Immunological Investigation of Autoimmune Disease

Question 1

The factors that contribute to autoimmune disease

Answer 1

Genetic components (HLA inheritance), Hormonal (higher female incidence), , environmental factors (infections, UV radiation and drugs), age, diets and trauma

Question 2

Autoimmunity

Answer 2

A breakdown of immunological tolerance

Question 3

Process of autoimmunity

Answer 3

Tolerance is broken down and there is a recognition of self (termed pathological autorecognition) resulting in the activation of T cells and B cells. This results in inflammation and tissue damage.

Question 4

Spectrum of autoimmune diseases

Answer 4

Organ specific (hashimotos) to non-organ specific (SLE)

Question 5

Performance characterisitcs of immunological testing

Answer 5

Accuracy
Precision
Sensitivity
Specificity
Predictive Value
Purpose for which the test is used

THESE CHARACTERISTICS DECIDE THE VALUE OF THE TEST. THESE ARE DIVERSE AND DEPEND ON THE PATIENT AND THE SITUATION

Question 6

Immunology Tests

Answer 6

Antinuclear Antibodies
Antineutrophil cytoplasmic antibodies
Antiphospholipid antibodies
Complement
Cryoglobulins

Question 7

Autoantibody production

Answer 7

Autoantibodies are produced by B-cells which are triggered by T-cell recognition of an antigen (sub-population of T-helper cells which drive most antibody production). The problem with autoimmune disease in which autoantibodies are included are due to issues with T-cells. These are usually IgG. This IgG can play a role in the causation of the disease, however, lots are biproducts of another underlying pathology. They are good markers of disease.

Question 8

Antinuclear Antibodies (ANA)

Answer 8

• SLE
• Drug induced Lupus
• MCTD
• RA
• Sjogrens
• Scleroderma
• Dermatomysitis
• Old age
• Chronic inflammation
• Neoplasia
• CAH
• PBC
• Normality

Question 9

Sensitivity of ANA in SLE

Answer 9

High sensitivity but low specificity. If the ANA test is negative, SLE is extremely unlikely.

Question 10

Homogenous staining

Answer 10

Present where there are autoantibodies directed against chromosomal antibodies. dsDNA occurs in SLE, ssDNA is non-specific and histone proteins show drugs induced lupus

Question 11

Speckled pattern staining

Answer 11

Autoantibodies are directed against non-chromosomal nuclear proteins. Ro occurs in Sjogrens, La occurs in Sjogrens, Sm occurs in SLE, RNP occurs in MCTD, Scl-70 occurs in scleroderma, Jo-1 occurs in polymyositis, centromere occurs in CREST, scleroderma, MCTD and SLE

Question 12

Nucleolar staining

Answer 12

Where autoantibodies are directed solely against nucleolar RNA. Occurs in scleroderma, systemic sclerosis and overlap syndromes.

Question 13

Peripheral staining

Answer 13

Where staining is confided to the nuclear membrane. dsDNA occurs in SLE and autoimmune liver disease.

Question 14

Disease monitoring

Answer 14

Immunological testing can also be useful in monitoring of disorders. Anti-dsDNA is one of them.

Question 15

Disease sub-classification

Answer 15

As well as diagnosis and disease monitoring the pattern of autoantibodies which a patient produces can be used to predict known sub-classifications or complications of disease. Anti-dsDNA predicts nephritis and vasculitis, Anti-SM predicts nephritis and cerebral disease.

Question 16

ANCA testing is useful in

Answer 16

Small vessel vasculitis. (ANCA associated vasculitis)

Question 17

C-ANCA is found

Answer 17

Across the whole of the cytoplasm

Question 18

P-ANCA is found

Answer 18

In the perinuclear antibody (around the nucleus)

Question 19

C-ANCA (anti-proteinase 3)

Answer 19

Highly specific to Granulomatosis with Polyangitis and found in 60% of organ specific disease

Question 20

P-ANCA (anti-myeloperoxidase)

Answer 20

This can be found in microscopic polyangitis and eosinophilic granulomatosis with polyangitis

Question 21

When else can raised ANCA be present (Antinuclear Cytoplasmic Antibodies)

Answer 21

Infection, inflammation, drug use, connective tissue disorders and inflammatory bowel disease

Question 22

Features of antiphospholipid syndrome

Answer 22

• Recurrent fetal loss
• Livedo reticularis
• Vascular Thrombosis
• Thrombocytopenia

Question 23

What occurs in antiphospholipid syndrome

Answer 23

Antibodies are produced against bodies phospholipids

Question 24

Anti-phospholipid antibodies

Answer 24

Anticardiolipin antibodies, AntiB2 glycoprotein I antibodies, lupus anticoagulant.

Question 25

Complement system

Answer 25

1) collection of serum proteins organised into a classical pathway, an alternate pathway and a terminal pathway,
2) control proteins in the serum and body fluids which prevent inappropriate complement activation or downregulate and turn off complement activation and 3) a series of cell surface control proteins which again control and regulate the activity of the complement pathway

Question 26

Functions of the complement system

Answer 26

• Phagocyte Chemotaxis
• Opsonisation
• Lysis of micro-organisms
• Maintaining solubility of immune complexes

Question 27

Complement deficiency

Answer 27

Genetic deficiencies of components in the three main parts of the complement system present in characteristic, but different, ways. Alternate and terminal pathways present with infections. Deficiencies of classical pathway components characteristically presents as lupus-like systemic immune complex disease (although some patients also get recurrent infections).

Question 28

Cryoglobulin Type 1

Answer 28

Monoclonal immunoglobulin associated with plasma cell dyscrasias, hepatitis C and HIV

Question 29

Cryoglobulin type 2

Answer 29

Polyclonal IgG complexed with monoclonal IgM rheumatoid factor. Associated with Hepatitis C and HIV

Question 30

Cryoglobulin type 3

Answer 30

Polyclonal immunoglobulins present in connective tissue disease

Question 31

Cryoglobulins can be found in

Answer 31

• Livedo Reticularis
• Raynauds
• Peripheral cyanosis
• Purpura/Vasculitis
• Glomerulonephritis
• Neuropathy
• Arthralgia
• Thrombosis
• Haemorrhage