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Autoimmune disease can be either organ-specific illnesses (eg, thyroid disease, type 1 diabetes mellitus, and myasthenia gravis (MG)) or systemic illnesses (eg, rheumatoid arthritis (RA) and 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, type 1 diabetes mellitus (DM), and 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 Sjögrens syndrome, SLE.
- Anti-LA: primary Sjögrens 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 (tTG), antigliadin and endomysial antibodies (EMAs):
- These are sensitive and specific for coeliac disease.
- IgA anti-tissue transglutaminase (tTG) are slowly replacing IgA EMAs 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.
- Antimitochondrial antibodies:
- 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:
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.
- Combined tests for autoantibodies to thyroglobulin and thyroid microsome antigens detect almost all goitrous thyroiditis (Hashimoto's disease), atrophic thyroiditis and about 70-90% of Graves' disease.
- Antithyroid microsomal antibodies may also be seen in patients with RA, Sjögren's syndrome, SLE and thyroid cancer.
- Antithyroid microsomal autoantibodies are found in about 6% of normal adults and their prevalence increases with age.
- Thyrotropin receptor antibodies:
- Useful in the diagnosis of Graves' disease but do not distinguish between stimulatory or inhibitory antibodies.
- Thyroid peroxidase antibodies:
- Seen in high titre in many patients with Hashimoto's thyroiditis but also seen in intermediate titre in 50-80% of patients with 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 MG.
- Antibodies in peripheral neuropathy:
- Neurological manifestations of malignancy:
Glomerular basement membrane (GBM) antibodies:
- Are detected in untreated 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 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 Wegener's granulomatosis.
Further reading & references
- Tan EM; Autoantibodies, autoimmune disease, and the birth of immune diagnostics. J Clin Invest. 2012 Nov 1;122(11):3835-6. doi: 10.1172/JCI66510. Epub 2012 Nov 1.
- Scofield RH; Autoantibodies as predictors of disease. Lancet. 2004 May 8;363(9420):1544-6.
- Oertelt S, Rieger R, Selmi C, et al; A sensitive bead assay for antimitochondrial antibodies: Chipping away at AMA-negative primary biliary cirrhosis. Hepatology. 2007 Mar;45(3):659-65.
- LaGasse JM, Brantley MS, Leech NJ, et al; Successful prospective prediction of type 1 diabetes in schoolchildren through multiple defined autoantibodies: an 8-year follow-up of the Washington State Diabetes Prediction Study. Diabetes Care. 2002 Mar;25(3):505-11.
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.
Dr Colin Tidy
Dr Colin Tidy
Dr Adrian Bonsall