Immunological Investigation of Autoimmune Disease Flashcards
The factors that contribute to autoimmune disease
Genetic components (HLA inheritance), Hormonal (higher female incidence), , environmental factors (infections, UV radiation and drugs), age, diets and trauma
Autoimmunity
A breakdown of immunological tolerance
Process of autoimmunity
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.
Spectrum of autoimmune diseases
Organ specific (hashimotos) to non-organ specific (SLE)
Performance characterisitcs of immunological testing
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
Immunology Tests
Antinuclear Antibodies Antineutrophil cytoplasmic antibodies Antiphospholipid antibodies Complement Cryoglobulins
Autoantibody production
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.
Antinuclear Antibodies (ANA)
- SLE
- Drug induced Lupus
- MCTD
- RA
- Sjogrens
- Scleroderma
- Dermatomysitis
- Old age
- Chronic inflammation
- Neoplasia
- CAH
- PBC
- Normality
Sensitivity of ANA in SLE
High sensitivity but low specificity. If the ANA test is negative, SLE is extremely unlikely.
Homogenous staining
Present where there are autoantibodies directed against chromosomal antibodies. dsDNA occurs in SLE, ssDNA is non-specific and histone proteins show drugs induced lupus
Speckled pattern staining
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
Nucleolar staining
Where autoantibodies are directed solely against nucleolar RNA. Occurs in scleroderma, systemic sclerosis and overlap syndromes.
Peripheral staining
Where staining is confided to the nuclear membrane. dsDNA occurs in SLE and autoimmune liver disease.
Disease monitoring
Immunological testing can also be useful in monitoring of disorders. Anti-dsDNA is one of them.
Disease sub-classification
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.
ANCA testing is useful in
Small vessel vasculitis. (ANCA associated vasculitis)
C-ANCA is found
Across the whole of the cytoplasm
P-ANCA is found
In the perinuclear antibody (around the nucleus)
C-ANCA (anti-proteinase 3)
Highly specific to Granulomatosis with Polyangitis and found in 60% of organ specific disease
P-ANCA (anti-myeloperoxidase)
This can be found in microscopic polyangitis and eosinophilic granulomatosis with polyangitis
When else can raised ANCA be present (Antinuclear Cytoplasmic Antibodies)
Infection, inflammation, drug use, connective tissue disorders and inflammatory bowel disease
Features of antiphospholipid syndrome
- Recurrent fetal loss
- Livedo reticularis
- Vascular Thrombosis
- Thrombocytopenia
What occurs in antiphospholipid syndrome
Antibodies are produced against bodies phospholipids
Anti-phospholipid antibodies
Anticardiolipin antibodies, AntiB2 glycoprotein I antibodies, lupus anticoagulant.
Complement system
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
Functions of the complement system
- Phagocyte Chemotaxis
- Opsonisation
- Lysis of micro-organisms
- Maintaining solubility of immune complexes
Complement deficiency
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).
Cryoglobulin Type 1
Monoclonal immunoglobulin associated with plasma cell dyscrasias, hepatitis C and HIV
Cryoglobulin type 2
Polyclonal IgG complexed with monoclonal IgM rheumatoid factor. Associated with Hepatitis C and HIV
Cryoglobulin type 3
Polyclonal immunoglobulins present in connective tissue disease
Cryoglobulins can be found in
- Livedo Reticularis
- Raynauds
- Peripheral cyanosis
- Purpura/Vasculitis
- Glomerulonephritis
- Neuropathy
- Arthralgia
- Thrombosis
- Haemorrhage
