Diagnosis of Autoimmune Diseases

Question 1

What are the general principles of diagnostic testing?

Answer 1

• Diagnostic tests should be used to answer specific questions and/or to support a clinical diagnosis, but not as screening tools
• The ability of the tests to correctly discriminate between health and disease is improved when they are used in the appropriate population

Question 2

What is sensitivity?

Answer 2

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

Question 3

What is specificity?

Answer 3

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

Question 4

What is positive predictive value?

Answer 4

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

Question 5

What is negative predictive value?

Answer 5

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

Question 6

What are the different type of autoimmune diagnostic tests?

Answer 6

• Non specific
  
  • Inflammatory markers
• Disease specific
  
  • Autoantibody testing
  • HLA typing

Question 7

Which tests measure the non-specific markers of autoimmunity?

Answer 7

ESR - erythrocyte sedimentation rate (blood more viscous during inflammation)
CRP - C-reactive protein (more temporally sensitive)
Ferritin - increases during acute inflammation
Fibrinogen - increases
Haptoglobin
Albumin - decreases
Complement - increases

Question 8

What is rheumatoid factor?

Answer 8

Antibody (IgM, IgG or IgA) directed against the Fc portion of IgG

Question 9

What are the features of rheumatoid factor?

Answer 9

• Commonly found in rheumatoid arthritis but not diagnostic of the diseases (sensitivity and specificity around 70%)
• Can be seen with other diseases in which polyclonal stimulation of B cells is seen (chronic infections)
• High titers may be pathogenic in vasculitis

Question 10

What are the features of Anti-CCP (ACPA)?

Answer 10

ACPA more specific (95%) for RA then RF
Similar sensitivity to RF
Useful prognostic marker
ACPA positive patients tend to have more severe and erosive disease

Question 11

What is the clinical utility of measuring ANCA?

Answer 11

Particularly associated with Weneger’s granulomatosis

Does not indicate a need for continued treatment

Reemergence of ANCA in a patient who was ANCA -ve whilst in remission suggests a risk of disease flare.

Histopathology remains the gold standard for diagnosis in most cases

Negative ANCA assays do not exclude AASV since 10%-50% of patients may be ANCA neg

Persistence of ANCA in the absence of clinical indications of active disease.

Question 12

What is the role of testing for autoantibodies in T1DM?

Answer 12

Disease comfirmation

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

Question 13

Name an autoimmune liver disease thought to be associated with anti-mitochondrial antibodies.

Answer 13

Primary biliary sclerosis

Question 14

Name an autoimmune granulomatous vasculitis in which ANCA are detected.

Answer 14

Wegener’s granlulomatosis

Question 15

Acronym for a very specific antibody in rheumatoid arthritis?

Answer 15

ACPA

Question 16

What is the relevance of rheumatoid factor?

Answer 16

Commonly found in rheumatoid arthritis but not diagnostic of the diseases (sensitivity and specificity around 70%)

Can be seen with other diseases in which polyclonal stimulation of B cells is seen (chronic infections)

High titers may be pathogenic in vasculitis

Question 17

What is the relevance of anti-neutrophilic cytoplasmic antibodies (ANCA)?

Answer 17

Antibody specific for Weneger’s granulomatosis.

Question 18

In which liver disease would you detect Anti-mitochondrial Ab?

Answer 18

Primary biliary sclerosis

Question 19

What antibodies are found in autoimmune hepatitis?

Answer 19

Anti-smooth muscle and anti-liver/kidney/microsomal (LKS) Abs

Question 20

How are these antibodies detected?

Answer 20

Detected by immunofluorescence screening using rodent tissue block (oesophagus, liver and kidney) and antigen specific ELISA.

Question 21

What autoAbs are detected in T1DM and what happens to their titres as the disease progresses?

Answer 21

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

Titres diminish to nothing as there is complete destruction of Beta cells in Islets of Langerhans