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Labs Medicine > Immunology Testing > Flashcards

Immunology Testing Flashcards

1
Q

What are the four ways an ANA can be helpful?

A
  1. help diagnose a patient who is suggestive of an AI disease
  2. hep exclude AI disease
  3. subclassify patients with AI
  4. monitor disease activity
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2
Q

What is the sensitivity of a positive ANA for SLE?

A

95% - pretty good

less so for other autoimmune diseases - not specific at all

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3
Q

What are some non-AI causes of a +ANA?

A

Mono, hepC, lymphoproliferative disease, HIV, anti-synthetase syndrome (cytoplasmic staining)

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4
Q

How is an ANA run?

A

A HEp2 (human epithleial cell tumor line) is used with acetone fixed substrate (more sensitivie)

you get a report pattern and titer (1:80 is considered significant). But be cautious: up to 20% of people will have a normal titer over 1:80 and some may even have a normal titer over 1:320. So take in clinical context.

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5
Q

What pattern of +ANA testing is usually seen in SLE?

A

homogeneous pattern

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6
Q

Describe this homogeneous pattern.

A

You get positive staining of the cells while cytoplasm is negative - this is because the stain divides the cell chromatin.

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7
Q

What are the two antibodies that give rise to this homogeneous pattern?

A

Anti-DNA histone complex

Anti-dsDNA

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8
Q

What are the two strategies used to identify this Anti-dsDNA?

A

C. lucilliae

ELISA (mostly taking over - more sensitive, but not as specific)

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9
Q

Antibodies to extractible nuclear antibens will result in what +ANA pattern?

A

speckled

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10
Q

What are some examples of these “extractible nuclear antigens”?

A

Sm, RNP, Ro/SSa, La/SSb, Scl-70, centromere, PCNA

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11
Q

Anti-smith is very specific for SLE patients, but only ___% of SLE patients will have it.

A

25

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12
Q

Anti-U1nRNP is suggestive of what diagnosis?

A

mixed connective tissue disease

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13
Q

What symptoms are associated with antibodies to RO/SSA in SLE?

A 
photosensitivity
sicca
thrombocytopenia
subacute cutaneous LE rash
Neonatal lupus (maternal IgG crosses placenta - can lead to complete heart block and pregnancy loss!)
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14
Q

The Nucleolar pattern of +ANA has various specificities and an also be present in in 20% of people with what disease?

A

scleroderma

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15
Q

The centromere +ANA pattern is from antibodies against what?

A

proteins present on active centromeres during meiosis and mitosis: CENP-A, CENP-B, CENP-C

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16
Q

What disease is the centromere +ANA pattern associated with?

A

a CREST variant with calcinosis and telangiectasis but less renal invovlement

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17
Q

What are the two strategies for identification of the specific antibodies involved in a +ANA?

A

ELISA or multiplex

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18
Q

Describe multiplex testing

A

uses colored polystyrene beads coated with single purified antignes

uses fluorescein-labeled antihuman IgG that is read in a dual-laser flow cytometer

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19
Q

What is the primary use for ANCA testing?

A

evlauate patients with suspected vasculitis (usually either granulomatosus with polyangiitis or microscopic polyangiitis)

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20
Q

cANCA is usually due to anti-_____

A

anti proteinase 3

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21
Q

pANCA is usually due to anti-____

A

myeloperoxidase

22
Q

Granulomatosus with polyangiitis is usually associated with which one?

A

cANCA

23
Q

So microscopic polyangiitis is associated with…

A

pANCA

24
Q

What are the criteria for diagnosis of RA?

A 
Need 5 of the following:
morning stiffness
pain on motion
joint swelling
symmetrical joint involvement
subQ nodules
x-ray changes
histologic changes on biopsy
\+RF
\+Anti-CCP
25
Q

What is rheumatoid factor?

A

Usually IgM antibody that reacts with the Fc portion of IgG (all, not just human)

26
Q

Describe the rheumatoid factor test.

A

Usually done with ELISA (often with rabbit IgG)

can also do it with latex particles coated with non-human or human IgG, which will agglutinate the RF is present; quantitation done by titering the antibody.

27
Q

WHat are some other conditions with RF present?

A 
bacterial endocarditis
syphilis
hep B and C
infectious mono
myeloma
cryoglobulinemias
sarcoidosis
28
Q

What is cyclic citrullinated peptide derived from?

A

fillagrin, which is associated with keratin filaments

29
Q

True or false: +anti-CCP is predictive of milder disease.

A

false - predictive of more severe disease

30
Q

WHat is the positive predictive value of CCP and RF together?

A

over 97% - huge

31
Q

What are the main cytokines released in RA?

A

IL-6, IL-12, TNF-a, IL-15

32
Q

What are some clinical manifestations of celiac disease?

A

chronic diarrhea, weight loss, malabsorption, abdominal distension (typical)
dermatitis herptiformis
osteoporosis (atypical)
short status (atypical)
neuropsychiatric (dep, anx, ataxia, migraines, neuropathy, etc.)

33
Q

What is the incidence for celiacs?

A

1:100 (wow)

34
Q

What do you see on GI biopsy in celiacs?

A

villous atrophy

35
Q

Describe the pathophysiology of celiac disease.

A

gluten-reactive CD4+ T cells in the lamina propria of the upper GI tract react with the alpha-gliaden peptide sequence in gluten

presents peptides by HLA-DQ2 or 8, which triggers production of proinflammatory cytokines

tissue transglutaminase deaminates the peptides, and the deaminated glutamine peptides then bind more avidly to HLA sites, further increasing immunogenicity

enterocytes produce IL-15 which activates NK cells

all leading to villous atrophy, crypt hyperplasia and intraepithelial lymphocytosis

36
Q

We use IgA anti-endomysial antibodies as a highly specific test for CD. What does it bind?

A

tissue transglutaminase

37
Q

Why is tissue transglutaminase a good antigen to test for in CD?

A

it’s released from intestinal mucosa with injury and also plays a role in the pathogenesis of disease (deaminates glutamine to glutamic acid, which binds more avidly to HLA-DQ2 and 8 as before)

38
Q

Which immunodeficiency is much more common in CD than in the general population?

A

IgA deficiency

39
Q

What test is the most efficient for making a diagnosis of CD?

A

IgA anti-tissue transglutaminase

40
Q

What test should you run to make the diagnosis of CD in IgA deficient patients? (that is if they’re otherwise low risk - lots of false positives in moderate to high risk patients)

A

IgG anti-deaminated gliadin

41
Q

What are the two common HLA haplotypes in CD?

A

Hinting at them before: HLA-DQ 2 (95%) and 8 (5%)

absence has high negative predictive value and virtually excludes CD

42
Q

What is the best antibody to monitor treatment in CD?

A

anti-tTG

normal levels will be reached after 3 to 12 months of gluten free diet

43
Q

What antibodies are associated with Type I Autoimmune hepatitis?

A 
ANA
anti-SM
anti- soluble liver antigens
anti-saccharomyces cerevisiae
anti asialoglycoprotein receptor
pANCA
44
Q

What antibodies are associated with Type 2 autoimmune hepatitis?

A

anti liver/kidney microsomes (cyt p450)

anti liver cytosol antigen

45
Q

Type 1 autoimmune hepatitis is associated with what HLA haplotype?

A

DR3

46
Q

Type 2 autoimmune hepatitis is associated with what HLA haplotypes?

A

DRB1

DQB1

47
Q

Anti-smooth muscle antibodies come in different flavors specific to specific parts of myocytes. WHat’s the most common one in autoimmune hepatitis?

A

anti-actin antibodies (this is more sensitive and specific than the general anti-smooth muscle antibodies)

48
Q

pANCA is associated with type 1 autoimmune hepatitis, but instead of being directed against myeloperoxidase as it is in the vasculitides, what is the target?

A

myeloid 50kD nuclear envelope protein

note: this atypical pANCA is also found in ulcerative colitis

49
Q

How does primary biliary cirrhosis present?

A

usually women ages 30-65 with fatigue, pruritus, hyperpigementation/jaundice, arthropathy common,

sjogrens in 50%

increased alk phos, slight increase in aminotransferases, HLD

50
Q

What antibody is associated with PBC?

A

anti-mitochondrial antibodies

also ANA in 30%

51
Q

What are the four autoantigens that anti-mitochondrial antibodies go after?

A

E2 subunit of PD

2-oxo-acid dehydrogenase

ketoglutaric acid dehydrogenase

hydrolipoamide dehydrogenase

(all involved in oxidative phosphorylation within the mitochondria)

Labs Medicine (27 decks)

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