Autoimmune disease can be either organ-specific illnesses (eg, thyroid disease, type 1 diabetes mellitus, myasthenia gravis) or systemic illnesses (eg, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE)). The cause of autoimmune damage may be mainly due to either autoantibodies or autoimmune T lymphocytes. Nearly all autoimmune diseases are associated with circulating autoantibodies, which may also be found associated with non-related illnesses and in healthy individuals.
The immune system is able to identify cellular factors that initiate tumour formation by making autoantibodies to tumour-associated antigens - eg, novel autoantibodies have been detected during the transition period to hepatocellular carcinoma In a patient with liver cirrhosis.
Autoantibodies are often detected many years before the onset of disease.
- Antinuclear factor (ANF):
- Raised ANF is almost always present in SLE.
- It is also associated with drug-induced lupus erythematosus (LE), systemic sclerosis (scleroderma), Sjögren's syndrome, polymyositis and dermatomyositis, mixed connective tissue disorder and autoimmune hepatitis.
- Drugs associated with drug-induced LE are isoniazid, phenytoin, hydralazine, methyldopa, chlorpromazine, penicillamine and minocycline.
- Raised ANF may also be seen in Addison's disease, idiopathic thrombocytopenic purpura (ITP), Hashimoto's thyroiditis, autoimmune haemolytic anaemia and type 1 diabetes mellitus; occasionally a positive ANF is found in normal elderly people.
- Single-stranded DNA antibody: 70% of patients with SLE but also in other autoimmune rheumatic and inflammatory conditions, and is therefore of limited clinical value.
- Anti-double stranded DNA antibody (anti-dsDNA): associated with SLE. It is a less sensitive but more specific test than ANF and is rarely positive in other conditions. It correlates with disease activity.
- Anti-histone antibodies: associated with SLE and drug-induced LE.
- Anti-Sm (Smith): very specific but relatively insensitive for SLE. It is associated with central nervous system involvement and nephritis in SLE.
- Anti-RNP: mixed connective tissue disease. It is specific for SLE but lacks sensitivity. Anti-RNP is also associated in a minority of patients with systemic sclerosis and scleroderma.
- Anti-Ro: primary Sjögren's syndrome, SLE.
- Anti-LA: primary Sjögren's syndrome, SLE.
- Centromere: scleroderma, systemic sclerosis.
- Nucleolar RNA: systemic sclerosis.
- Scl-70: diffuse cutaneous systemic sclerosis (dcSSc).
- PM/Scl: polymyositis, systemic sclerosis overlap syndrome.
- Jo-1 (an aminoacyl-tRNA synthetase antibody): dermatomyositis.
- Ribosomal-P: SLE (often in absence of anti-DsDNA antibodies).
- Rheumatoid factor is a significant serological marker for RA but is a poor marker for monitoring disease.
- High levels are associated with RA and Sjögren's syndrome.
- Other disease associations include chronic hepatitis, chronic viral infection, tuberculosis, leprosy, leukaemia, dermatomyositis, infectious mononucleosis, systemic sclerosis and SLE.
- IgM rheumatoid factor is found in 2-10% of healthy adults.
- Anticardiolipin antibodies are the most commonly detected antiphospholipid antibodies.
- Anticardiolipin antibodies are associated with primary antiphospholipid syndrome. They are also present in some patients with SLE.
- IgG anticardiolipin antibodies are more significant than IgM anticardiolipin antibodies.
Intrinsic factor antibodies
Very specific and virtually diagnostic for pernicious anaemia but sensitivity is only 40-75%.
Parietal cell antibodies
- Associated with autoimmune gastritis but are also found in pernicious anaemia, autoimmune hepatitis and chronic liver disease.
- Parietal cell antibodies may also be found in elderly patients without autoimmune disease.
IgA anti-tissue transglutaminase (anti-tTG), antigliadin and endomysial antibodies (EMAs)
- These are sensitive and specific for coeliac disease.
- IgA EMAs are slowly being replaced by IgA anti-tTG as the method of choice for screening for coeliac disease (high sensitivity and specificity for both coeliac disease and dermatitis herpetiformis).
- tTG is an intracellular enzyme which is the major autoantigen of anti-endomysial antibodies (anti-EMAs). The IgG equivalents of these tests are less specific and sensitive but may be present if the patient has IgA deficiency, which can be associated with coeliac disease.
- May be present in primary biliary cirrhosis (95% of patients), autoimmune hepatitis, other causes of cirrhosis, RA, syphilis, SLE and thyroiditis.
- There are several different types of mitochondrial antibodies (MAs):
- M2 antimitochondrial antibodies (AMAs) are found in primary biliary cirrhosis.
- M1 is associated with syphilis.
- M2 and M3 are associated with primary biliary cirrhosis.
- M6 is associated with isoniazid-induced hepatitis.
Anti-smooth muscle antibodies
- High titres are found in 95% of patients with autoimmune active hepatitis.
- May also be found with primary biliary cirrhosis, primary sclerosing cholangitis, infectious mononucleosis, primary pulmonary hypertension and 3% of healthy individuals.
Antibodies in diabetes mellitus
- Glutamic acid decarboxylase (GAD) antibody.
- Islet cell antibody: prevalence at diagnosis is 75%, first-degree relatives 2-5% and the general population 0.4%.
- Insulin antibody: present in 40% of newly diagnosed type 1 diabetes mellitus. Titres of both islet cell and insulin antibody diminish once beta cell destruction is advanced and are not usually detected after the first year of disease.
Raised levels of antibodies against thyroid peroxidase, thyroglobulin and TSH receptor are commonly found in autoimmune thyroid disease.
- Thyrotropin receptor antibodies:
- Useful in the diagnosis of Graves' disease but do not distinguish between stimulatory or inhibitory antibodies.
- Thyroid peroxidase antibodies:
- The presence of anti-TPO antibodies is a hallmark of autoimmune thyroid disease, especially Hashimoto's thyroiditis, but also being highly prevalent in postpartum thyroiditis and Graves' disease.
Specific and characteristic of immunological infertility.
Steroid cell antibodies
Present in Addison's disease and autoimmune gonadal failure.
- Myasthenia gravis:
- Acetylcholine receptor antibody is associated in most patients with myasthenia gravis.
- Antibodies in peripheral neuropathy:
- Ganglioside M1 (GM1): patients with multifocal motor neuropathy and less frequently in Guillain-Barré syndrome (GBS).
- Antibodies to myelin-associated glycoproteins in multiple sclerosis, myasthenia gravis and SLE.
- Neurological manifestations of malignancy:
- Enteric neuronal antibodies: small cell carcinoma of bronchus.
- Antineuronal nuclear antibodies (ANNA): small cell carcinoma of lung, carcinoma of breast.
- Purkinje cell antibodies: gynaecological cancer, Hodgkin's disease.
- Retinal antibodies: small cell carcinoma of lung.
- Anti-glomerular basement membrane (GBM) antibodies are detected in Goodpasture's syndrome.
- They may also co-exist with antineutrophil cytoplasmic antibody (ANCA) in patients with systemic vasculitis and rapidly progressive glomerulonephritis (RPGN).
- Concentration of GBM antibodies can be used to monitor the patient's response to therapy.
Antineutrophil cytoplasmic antibodies
- ANCA: associated with necrotising vasculitis and vasculitis associated with rheumatic and inflammatory bowel disease.
- There are two major types of indirect immunofluorescence staining:
- C-ANCA (cytoplasmic): associated with granulomatosis with polyangiitis (Wegener's granulomatosis), micropolyarterits, Churg-Strauss syndrome, polyarteritis nodosa and RPGN.
- P-ANCA (perinuclear): associated with microscopic polyangiitis, Churg-Strauss syndrome, anti-GBM disease, crescenteric glomerulonephritis and granulomatosis with polyangiitis (Wegener's granulomatosis).
Cardiac muscle antibodies are associated with heart failure, myocarditis and dilated cardiomyopathy.
- Intra-epidermal/desmosome antibody (pemphigus antibody) is associated with all forms of pemphigus.
- Basement membrane zone antibody (pemphigoid antibody) is associated mainly with bullous pemphigoid.
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