Autoantibody

Healthy individuals normally either do not have autoantibodies or have them at a very low titer, and a change or rise can signify the development of cancer or another disease state. A number of cancer antigens have been investigated for their ability to induce detectable autoantibodies, including p53, MUCl, c-myc, and c-erbB-2. For example, accumulation of mutant p53 proteins within tumor cells may lead to the development of autoantibodies. Nine percent to 48% of primary breast cancer patients have detectable anti-p53 antibodies, as do 11% to 64% of lung cancer patients. Anti-p53 antibodies have also been detected in hepatocellular, bladder, colorectal, gastric, and other cancers.  

Many cancers are heterogeneous, and do not consistently express tumor markers. It is clear that no single tumor marker will detect aU cancers. Therefore the detection of multiple antigens should increase the sensitivity of detection. This is also the pase with autoantibody detection. Using a single auto antibody the detection of primary breast cancer was between 35% and 47% however using four autoantibodies (p53, MUCl, c-rayc, and c-erbB-2) the sensitivity can be increased to 82%.  

Autoantibodies are also useful in prognosis and monitoring of disease. Elevated levels of autoantibodies to p53 are associated with a poor prognosis, independent of the tumor-related antigens. This may be due to the fact that expression of the tumor antigen at a distant and/or abnormal site triggers an immune response. The titer of the autoantibodies also tends to follow the amount of tumor antigen, which 

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An increasing number of diseases are known to be linked to defects in receptor stmcture, function, or coupling. The defects may He at several locations in the stmcture of the receptor, which may alter its abiHty either to bind dmgs, to be inserted into the membrane, or to couple to effectors (including G-proteins) in the coupling protein or in the presence of autoantibodies, which can proceed to activate, block, or lyse the receptors and its components (96—99). 

Autoantibodies are directed against nicotinic acetylcholine receptors in myasthenia gravis, resulting in receptor loss, skeletal muscle paralysis, and dysfunction (100). In addition, antibodies directed against voltage-gated Ca " channels produce similar neuromuscular dysfunction of Lambert-Eaton... 

Also, the outcome covers a large spectrum. Autoantibodies can specifically block an important protein (such as the gastric intrinsic factor required for the uptake of orally taken vitamin B12), or the receptor for —> acetylcholine (as in myasthenia gravis), but also can... 

The treatment of an autoimmune disease very much depends on the nature of the clinical outcome it causes. Although the formation of autoantibodies causes the inactivation of the gastric intrinsic factor, the subsequent shortage of vitamin B12 can be easily overcome by supplying it via an parenteral route. Lifelong immunosuppression (with all its side effects) thus is inappropriate. When, however, as in sympathetic ophtalmia, after damage of the first eye the second eye is endangered, an even drastic immunosuppression is mandatory. 

Recoverin is aberrantly expressed in malignant tumors localized outside the nervous system. This was found to trigger the immune system resulting in the production of autoantibodies inducing the degeneration of the retina. 

Isaacs syndrome (an acquired neuromyotonia) is caused by autoantibodies directed against 4-aminopyr-idine or a-dendrotoxin-sensitive K+ channels (Kvl.l and Kvl.6) in motor and sensory neurons. The syndromes include muscle twitching during rest, cramps during muscle contraction, impaired muscle relaxation, and muscle weakness due to hyperexcitability of peripheral motor nerves. 

It is an autoantibody whose autoantigen is the Fc portion of IgG. Rheumatoid factors may be of any immunoglobulin isotype but it is IgM rheumatoid factor that is commonly measured in rheumatoid arthritis. Classification criteria for rheumatoid arthritis include only one serological test, namely rheumatoid factor. However, it is not diagnostic test rather it may be confirmatory when a number of other clinical features are present. 

Matthews, R.C., Bumie, J.P., Howat, D., Rowland, T., Walton. F. (1991). Autoantibody to heat shock protein 90 can mediate protection against systemic candidosis. Immunology 74,20-24. 

Alsenz J, Bork K, Loos M Autoantibody-mediated acquired deficiency of Cl inhibitor. N Engl J Med 1987 316 1360-1366. 

Jackson J, Sim R, Whelan A, Feighery C An IgG autoantibody which inactivates Cl-inhibitor. Nature 1986 323 722-724. 

Jackson J. Sim R. Whaley K, Feighery C Autoantibody facilitated cleavage of Cl-inhibitor in autoimmune angioedema. J Chn Invest 1989 83 698-707. He S. Sim R. Whaley K Mechanism of action of anti-Cl-inhibitor autoantibodies prevention of the formation of stable Cls-Cl-inh complexes. Mol Med 1998 4 119-128. 

Hide M, Francis DM, Grattan CEH, Hakimi J, Kochan JP, Greaves MW Autoantibodies against the high-affinity IgE receptor as a cause of histamine release in chronic urticaria. N Engl J Med 1993 328 1599. Sd... 

Breakdown of tolerance mechanisms. There are at least two mechanisms for maintaining unresponsiveness to self The first is by specific deletion of self-reactive clones and the second by suppression. A failure of either of these two may result in an autoimmune disease. In normal, healthy individuals, antigen-binding, self-reactive B cells and the resultant low litres of autoantibodies are not uncommon. The origin of the self-reactive B cells is not clear, but there are four ways in which they may become activated. 

Types of autoimmune diseases vary widely, from organ-specific diseases such as thyroiditis where there may be stimulation (thyrotoxicosis) by antibody against the receptor for pituitary thyroid-stimulating hormone (TSH) or inhibition (myxoedema) by cell destruction probably mediated by NK cells and autoantibody, through to non-... 

Cells possess surface receptor sites for the chemical messengers of the body. Should an autoantibody be produced against this site, it can combine with it and cause the same effect as the chemical messenger, e.g. thyrotoxicosis caused by autoantibody to the receptor site to TSH as previously described (section 4.10). 

SALONEN J T, YLA-HERTTUALA S, YAMAMOTO R, BUTLER S, KORPELA H, SALONEN R, NYYSSONEN K, PALiNSKi w, wiTZTUM J L (1992) Autoantibody against oxidised LDL and progression of carotid atherosclerosis, Lancet, 339, 883-7. 

Iribarren, C. et al.. Association of serum vitamin levels, LDL susceptibility to oxidation, and autoantibodies against MDA-LDL with carotid atherosclerosis a case-control %Vady, Arterioscler. Thromb. Vase. Biol, 17, 1171, 1997. 

El-Fawal HA, Gong Z, Little AR, Evans HL. 1996. Exposure to methyl mercury results in serum autoantibodies to neurotypic and ghotypic proteins. Neurotoxicology 17 267-276. 

Autoantibodies against oxidized LDL have been demonstrated in the plasma of patients and hyper-cholesterolaemic animals (Palinski et al., 1989 Mitchinson et al., 1988). 

Antibodies to very low density lipoprotein (VLDL) and LDL have been detected in the serum of patients with RA, but not control groups (Lazarevic et al., 1993). In these studies, 38% of patients with active RA tested positive for anti-VLDL/LDL antibodies whilst these autoantibodies were not detected in patients with psoriatic arthritis, osteoarthritis or healthy subjects. Lipoproteins were found in the dissociated components of circulating immune complexes in the serum of 30% of the RA patients. It was concluded that dyslipoproteinaemia in some RA patients may be due to an autoimmune component of the disease. 

Autoantibodies to cardiolipin, which cross-react with... 

NAAb Natural autoantibody NAb Natural antibody NAC N-acetylcysteine NADH Reduced nicotinamide adenine dinucleotide NADP Nicotinamide adenine diphosphate... 

B cells likely cross previously damaged sections of the blood-brain barrier to arrive in the CNS, an area normally free of B cells. Autoreactive T cells cause B cells to form autoantibodies to myelin. B-cell antibodies also initiate the complement cascade which causes myelin degradation.7... 

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