What immune disease is charactertized by:
Presents approximately 2-6 months of age (after maternal antibody wanes)
Extremely low or absent immunoglobulin levels (IgG <200 mg/dl)
Recurrent upper respiratory infections, Giardia infestations
The correct term now is Bruton's Thymidine Kinase (BTK) Deficiency
CD19 positive B cells are absent in peripheral blood. Most common defect is in a B cell progenitor kinase, located on the long arm
of chromosome X (Xq22)
Treated with intravenous Immunoglobulin
An autosomal recessive form of this syndrome exists and is related to defects in the genes encoding the u heavy chain gene, CD79A and CD179B
How do you differentiate Bruton's agammaglobulinemia from transient hypoalbuminemia of infancy?
Trans Hypoalb will present approximately 5-6 months
IgG and IgA low, IgM may be normal to low
Recurrent upper respiratory infections
CD19 positive B cells ARE present
Hypogammaglobulinemia may last up to 2 years.
Cause is undefined
What immune disease may be a B or T cell defect and can cause a Th1 imbalance with elevated IL12 and gamma interferon and it is autosomal recessive and from ICOS defect?
*These patients get recurrent upper and lower respiratory infections, intestinal bacterial overgrowth and Giardia intestinalis infection
B cells can't differentiate into plasma cells
Germinal centers are HYPERplastic
What immune disease presents in the first year of life, IgM levels are normal to elevated (100-1000 mg/dl), IgG, IgA and IgE levels are low, CD4 cell increase may occur and it is due to a defect is in the gene (Xq26 ) coding for the T cell protein, CD154 (CD40 Ligand) molecule?
CD40 Ligand Deficiency (used to be called Hyper IgM Deficiency)
CD154 binds to CD40 initiating class switching
in B cells. This defect prevents T cells from inducing B
cells to undergo a class switch. Thus the B cells
produce IgM, without switching to another isotype.
Autosomal recessive form does exist, involving the TNFRSF5 gene
What is the mutation in DiGeorge syndrome?
Chromosome 22q11.2 missing in DiGeorge,
What immune disease is characterized by IL-2 receptor gamma chain mutation, (Xq13); also affects receptors for IL-4, 7, 9, 15 and 21. Phenotype is T- B+ NK+or-?
What immune disease is characterized by not having ANY T, B or NK cells (ie what the boy in the bubble had)?
Adenosine deaminase deficency
What genes are involved in 1) MHC Class I deficiency and 2) MCH Class II deficiency?
Autosomal recessive disorder
– Class 1 deficiency- TAP1, TAP2 genes
– Class II deficiency- RFXAP, RFXANK genes
What immune disease is characterized by:
Defect in CD18 gene (INTGB2 gene, 21q22.23), preventing proper LFA-1 adhesion molecule formation. This molecule is important in allowing neutrophils to migrate out of blood vessels into the tissues. It is autosomal recessive disease and causes recurrent soft tissue infections; impaired
Leukocyte Adhesion Deficiency, Type I
This cell is a neutrophil engulfed Ab coated cell
nucleus. What disease can this be seen in (not real life but on boards)?
What ANA pattern is seen here and what antigens are present?
Antigens: DNA, histone, dsDNA, ssDNA
Associations: SLE, drug-induced lupus, RA
What ANA pattern is this and what antigen is it associated with?
Anti dsDNA quantitation with Crithidia luciliae
The kinetoplast staining is positive dsDNA and will appear as two (sometimes three) dots. The only staining that is important is the KINETOPLAST
The other two dots that are staining regardless are the basal body and the nucleus but the nucleus is usually poorly visualized even if sera is ANA positive.
What serum markers help differentiate lupus from mixed connective tissue disease?
MCTD will be positive with anti-RNP but NOT anti-smith
Lupus will be positive for both
What ANA pattern is this and what antigen is it associated with?
Antigen: SSA (Ro), SSB (La), Smith, U1-RNP, PCNA, Scl-70 (fine speckling)
Associations: SLE, MCTD, Sjogren, Scleroderma
What immunologic findings do scleroderma patients display in regards to levels of CD4, CD8 and B cells?
Normal CD8 suppressor activity
Increased CD4 TH activity
Increased B cell activation
What ANA pattern is seen here and what antigen is this associated with?
Antigens: RNA polymerase I, U3-RNP (fibrillarin), PM-Scl
*NOTE* if you see the nucleolar pattern with prominent green background staining, that is most likely specific to fibrillarin (U3-RNP)
Associations: Scleroderma, Polymyositis/Scleroderma overlap
What ANA pattern is seen here and what antigen is it associated with?
Antigens: CENP-A, B and C
Associations: scleroderma (with CREST syndrome), Raynoud
*NOTE* the mitotic cells show a speckled pattern whereas in the normal speckled pattern, you won't see these mitotic figures
What vasculitis is immune complex mediated?
Polyarteritis nodosa (secondary to SLE, HepB)
What autoimmune vasculitis is antibody mediated?
Kawasacki disease (necrotizing vasculitis, primarily pediatric disease)
Name three diseases associated with pANCA.
IBD (60-70% with UC, 40% with Crohn's)
*Anti-Saccharomyces ceriviseae Ab (ASCA) is asssociated with Crohn's
Regarding c-ANCA and p-ANCA, what are these antibodies against?
cANCA is usually antibody to proteinase 3
pANCA is usually antibody to myeloperoxidase
*HINT* Remember that P ANCA does NOT go with P protein
What is atypical (X) ANCA and what is it associated with?
UC and primary sclerosing cholangitis
Possible antigen targets: lactogerrin, cathepsin G, histone H1, BPI (bacterial permeability increasing protein)
BQ! Explain the technical process for ANCA evaluation (actually pretty interesting process and according to OSLER guy, this shows up commonly on boards).
FIRST: Screen on ETOH fixed neutrophils
--Cytoplasmic speckling indicates cANCA
--Perinuclear or nuclear staining indicates either pANCA, ANA or
SECOND: Run specimen on formalin fixed neutrophils
*why? Because during ethanol fixation, the granules in neutrophils coalesce around the nucleus where in formalin fixed neutrophils they stay out in the cytoplasm so on a FF slide there is NO difference in a C or P ANCA that is why screening is done on ethanol slides because you can tell the difference
--Cytoplasmic staining on FF fixed neutrophils suggest pANCA
– MPO remains in the cytoplasm during formalin fixation
--Negative result suggests ANA or xANCA
– Anti DNA may remain positive on FF neutrophils
THIRD: Run on Hep-2 to rule out ANA
Shown are ethanol fixed neutrophils. What is this diagnostic of?
*in ethanol fixed neutrophils, c-ANCA is cytoplasmic whereas perinuclear staining could be either p-ANCA, ANA, or atypical ANCA because the granules coalesce around the nucleus so if you get cytoplasmic staining on ethanol fixed, you have c-ANCA but if you have perinuclear staining, you have to then test formalin fixed neutrophils where BOTH c-ANCA and p-ANCA will stain the cytoplasm but will be negative if ANA or atypical ANCA is the culprit. So then follow it with Hep2 cells to check for ANA and if that is neg, you have atypical ANCA by exclusion.
Therefore cytoplasmic staining in ethanol fixed is c-ANCA. Perinuclear staining on ethanol fixed followed by cytoplasmic staining in formalin is p-ANCA. Perinuclear staining on ethanol followed by negative formalin followed by positive ANA Hep2 is ANA and if Hep2 is negative its atypical ANCA
This is a mouse kidney. What antibody is this?
85% of PBC
Reactive with the cytoplasm of parietal cells of the staomch and renal tubular cells in the mouse stomach/kidney substrate
*note AMA also seen in 10-15% of autoimmune hepatitis
What antibodies are seen in autoimmune hepatitis (there are two types)?
Type 1- Anti-Smooth muscle Ab, ANA
Type 2- Anti-Liver Kidney Microsomes (Cytochrome P450 D26)
What immunodeficiency is more common in patients with Celiac disease?
IgA deficiency occurs more frequently in celiac
disease than in the general population.
– 1/700 in normal population
– App 4% in celiac disease patients
This is monkey esophagus. What is the antibody?
Anti-endomysial antibody (Celiac)
What is the single best test for celiac disease?
IgA anti TTG is the best single test for Celiac Disease
IgA Anti TTG and Anti Deamidated Gliadin appear to be the most useful combination of serological assays
– If the above tests are negative, and the patient is IgA deficient, or if clinical suspicion of Celiac is still high, then an IgG anti TTG and IgG anti d-Gliadin is in order
HLA Typing- DQ2 and DQ8
What chromosomes are the following found:
1) kappa light chain genes
2) lambda light chain genes
3) heavy chain genes
4) HLA proteins
1) Chr 2
2) Chr 22
3) Chr 14
4) Chr 6p