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2. CP - Core Immunology > (9) Autoimmunity Diagnosis > Flashcards

(9) Autoimmunity Diagnosis Flashcards

1
Q

Should diagnostic tests be used as screening tools?

A

No

They should be used to answer specific questions and/or to support a clinical diagnosis but not as screening tools

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2
Q

When is the ability of a diagnostic test to correctly discriminate between health and disease improved?

A

When they are used in the appropriate population

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3
Q

What is ‘sensitivity’?

A

Measure of how good the test is in identifying people with the disease

a/(a+c)

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4
Q

What is ‘specificity’?

A

Measure of how good the test is at correctly defining people without the disease

d/(b+d)

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5
Q

What is ‘positive predictive value’?

A

The proportion of people with a positive test who have the target disorder

a/(a+b)

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6
Q

What is the ‘negative predictive value’?

A

The proportion of people with a negative test who do not have the target disorder

d/(c+d)

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7
Q

What graph can be used to give you an idea as to whether a diagnostic test would be valuable?

A

A normogram

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8
Q

What is the likelihood ratio (LR)? (used in a normogram)

A

probability of finding in patients with the disease / probability of same finding in patients without disease

The higher the LR, the more useful the test

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9
Q

What are the 3 parts of a normogram that should be connected by a line?

A
  • pre-test probability
  • likelihood ratio
  • post-test probability
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10
Q

Give a type of non-specific diagnostic test

A

Inflammatory markers

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11
Q

Give 2 types of disease-specific diagnostic test

A
  • autoantibody testing

- HLA typing

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12
Q

Give examples of non-specific markers of systemic inflammation

A
  • ESR
  • CRP
  • ferritin
  • haptoglobin
  • albumin
  • complement

(acute phase response proteins)

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13
Q

What are acute phase response proteins?

A

Class of proteins whose plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation

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14
Q

How is C-reactive protein (CRP) an inflammatory marker?

A

Produced by liver after infection/inflammation

Changes acutely and so useful to measure treatment within 24 hours

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15
Q

What is ESR and how is it an inflammatory marker?

A

Erythrocyte sedimentation rate

Measures viscosity of plasma - viscosity increases after an inflammatory response

ESR takes a while to fully resolve after the infection + treatment

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16
Q

Does albumin (an inflammatory marker) increase or decrease in acute inflammation?

A

Goes down

Synthetic capacity of liver reduces

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17
Q

What are origins of ANA (antinuclear antibodies)?

A

LE phenomena in 1948

dsDNA identified in 1957

Anti-SM in 1966

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18
Q

What was noticed when bone marrow was taken and looked at from an SLE patient?

A

The nuclei of the erythrocytes had been engulfed by neutrophils and macrophages

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19
Q

What was noticed when the serum of an SLE patient was analysed?

A

Antibodies against double-stranded DNA (dsDNA) were present - autoantibodies directed to the nucleus

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20
Q

What are some possible specific targets of autoantibodies?

A
  • double stranded DNA (dsDNA)
  • RNP (ribonuclear proteins, protein machinery that deals with dsDNA transcription and translation)
  • Ro (RNP)
  • La (RNP)
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21
Q

What does ENA stand for?

A

Extractable nuclear antigens

These include the things that autoantibodies might be specifically targeted to

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22
Q

When might you ask for an ANA detection test?

A

Patient with hair loss, mouth ulcers, joint pain etc. Diagnostic test to confirm suspicions of lupus

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23
Q

What does an ANA detection test do?

A

It looks for autoantibodies against the nucleus in the serum

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24
Q

Why are secondary antibodies used in an ANA detection test?

A

They are used for visualisation - fluorescently tagged

They recognise the constant fc region of the ig molecule

Can see it brightly where there are autoantibodies against the nucleus

25
Q

What techniques are used to detect anti-dsDNA antibodies?

A
  • crithida lucillae assay
  • farr essay
  • ELISA
26
Q

What techniques are used to detect ENAs?

A
  • immunoblots
  • individual ELISAs
  • combination of antigens
27
Q

How many antibodies described in SLE?

A

> 100

28
Q

What is a newer more modern method of ANA detection?

A

Multiplex assessment of non-organ-specific autoantibodies with a novel microbead-based immunoassay

Can detect up to 20 things in a single serum sample

29
Q

What is the sensitivity and specificity of an ANA test for SLE?

A

sensitivity = >95%

specificity = 60%

30
Q

What is the sensitivity and specificity of a dsDNA test for SLE?

A

sensitivity = 70%

specificity = 95%

31
Q

What is rheumatoid factor (RF)?

A

RF is the autoantibody first found rheumatoid arthritis

It is an IgM, IgG or IgA directed against the Fc portion of IgG

32
Q

Is RF diagnostic of rheumatoid arthritis?

A

Commonly found in rheumatoid arthritis but not diagnostic, sensitivity and specificity around 70%

33
Q

What other diseases other than rheumatoid arthritis can rheumatoid factor be seen in?

A

Other diseases in which polyclonal stimulation of B cells is seen (chronic infections)

34
Q

What is vasculitis and what can cause it?

A

Inflammation of the blood vessels

May be caused by immune complexes precipitating in the capillaries

35
Q

What is a more specific biomarker for rheumatoid arthritis than rheumatoid factor?

A

Anti-CCP (ACPA)

Present in 95% of patients with rheumatoid arthritis

36
Q

What are ACPAs?

A

Anti-citrullinated protein antibodies

They are auto-antibodies that are directed against peptides and proteins that are citrullinated. They are present in the majority of patients with rheumatoid arthritis

37
Q

How does the sensitivity of ACPAs compare to RF?

A

Similar sensitivity

38
Q

How are ACPAs useful?

A

They are a useful prognostic marker

Allows us to pick up RA much earlier in progression of disease

Can find patients even in pre-clinical stage

39
Q

ACPA positive patients tend to have what?

A

More severe and erosive disease

And so more aggressive therapy can be used

40
Q

What are ANCAs?

A

Anti-neutrophilic cytoplasmic antibodies

They are a group of autoantibodies, mainly of the IgG type, against antigens in the cytoplasm of neutrophil granulocytes and monocytes. They are detected as a blood test in a number of autoimmune disorders, but are particularly associated with systemic vasculitis

41
Q

When were anti-neutrophilic cytoplasmic antibodies (ANCA) first described?

A

In 1982 as an incidental finding when using granulocytes as a substrate for ANA (GS-ANA)

42
Q

In 1985, ANCAs were first described as an antibody specific for what?

A

Wegeners granulomatosis

43
Q

As well as neutrophils, what can be used as a substrate for ANA?

A

Fibroblasts

used in SLE

44
Q

What are the two types of ANCA?

A
  • cytoplasmic (c)ANCA

- perinuclear (p)ANCA

45
Q

What are cytoplasmic (c)ANCAs?

A

Antibodies directed to cytoplasm, sparing the nuclei

See granular fluorescence of neutrophil cytoplasm with nuclear sparing

46
Q

What are perinuclear (p)ANCAs?

A

Antibodies directed to the nuclei, spring the cytoplasm

See apparent fluorescence of the nucleus only

47
Q

How are neutrophils treated when being used as substrates for ANCAs?

A

Treated in a specific way using ethanol, allows the nucleus to be better visualised

48
Q

What are the target antigens for cytoplasmic (c)ANCAs?

A
  • PR3 (90%)
  • azurocidin
  • lysozyme (1%)
  • MPO
49
Q

What are the target antigens for perinuclear (p)ANCAs?

A
  • MPO (70%)
  • azurocidin
  • B-glucuronidase
  • cathepsin G (5%)
  • PR3
50
Q

Positive ANCA is extremely useful in suggesting the diagnosis in the proper clinical setting but what remains the gold standard for diagnosis in most cases?

A

Histopathology

51
Q

Do negative ANCA assays exclude AASV?

A

No

10-50% of patients may be ANCA negative

52
Q

Does persistence of ANCA in the absence of clinical indications of active disease indicate a need for continued treatment?

A

No

53
Q

What does a reemergence of ANCA positive in a patient who was ANCA negative whilst in remission suggest?

A

A risk of disease flare

The temporal correlation between the return of ANCA and a disease flare is poor

54
Q

Which autoantibody is specific for primary biliary sclerosis?

A

Anti-mitochondrial Ab

55
Q

Which autoantibodies are found in autoimmune hepatitis?

A

Anti-smooth muscle

Anti-liver/kidney/microsomal (LKS)

56
Q

What are the several types of autoantibodies in type 1 DM?

A
  • islet cell antibodies
  • anti-GAD65 anti-GAD67
  • anti-insulinoma antigen 2 (IA-2)
  • insulin autoantibodies (IAAs)
57
Q

Autoantibodies in type 1 DM disappear with what?

A

With progression of disease and total destruction of B islet cells

58
Q

What is the role of autoantibodies in diagnosis of type 1 DM?

A
  • disease conformation
  • to identify relatives and patients at risk of developing autoimmune diabetes
  • negative predictive value of ICA and IAA is almost 99%
  • increased risk of disease development with greater number of different autoantibodies present and younger age of patient
59
Q

What is involved in the future of diagnostic testing in investigation of autoimmune diseases?

A
  • cytokine determination in serum
  • detection of antigen specific autoimmune T and B cells
  • T-reg detection, measure of therapeutic response
  • personalised medicine, genetic profiling to determine individual risk of the disease and to tailor the most appropriate therapy

2. CP - Core Immunology (7 decks)

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