereditary angioedema

Answer 38

C1 INH deficiency
Swelling of extremities/lips/face/larynx
Production of bradykinin increased because kallikrein is not inhibited

Question 39

Primary C1/C4 deficiency

Answer 39

Linked to development of SLE or RA

Large immune complexes are not cleared and form deposits in tissues causing inflammation

Question 40

G6PD deficiency

Answer 40

Associated with anemia
Lack of substrate for NADPH
Same manifestation as CGD- granulomas

Question 41

Chediak-Higashi syndrome

Answer 41

Wheelchair bound
Abnormal giant neutrophil granules, defective chemotaxis/degranulation
Response to infection- blunted neutrophilia due to delayed diapedesis
Partial albinism, no NK activity