PID Flashcards
Common Causes of SECONDARY immune deficiency
Infection, malnutrition, malignancy, Immunosuppresant drugs, metabolic disorders, loss of protein (usually kidney disease), collagen vascular disease
When should you be suspicious of presence of primary immune deficiency? (4)
- Repetitive infection
- Odd organisms
- Odd patterns and early onset of autoimmune disease
Name 2 Neutrophil deficiency PIDs.
Chronic Granulomatous Disease, Leukocyte Adhesion Deficiency
Clinical Features of Neutrophil Deficiency diseases. (5)
early onset Catalase + organisms peridontal disease ABSCESS poor healing/lack of neutrophils (pus)
Neutrophil Defect initial and secondary dx methods
Initial: CBC with absolute neutrophil count; Oxidative burst testing
Secondary: Chemotaxis testing; antineutrophil antibodies
Genetic Basis of Leukocyte Adhesion Deficiency (LAD) types 1 and 2?
LAD1-mutation on the LFA/MAC family of integrins on leukocytes
LAD2-mutation on Sialyl Lewisx (selectin binder) on leukocytes (autosomal recessive)
Process of Leukocyte adhesion and migration.
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
Clinical features of Leukocyte Adhesion Deficiency (5)
Diagnosis method
Treatment
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)
Complement Deficiency
-Age of onset
any age. Usually late teens for late complement deficiency
Subtypes of Complement Deficiency.
Disease associated/Clinical presentation
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
Complement deficiency (diagnostic method initial and secondary)
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
Chronic Granulomatous Disease
- genetic mutation; mode of inheritance
- Age of Onset
- Genetic mutation of NADPH oxidase–>no oxidative burst in neutrophils
- 2 years old
Chronic Granulomatous Disease
- Clinical features (6)
- bacterias (general; 8 specific)
- pneumonia (70%), adenopathy and abscess (40-50%), LIVER ABSCESS, sepsis, osteomyelitis–WITH GRANULOMAS
- Catalase +: Staph aureus, aspergillus, nocardia, Burkholderia, Klebsiella, Serratia, Candida
Chronic Granulomatous Disease
- Diagnosis method
- Treatments
-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)
Antibody/B cell deficiency subtypes (4)
B cell/ab deficiency is most common.
Agammaglobulinemia (XLA), Common variable immune deficiency, Specific Ab deficiency, IgA deficiency,
General clinical features and age of onset for Antibody/B cell deficiencies
-onset usually during year 1 or 2. CVID is ANY time.
-Clinical features: recurrent sinopulmonary infections (especially encapsulated organisms)
Enteroviral meningitis; GI infection
Antibody/B cell deficiencies-Diagnostic methods
Initial: Quantitative Immunoglobulins (IgG, A, M, E)
test for ANTIBODY TITER for vaccinations
Secondary; Flow cytometry for B cells.
XLA
Clinical features: sx, specific infections
Onset
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)
XLA
Genetic basis
Diagnosis
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)
Common Variable Immune Deficiency (CVID)
Onset
Common clinical features (5)
Common causes of death (3)
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
CVID
Diagnosis
Decreased IgG AND low IgA or IgM.
-Make sure to exclude XLA and secondary causes
IgA deficiency
Common infections
IgA, IgG, IgM, T cells…what’s nl and what’s not.
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.
IgA Deficiency- Treatment…what should you not do and why?
IVIG, the patients are generally a symptomatic and are immunologically normal
How can IgA deficiency and heterophile antibodies cause false negatives and false positives
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.
