PID

Question 0

Common Causes of SECONDARY immune deficiency

Answer 0

Infection, malnutrition, malignancy, Immunosuppresant drugs, metabolic disorders, loss of protein (usually kidney disease), collagen vascular disease

Question 1

When should you be suspicious of presence of primary immune deficiency? (4)

Answer 1

• Repetitive infection
• Odd organisms
• Odd patterns and early onset of autoimmune disease

Question 4

Name 2 Neutrophil deficiency PIDs.

Answer 4

Chronic Granulomatous Disease, Leukocyte Adhesion Deficiency

Question 5

Clinical Features of Neutrophil Deficiency diseases. (5)

Answer 5

early onset 
Catalase + organisms
peridontal disease
ABSCESS
poor healing/lack of neutrophils (pus)

Question 6

Neutrophil Defect initial and secondary dx methods

Answer 6

Initial: CBC with absolute neutrophil count; Oxidative burst testing
Secondary: Chemotaxis testing; antineutrophil antibodies

Question 8

Genetic Basis of Leukocyte Adhesion Deficiency (LAD) types 1 and 2?

Answer 8

LAD1-mutation on the LFA/MAC family of integrins on leukocytes
LAD2-mutation on Sialyl Lewisx (selectin binder) on leukocytes (autosomal recessive)

Question 9

Process of Leukocyte adhesion and migration.

Answer 9

Chemotactic factors and vasodilation–>marginalization–>E selectin and P selectin expressed on endothelial cells loosely bind Sialyl Lewisx on leukocytes.–>expression of integrins (with common CD18) on leukocytes binds ICAMs on endothelial cells.–>expression of PECAM leads to transendothelial migration–>chemotactic factors lead cells to site of infection

Question 10

Clinical features of Leukocyte Adhesion Deficiency (5)
Diagnosis method
Treatment

Answer 10

poor wound healing, NO PUS, recurrent pyogenic infections, leukocytosis, delayed umbilical cord detachment.

• induce integrin upregulation and do flowcytometry
• Aggressive tx of the infections…bone marrow transplant (cure)

Question 11

Complement Deficiency

-Age of onset

Answer 11

any age. Usually late teens for late complement deficiency

Question 12

Subtypes of Complement Deficiency.

Disease associated/Clinical presentation

Answer 12

Early Complement Deficiency: C2, C4; associated with SLE (and other collagen vascular disease); recurrent bacteremia such as Peumococcus, H. Influenza, Enterobacter

Late Complement Deficiency: C5-C9 Usually first infection around 17. Recurrent Neisseria infections.

C3 deficiency:: recurrent pyogeneic bacterial infections

Question 13

Complement deficiency (diagnostic method initial and secondary)

Answer 13

Do CH50 for classical pathway.

Secondarily. If positive… do individual testing
If more than 1 complement is deficient…consider protein loss rather than PID
Try AH50 to test for alternative pathway

Question 14

Chronic Granulomatous Disease

• genetic mutation; mode of inheritance
• Age of Onset

Answer 14

• Genetic mutation of NADPH oxidase–>no oxidative burst in neutrophils
• 2 years old

Question 15

Chronic Granulomatous Disease

• Clinical features (6)
• bacterias (general; 8 specific)

Answer 15

• pneumonia (70%), adenopathy and abscess (40-50%), LIVER ABSCESS, sepsis, osteomyelitis–WITH GRANULOMAS
• Catalase +: Staph aureus, aspergillus, nocardia, Burkholderia, Klebsiella, Serratia, Candida

Question 16

Chronic Granulomatous Disease

• Diagnosis method
• Treatments

Answer 16

-Dihydrorhodamine test- (preferred test)- inject dye and induce oxidative burst- view the change using flow cytometry
Or Nitroblue Tetrazolium test
-treatments: TM-Sulfa for Staph prophylaxis; Itraconazole for fungal tx/prophylaxis; Use corticosteroids for tx of granulomas

Bone marrow transplant (cure)

Question 17

Antibody/B cell deficiency subtypes (4)

Answer 17

B cell/ab deficiency is most common.

Agammaglobulinemia (XLA), Common variable immune deficiency, Specific Ab deficiency, IgA deficiency,

Question 18

General clinical features and age of onset for Antibody/B cell deficiencies

Answer 18

-onset usually during year 1 or 2. CVID is ANY time.
-Clinical features: recurrent sinopulmonary infections (especially encapsulated organisms)
Enteroviral meningitis; GI infection

Question 19

Antibody/B cell deficiencies-Diagnostic methods

Answer 19

Initial: Quantitative Immunoglobulins (IgG, A, M, E)
test for ANTIBODY TITER for vaccinations

Secondary; Flow cytometry for B cells.

Question 20

XLA
Clinical features: sx, specific infections
Onset

Answer 20

onset in infancy/early childhood
clinical features: recurrent otitis, sinusitis, pneumonia
-susceptible to encapsulated bacteria (s. pneumonia, H. influenza, MYCOPLASMA) and enteroviral infections (vaccine related polio)

Question 21

XLA
Genetic basis
Diagnosis

Answer 21

Bruton’s Tyrosine Kinase (Btk) mutation..no B cell differentiation.

BCR stimulation–> signal transduction via ITAM, then syk, then to BTK (as a survival signal) to pass phosphorylation to PLCgamma2.

Dx: flow cytometry for btk protein (early dx important to avoid bronchiectasis)

Question 22

Common Variable Immune Deficiency (CVID)
Onset
Common clinical features (5)
Common causes of death (3)

Answer 22

Onset-any age (usually greater than 2 years)
Pulmonary disease-bronchiectasis; interstitial disease
GI infections
Liver disease
Malignancies- lymphomas; gastric carcinoma
Autoimmunity-cytopenia

Pulmonary disease, cancer complications, liver disease

Question 23

CVID

Diagnosis

Answer 23

Decreased IgG AND low IgA or IgM.

-Make sure to exclude XLA and secondary causes

Question 24

IgA deficiency
Common infections
IgA, IgG, IgM, T cells…what’s nl and what’s not.

Answer 24

Common infections: sinopulmonary infections, GI infections (Giardia), and autoimmune processes (Celiac disease)… mostly however are phenotypically nl

IgA very low. IgG/M/T cells are all nl.

Question 25

IgA Deficiency- Treatment…what should you not do and why?

Answer 25

IVIG, the patients are generally a symptomatic and are immunologically normal

Question 26

How can IgA deficiency and heterophile antibodies cause false negatives and false positives

Answer 26

False negative: You don’t see an IgA response, so you think the disease/infection is not present

False positive: nonspecific heterophile antibodies bind to other proteins. (false positive preg test)

-Heterophile antibodies also frequently bind Igs of other species.

Question 27

Specific Antibody Deficiency
IgG,A,M,Tcell function?
most common abnormal specific antibody response?
How can this be diagnosed

Answer 27

All IgG, A, M, T cell functions are normal!

• abnl response to polysaccharide ag.
• measure antibody response pre and 4 weeks post vaccination with PS.

Question 28

What MUST you do to diagnose infections

Answer 28

culture, PCR, or other direct method. CANNOT do serological assays for pts with ab deficiencies.

Question 29

Name 2 T cell or Combined immune deficient syndromes.

Answer 29

SCID; DiGeorge syndrome (22q11.2)

Question 30

most severe PID?

Answer 30

Combined B and T cell deficiency (SCID)

Question 31

T cell deficiency/Combined defect workup

Answer 31

Lymphocyte enumeration via Flow cytometry.

CANNOT just do all lymphocyte count…MUST account for numbers of NK, T, B, memory T, and Naive T cells.
-Quantify immunoglobulins; and T cell proliferation test.

Question 32

Severe combined immunodeficiency (SCID)

• most common mode of inheritance.
• Molecular mutation

Answer 32

Xlinked.
common gamma chain mutation of IL2 receptor (which is the signal component is also shared by other interleukin receptors…IL4, IL7, IL15, IL21)
-NO T CELLS NO NK CELLS; B cells present but nonfunctional.

Question 33

SCID
Onset
symptoms and common infections

Answer 33

infancy. (however asymptomatic at birth)
- pathogenic and opportunistic infections. Pneumonia (p. jirovecii), otitis media, thrush, intractable diarrhea, failure to thrive.

Question 34

SCID
Diagnosis
Treatment

Answer 34

Screening test: CBC, lymphopenia (s 100% fatal.

Question 35

Screening test for SCID;

What is the result in SCID?

Answer 35

T cell receptor Excision Circles (TRECs)-in naive T cells while making TCR. rtPCR can use to measure TRECS as markers of normal naive T cells.

TRECs are LOW in SCID. any T cells in the infants may be from mom… and they would not have TRECs

Question 36

DiGeorge Syndrome

Genetics

Answer 36

microdeletion mutation 22q11.2 (OFTEN WITH TBX1 gene) –> field defect of 1st to 6th pharyngeal pouches.

1:2,000-4,000 live births

Question 37

DiGeorge Syndrome Clinical Features

Answer 37

CATCH22
Cardiac defects
Abnormal facies
Thymic hypoplasia--therefore often autoimmune (LOW T CELLS)
Cleft palate
Hypocalcemia
22

Question 38

DiGeorge Syndrome
Diagnosis
Cannot use what test?

Answer 38

DNA microarray for CNV (PREFERRED), FISH (sometimes false neg), RT QPCR
Cannot use TREC assay because T cell count is not low enough for that.

Question 39

Features arising from 1st arch and 1-4th pharyngeal pouch

Answer 39

1st arch: maxillary/mandible features
1st pouch: TM
2nd pouch tonsil/thyroid
3rd pouch: thymus; inferior parathyroid
4th pouch: superior parathyroid

Question 40

DiGeorge syndrome: T cell/B cells what’s nl what’s not?
You should test for DiGeorge before doing what?
When should you test?

Answer 40

T cell count is very low
B cell count is low–May require IVIG–bc B cell function is dependent on CD4 Tcells.

• test before giving live attenuated vaccines.
• all infants with heart defects or unexplained lymphopenia should be tested.