T2-L3: Diagnosis of Autoimmune Diseases

Question 1

What is the likely clinical diagnosis of the following case:

• 51 yo lady
• 18month history of SOB on exertion
• Saw respiratory team and diagnosed with pulmonary fibrosis
• Fatigue, aches and pains
• Thickening of skin on hands and changes in the skin around her mouth
  Examination
• Sclerodactyly both hands
• Livedo reticularis on the legs
• Cool feet on palpation

Answer 1

Clinical diagnosis of scleroderma (diffuse systemic sclerosis) and started immunosuppression treatment.

Question 2

What are the types of diagnostic tests?

Answer 2

Non specific: 
- Inflammatory markers
Disease specific:
- Autoantibody testing
- HLA typing

Question 3

Give non-specific markers of systemic inflammation.

Answer 3

Non-specific - looking at the patients inflammatory marker. It tells you something is going on but not what.
		Examples include:
		- ESR
		- CRP
		- Ferritin
		- Fibrinogen
		- Haptoglobin
		- Albumin
		- Complement

Question 4

What is ANA? How does testing work?

Answer 4

ANA Antinuclear antibodies - Antibodies in the blood bind to cells in the nucleus. We can then be more specific and identify subtypes of antibody that bind to different parts of the cell nucleus.

	ANA testing: In the case of ANA Testing, Hep2 is the antigen. This is found on the well. This is incubated in the patients blood. A Florescence antibody is added to see if antibodies bind. It creates a pattern read through Florence. Patterns correlate with particular types of antibody and so particular types of disease.

Hep2 is a malignant cell line. It allows us to have visualisation of a cell nucleus to see how binding is.

Question 5

Other than ANA, how can we detect dsDNA and ENAS?

Answer 5

If it is positive you do extra testing to see what type of testing you are picking up. Other techniques include an:
- Immunoblots - seeing if an antibody binds to an antigen. You will then see a colour change in the line corresponding to the autoantibody present
- ELZA Tests
This helps clarify what you have picked up in the test
- Microbead-based immunoassay

Question 6

What is the likely diagnosis of the following case:

- 25 year old lady
Rheumatology clinic:
- 3 month history
- Patchy alopecia
- Painful and swollen joints of the hands
- Mouth ulcers

Bloods:

• Thrombocytopenia
• Raised Creatinine
• Positive ANA Screen
• Low C4 and C3 Complement

Answer 6

SLE

Question 7

What is the likely diagnosis for the following patient:

• 67 year old man
• Presents to GP with joint stiffness and pain mainly affecting the small joints of both hands.
• Stiffness worst in the morning and improves over 1-2 hours

Bloods:

• Thrombocytosis
• Positive for Rheumatoid factor
• raised CCP
• Joint X ray- peri-articular swelling with effusion of MCP joints, osteopenia, joint space narrowing and erosions
• CXR normal

Answer 7

Rheumatoid Arthritis

Question 8

How can we use Rhematoid factor in diagnostics?

Answer 8

• Antibody (IgM, IGG or OgA) directed against the Fc portion of IgG. It is antibody binding to another antibody
  
  • Commonly found in RA but also in other diseases and so not diagnostic of RA (sensitivity and specificity around 70%)
  • Can be seen in other diseases in which there is polyclonal stimulation of B cells e.g. chronic infection

Question 9

What is ACPA?

Answer 9

Anti-CCP Antibody

- In combination with RF. It is 95% specific and so more diagnostic of RA
- Useful as a prognostic marker 
- Positive patients tend to have more severe and erosive disease
- CCP antigen is part of some of the soft tissues

Question 10

What is cANA and pANA?

Answer 10

Patterns seen in ANA antibody testing. They suggest the antigen.

Question 11

What is the clinical utility of ANCA testing?

Answer 11

ANCA - Used in Vasculitis
Vasculitis can be very generalised and non-specific. These patterns slightly differentiate different types of Vasculitis.

ANCA testing is quite reliable. Vasculitis can be quite severe and can lead to end stage renal failure, affect the lungs or be fatal.

A positive ANCA is useful in suggesting the diagnosis is the proper clinical setting. You would then do a skin biopsy, kidney biopsy or even lung depending on where the signs have shown.

Question 12

How can we test for autoimmune liver disease?

Answer 12

• Part of non-invasive liver screen
  - Perform if liver tests deranged and you need to know if it is infective or autoimmune
  - Anti-mitochondrial Ab specific for primary biliary sclerosis
  - Anti-smooth muscle and anti-liver/kidney/microsomal (LKS) Abs, found in autoimmune hepatitis
  - Antibodies detected by IF screening using rodent tissue block (oesophagus, liver and kidney) and antigen specific ELISA
  Use different tissues to define which type of antibody is reacting to the particular antigen

Question 13

How can we test for type 1 diabetes using autoantibodies?

Answer 13

• Several types:
  • islet cell antibodies
  • anti-GAD65 anti-GAD67
  • anti-insulinoma antigen 2 (IA-2)
  • insulin autoantibodies (IAAs)
  - These antibodies disappear with progression of disease and total destruction of β islet cells
  - Disease confirmation
  Used to identify relatives and patients at risk of developing autoimmune diabetes

Question 14

What is the antigen in pernicious anaemia?

Answer 14

• Antigen: H+K+-ATPase located in the gastric parietal cells of rodent stomach.
  - Clinical Antibody present in more than 90% of patients with Pernicious anaemia.