First Aid, Chapter 8, Immunologic Disorders, Antibody Deficiencies Flashcards
When should antibody deficiencies be considered?
Recurrent sinopulmonary infections
Enteroviral infections (XLA)
Giardiasis
Autoimmune phenomenon
In selective IgA deficiency, what are CD19/20, IgG, IgA, IgM levels and postimmunization levels?
CD 19/20 Normal
IgG Normal
IgA
In XLA, what are CD19/20, IgG, IgA, IgM levels and postimmunization levels?
CD 19/20 Very low/absent
IgG
In CVID, what are CD19/20, IgG, IgA, IgM levels and postimmunization levels?
CD 19/20 Normal or low
IgG
In Hyper IgM, what are CD19/20, IgG, IgA, IgM levels and postimmunization levels?
CD 19/20 Normal
IgG
What are the infections associated with transient hypogammaglobinemia of infancy (THI)?
Sinopulmonary GI, thrush, meningitis (usually not severe) May be asymptomatic
What are the lab findings in transient hypogammaglobinemia of infancy?
IgG
What is the therapy of transient hypogammaglobinemia of infancy?
Mostly no Rx, may need prophylactic antibiotics, but rarely IVIG Usually resolved by 2–4 years old
What is the most common primary immunodeficiency disorder?
Selective IgA deficiency
What is the inheritance of selective IgA deficiency?
Unknown Some sIgAD + CVID has TACI mutation Most common primary immunodeficie ncy disorder
What are the infections in selective IgA deficiency?
Majority asymptomatic; Sinopulmonary , GI infections;
Autoimmune and atopic disease;
Rare: anti-IgA Ab -> transfusion reactions
What are the lab findings in selective IgA deficiency?
IgA
What are causes of secondary IgA deficiency?
Antiepileptics Sulphasalazin ecaptopril, thyroxin
What conditions might IgA deficiency be a part of?
Ataxia telangectasia
IgG2 subclass deficiency
chronic mucocutaneous candidiasis
What is the treatment for selective IgA deficiency?
Treatment and prophylactic antibiotics; and IVIG if concomitant specific antibody defect Monitor progression to CVID
What are the infections and clinical findings in specific antibody deficiency?
Sinopulmonary infections Allergic rhinitis
What are the lab findings in specific antibody deficiency?
Normal IgG, A, M Poor polysaccharide response despite pneumovax
What age does specific antibody deficiency occur in?
> age 2
What is the treatment for specific antibody deficiency?
Prophylactic ABx and IVIG Monitor progression to CVID
What is the mutation of X linked aggamaglobinemia?
BTK (Bruton’s tyrosine kinase)
What are the infections in XLA?
Sinopulmonary infections, atypical bacteria, GI infections, enteroviral encephalitis, septic arthritis, lymphoreticular and colorectal malignancies, bronchiectasis
Small/absent lymphoid tissue, no germinal cente
What are the lab findings in XLA?
Low IgG, A, M (
What stage does the maturation of B cells arrest at in XLA?
Maturational arrest at the pre-B lymphocyte stage
What types of test should you avoid to test for infectious disease in XLA?
Do not use serologic assays to diagnose infectious diseases—ex. ELISA for HIV Use PCR assays or cultures instead
What is the treatment for XLA?
IVIG treatment and ABx Rx
What is contraindicated in XLA?
Live immunizations contraindicated
What is the inheritance/mutation in autosomal recessive agamma-globulinemia?
Surrogate light chain (V pre-B; λ5), μ IgM heavy chain (Cμ), Igα, Igβ, BLNK
What are the infections/clinical findings in autosomal recessive agammaglobulinemia?
Same as XLA
Can be more severe and earlier onset than XLA
(XLA - Sinopulmonary infections, atypical bacteria, GI infections, enteroviral encephalitis, septic arthritis, lymphoreticula r and colorectal malignancies, bronchiectasis Small/absent lymphoid tissue, no germinal center)
What are the lab findings in autosomal recessive agammaglobulinemia?
IgG, A, M (
What is the most common mutation in autosomal recessive agammaglobulinemia?
μ IgM heavy chain—most common of AR agammaglobulinemia
What is the treatment for autosomal recessive agammaglobulinemia?
Same as XLA, which is:
IVIG treatment and ABx Rx Live immunizations contraindicated
What are the mutations in CVID?
Mostly unknown; ICOS, TACI; BAFF-R, CD19 complex, CD20
What are the infections/clinical findings in CVID?
Age >2 years old, sinopulmonary, GI infections, meningitis
Bronchiectasis, BOOP, autoimmune disease, GI/liver disease, granulomatous disease, nonHodgkin’s lymphoma, and gastric carcinoma
What are the lab findings in CVID?
IgG (
What is Good’s syndrome?
CVID + thymoma
What is associated with the noninfectious complications of CVID?
Reduced # of switched memory B cells shown to be associated with certain noninfectious complications (hematologic autoimmunity)
What is the treatment for CVID?
IVIG treatment and ABx Rx
No live vaccine
Pulmonary hygiene for bronchiectasis
Excise thymoma if present
What are the infections/clinical findings in IgG subclass deficiency?
mostly asymptomatic
What are the lab findings in IgG subclass deficiency?
Normal IgG and low level of ≥1 subclasses
IgG2 deficiency can occur with SIgAD with impaired Ab response to polysaccharide
Is IgG sublcass deficiency a true primary immunodeficiency?
Controversial if true PIDD—20% of population have subnormal of ≥1 subclasses (esp. IgG4)
What is the treatment for IgG subclass deficiency?
Rx as SAD in case of poor polysaccharide response
What is the inheritance/mutation in hyper IgM 2?
AR
AID deficiency
What is the inheritance/mutation in hyper IgM 4?
AR
UNG deficiency
What are the infections and clinical findings in hyper IgM2 and hyper IgM4?
Sinopulmonary and GI infections;
Lymphoid hyperplasia and adenopathy
CVID-like, but have increased autoimmune disease
What are the lab findings in Hyper IgM 2 and hyper IgM 4?
↓IgG, IgA, IgE, and normal or ↑ IgM;
Normal T-cell function
↑LN and giant germinal centers.
What are the AID and UNG genes required for?
AID (activation-induced cytidine deaminase) and UNG (uracil-DNA glycosylane) are required for class switch recombination and somatic hypermutation of B cell
Why are Hyper IgM2 and 4 less severe than Hyper IgM1, 3, and NEMO?
No T-cell defect -> less severe than HIGM1, 3 and NEMO defec
What is the therapy for hyper IgM 2 and 4?
IVIG
ABx Rx
No live vaccines
What stage of B-cell development is affected by BTK mutation?
Arrest in pre-B–cell stage
What are the differences between HIGM1/3 and HIGM2/4?
HIGM1/3 are combined immune deficiencies with more severe/wide spectrum of infections with absent LN and germinal centers due to defects in CD40L-CD40 interactions. HIGM2/4 are antibody deficiencies with less severe infections. Lymphoid hyperplasia and adenopathy are noted. Defects are in Bcell class switching and somatic hypermutation
