Term
| Among cellular, phagocytic, complement and antibody deficiencies, which is the most common? |
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Definition
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Term
| Clinical presentation of antibody deficiency |
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Definition
1. increased susceptibility to infection
2. recurrent URIs, LRTIs
3. GI infections
4. Autoimmunity, cancer |
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Term
| Which organisms cause infections in antibody deficiency? |
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Definition
Encapsulated orgs: H Flu, S pneumoniae
Gram neg rods (esp in pts rx'd with broad-spectrum abx)
Mycoplasma, ureaplasma (unique susceptibility; remember to cover for these)
Viruses, esp enteroviruses
Protozoa (giardia, crypto |
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Term
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Definition
decrease in all Ig isotypes (IgG <200)
very reduced B cells (<1%)
Btk mutation |
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Term
| Auto recessive agammaglobulinemia: defect and mutation |
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Definition
decrease in all Ig isotypes
reduced b cells
mutations in mu (no surface expression of IgM), lambda5 (for signal transduction of pre-BCR), Ig-alpha (for BCR signaling), BLNK (downstream signalling of BCR) |
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Term
| Selective IgA deficiency: defect and mutation |
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Definition
decreased IgA (<10)
rarely assoc with IgG2 deficiency and/or CVID
TACI mutations in some pts |
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Term
| IgG2 deficiency: mutation |
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Definition
| small subset have mutation in IgH gamma2 locus |
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Term
| CVID: defect and mutation |
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Definition
hypogammaglobulinemia
normal or decreased b cells
mutations in ICOS and TACI in some pts |
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Term
| ICF syndrome: defect and mutation |
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Definition
hypogammaglobulinemia
occas mild t cell defects
mutations in DNMT3B |
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Term
| X-linked HyperIgM: defect and mutation |
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Definition
defects in T helper-cell mediated activation of B cells, macrophages and dendritic cells; defects in somatic mustation, class switching and germinal center formation; defective cell-mediated immunity
mutation in CD40L |
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Term
| Auto recessive HyperIgM with cell-mediated immune defects |
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Definition
defects: same as X-linked HyperIgM
Mutations in CD40 and NEMO |
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Term
| Auto recessive with antibody defect only: defect and mutation |
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Definition
defects in somatic mutation and isotype switching
mutations in AID, UNG (needed for Ig switch recombination and Ig somatic hypermutation) |
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Term
How to screen for Btk mutation?
Is Btk mutation mostly inherited or spontaneous?
What is the significance of null mutations (no protein made)? |
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Definition
FACS for Btk protein
80-85% are familial
Null mutations are associated with more severe clinical phenotype. |
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Term
| Name a vaccine related complication in XLA |
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Definition
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Term
| IgA deficiency: clinical features and Rx |
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Definition
1:400 live births
most pts are normal; some have sinpulmonary infxns or GI (giardia) infections
increased rate of atopy and autoimmune disease |
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Term
| IgA deficiency: should you treat with IVIG? |
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Definition
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Term
| IgA deficiency and heterophile antibodiess |
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Definition
False negative: due to lack of IgA. Example: IgA-anti TTG in celiac disease
False positive: due to increased presence of heterophile antibodies; example: ELISA assays, eg pregnancy tests |
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Term
| What are heterophile antibodies? |
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Definition
| Antibodies that recognize an antigen different than the antigen that originally induced the antibody response (example: EBV) |
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Term
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Definition
high IgM (may be normal in AID/UNG mutations)
low IgG
low IgA |
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Term
| Clinical presentation of HyperIgM |
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Definition
recurrent sinopulm infxns
lymph node hyperplasia
autoimmunity |
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Term
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Definition
| like other forms of hypogam: IVIG |
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Term
1. What is the etiology of CVID?
2. Are most cases inherited? |
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Definition
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Term
| CVID: immunologic features of "probable" diagnosis |
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Definition
decrease in 2 of 3 major isotypes (>2 SD below mean):
low IgG and low IgA
or
low IgG and low IgM
Also: absent isohemaggutinins, poor vaccine response |
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Term
| CVID: immunologic features of possible diagnosis |
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Definition
low IgG
absent isohemagglutinins and poor vaccine response |
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Term
| Can you diagnose CVID when IgG level is normal? |
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Definition
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Term
| Immune features of CVID vs steroid-induced hypogam |
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Definition
CVID: IgG < 400 w/very low IgA or low IgM with very poor vaccine antibody response
Steroid-induced hypogam: IgG usally >400 with normal/slightly reduced IgA/IgM; vaccine antibody response is normal or slightly reduced |
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Term
| CVID: name 4 GI abnormalities |
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Definition
Atrophic gastritis
Malabsorption (B12, iron)
Inflammatory bowel disease
Focal nodular hyperplasia |
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Term
| Name the autoimmune problems in CVID |
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Definition
| Cytopenias: ITP, AHA, CD4 lymphopenia |
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Term
| Name the major causes of death in CVID |
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Definition
pulmonary disease
Cancer (B cell lymphomas > gastric)
Autoimmune complications
Liver disease
Infection |
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Term
| Name the types of lung disease in CVID |
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Definition
Restrictive: GLILD, BOOP, malignancy
Obstructive: bronchiectasis (#1), asthma, BO |
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Term
| Name the liver and spleen complications of CVID |
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Definition
Liver: nodular regenerative hyperplasia, autoimmune hepatitis, granulomas
Spleen: granulomas |
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Term
| How should you screen for interstitial lung disease in CVID? |
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Definition
High res chest CT
(CXR can be falsely normal) |
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Term
| What is the significance of low switched IgD-/CD27+ memory B cells in CVID? |
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Definition
| Lack of switch results in more severe phenotype (granulomas, lymphadenopathy, splenomegaly) |
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Term
TACI= transmembrane activator and calcium modulator
How is it relevant in CVID? |
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Definition
Expressed on B cells
Ligands: BAFF, APRIL
TACI mutations occur in some with CVID (higher rate of autoimmunity, splenomegaly, lymphadenopathy) |
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Term
ICOS and CD19
ICOS=inducible costimulator
Why are they relevant in CVID? |
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Definition
ICOS: expressed on activated T cells
CD19:expressed on all B cells
Mutations in ICOS and CD19 are rare and are assoc with less severe phenotype (no autoimmunity, lymphoprolif, etc) |
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Term
| Diagnostic studies in antibody deficiency: role of serologic studies |
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Definition
don't order serological assays
Serological assays measure antibodies in gammaglobulin in pts on IVIG
Diagnosiis of infectious disease must be done by culture, PCR or other direct method |
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Term
| Treeatment of CVID/HIM/Agammaglobulinemia |
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Definition
IVIG or subcut IgG: 400-600 mg/kg/mo
Avoid live vaccines
Aggressive Rx of infxns
Aggressive pulm hygiene for bronchiectasis
No evidence to support prophylactic abx |
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Term
| Specific antibody deficiency |
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Definition
Abnl response to vaccines, esp polysac antigens (Normal values are NOT established)
Normal IgG, IgA, IgM
Normal T cell fxn
Recurrent sinopulm infxns |
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Term
IgG subclass deficiency
What is IgG2 deficiency associated with? |
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Definition
Normal total IgG
reduction in 1 or more IgG subclasses
Controversy whether this is truly a PIDD as 20% of pop has subnormal levels
You should assess response to vaccines
IgG2 def is sometimes assoc with IgA def and these pts are more likely to have impaired response to polysac antigens |
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Term
Physiologic hypogam of infancy
IgG at birth
When does IgG nadir occur?
QUIGs at age 1 |
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Definition
Birth: serum IgG = maternal IgG
IgG nadir: 3-6 mos (400mg/dl)
At age 1, IgG and IgM are 60% of adult level. IgA is 20% of adult level |
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Term
| Transient hypogam of infancy: definition and manifestations |
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Definition
Def: prolongation of physiologic hypogam
IgG >2 SD below age matched controls, +/- decreased IgA, IgM
Persists beyond age 6 mos
Must exclude other causes
IgG normalizes by age 2-4 y
Some may have impaired vaccine response
Some have increased infxn; if so, Rx with prophylactic abx and IVIG |
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