An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies.

Production

Antibodies are produced by B cells in two ways: (i) randomly, and (ii) in response to a foreign protein or substance within the body. Initially, one B cell produces one specific kind of antibody. In either case, the B cell is allowed to proliferate or is killed off through a process called clonal deletion. Normally, the process of central tolerance and peripheral tolerance eliminates and suppresses B cells which are able to recognize the body's own healthy proteins, cells and tissues, preventing the development of autoimmune disease. Sometimes, the immune system ceases to recognize one or more of the body's normal constituents as "self", leading to production of pathological autoantibodies. Autoantibodies may also play a nonpathological role; for instance they may help the body to destroy cancers and to eliminate waste products. The role of autoantibodies in normal immune function is also a subject of scientific research.

Cause

The causes of autoantibody production are varied and not well understood. It is thought that some autoantibody production is due to a genetic predisposition combined with an environmental trigger, such as a viral illness or a prolonged exposure to certain toxic chemicals. There is generally not a direct genetic link however.

While families may be susceptible to autoimmune conditions, individual family members may have different autoimmune disorders, or may never develop an autoimmune condition. Researchers believe that there may also be a hormonal component as many of the autoimmune conditions are much more prevalent in women of childbearing age. While the initial event that leads to the production of autoantibodies is still unknown, there is a body of evidence that autoantibodies may have the capacity to maintain their production.

Diseases

The type of autoimmune disorder or disease that occurs and the amount of destruction done to the body depends on which systems or organs are targeted by the autoantibodies, and how strongly. Disorders caused by organ specific autoantibodies, those that primarily target a single organ, (such as the thyroid in Graves' disease and Hashimoto's thyroiditis), are often the easiest to diagnose as they frequently present with organ related symptoms. Disorders due to systemic autoantibodies can be much more elusive. Although the associated autoimmune disorders are rare, the signs and symptoms they cause are relatively common. Symptoms may include: arthritis-type joint pain, fatigue, fever, rashes, cold or allergy-type symptoms, weight loss, and muscular weakness. Associated conditions include vasculitis which are inflammation of blood vessels and anemia. Even if they are due to a particular systemic autoimmune condition, the symptoms will vary from person to person, vary over time, vary with organ involvement, and they may taper off or flare unexpectedly. Add to this the fact that a person may have more than one autoantibody, and thus have more than one autoimmune disorder, and/or have an autoimmune disorder without a detectable level of an autoantibody, complicating making a diagnosis.

Examples of autoimmune diseases illustrate how autoantibodies can cause tissue-specific damage through different mechanisms. One example is Rheumatoid arthritis, an autoimmune disease in which the immune system produces autoantibodies that attack the body’s own joint tissues . Environmental factors, such as infections or inhaled irritants, can change the body’s proteins, leading to their recognition as foreign and the production of autoantibodies. These triggers then lead to the release of inflammatory molecules that recruit immune cells to the lining of the joints, where they begin to damage cartilage and bone. This explains why rheumatoid arthritis is typically a long-term, progressively worsening condition. This results in skin cells losing the ability to remain attached to one another, leading to the separation of skin layers and the formation of fragile blisters. Different forms of pemphigus affect different proteins. For instance, pemphigus foliaceus targets proteins in the upper layers of the skin, often leading to superficial blisters that rupture easily and leave behind crusted or scaly skin

List of some autoantibodies and commonly associated diseases

Note: the sensitivity and specificity of various autoantibodies for a particular disease is different for different diseases.

{| class="wikitable"

!colspan=2| Autoantibody !! Antibody target !! Condition

|-

|rowspan=12| Antinuclear antibodies

| Anti-SSA/Ro autoantibodies ||rowspan=2| ribonucleoproteins || systemic lupus erythematosus, neonatal heart block, primary Sjögren syndrome

|-

| Anti-La/SS-B autoantibodies || Primary Sjögren syndrome

|-

| Anti-centromere antibodies || centromere || CREST syndrome

|-

| Anti-dsDNA || double-stranded DNA || SLE

|-

| Anti-Jo1 || histidine-tRNA ligase || inflammatory myopathy

|-

| Anti-RNP || Ribonucleoprotein || Mixed connective tissue disease

|-

| Anti-Smith || snRNP core proteins || SLE

|-

| Anti-topoisomerase antibodies || Type I topoisomerase || systemic sclerosis (anti-Scl-70 antibodies)

|-

| Anti-histone antibodies || histones || SLE and drug-induced LE

|-

| Anti-p62 antibodies || Sp100 nuclear antigen

|-

| Anti-glycoprotein-210 antibodies || nucleoporin 210kDa

|-

|rowspan=2| Anti-transglutaminase antibodies || Anti-tTG || || celiac disease

|-

| Anti-eTG || || dermatitis herpetiformis

|-

|rowspan=3 colspan=2| Anti-ganglioside antibodies || ganglioside GQ1B || Miller Fisher syndrome

|-

| ganglioside GD3 || acute motor axonal neuropathy (AMAN)

|-

| ganglioside GM1 || multifocal motor neuropathy with conduction block (MMN)

|-

|colspan=2| Anti-actin antibodies || actin || Coeliac disease (antibody levels correlate with the level of intestinal damage), autoimmune hepatitis, gastric cancer

|-

|colspan=2| anti-CCP || cyclic citrullinated peptide || rheumatoid arthritis

|-

|colspan=2| Liver kidney microsomal type 1 antibody || || autoimmune hepatitis

|-

| Lupus anticoagulant || Anti-thrombin antibodies || thrombin || systemic lupus erythematosus

|-

|colspan=2| Antiphospholipid antibodies || phospholipid || antiphospholipid syndrome

|-

|rowspan=2| Anti-neutrophil cytoplasmic antibody || c-ANCA || proteins in neutrophil cytoplasm || granulomatosis with polyangiitis

|-

| p-ANCA || neutrophil perinuclear || microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, systemic vasculitides (non-specific)

|-

|colspan=2| Rheumatoid factor || IgG || rheumatoid arthritis

|-

|colspan=2| Anti-smooth muscle antibody || smooth muscle || chronic autoimmune hepatitis

|-

|colspan=2| Anti-mitochondrial antibody || mitochondria || primary biliary cirrhosis

|-

|colspan=2| Anti-SRP || signal recognition particle || dermatomyositis

|-

|colspan=2| || exosome complex || scleromyositis

|-

|colspan=2| Anti-AChR || nicotinic acetylcholine receptor || myasthenia gravis

|-

|colspan=2| Anti-MUSK || Muscle-specific kinase (MUSK) || myasthenia gravis

|-

|colspan=2| Anti-VGCC || voltage-gated calcium channel (P/Q-type) || Lambert–Eaton myasthenic syndrome

|-

|colspan=2| Anti-Vinculin || vinculin ||small intestinal bacterial overgrowth

|-

|rowspan=3|Anti-thyroid autoantibodies|| Anti-TPO antibodies || Thyroid peroxidase (microsomal) || Hashimoto's thyroiditis, Graves' disease

|-

|Anti-thyroglobulin antibodies (TgAbs) || Thyroglobulin || Hashimoto's thyroiditis

|-

|Anti-thyrotropin receptor antibodies (TRAbs) || TSH receptor || Graves' disease

|-

|colspan=2| Anti-Hu (ANNA-1) || Neuronal nuclear proteins || paraneoplastic cerebellar degeneration, limbic encephalitis, encephalomyelitis, subacute sensory neuronopathy, choreathetosis

|-

|colspan=2| Anti-Yo || Cerebellar Purkinje cells || paraneoplastic cerebellar degeneration

|-

|colspan=2| Anti-Ma || || encephalomyelitis, limbic encephalitis

|-

|colspan=2| Anti-Ri (ANNA-2) || Neuronal nuclear proteins|| opsoclonus myoclonus syndrome

|-

|colspan=2| Anti-Tr || glutamate receptor || paraneoplastic cerebellar syndrome

|-

|colspan=2| Anti-amphiphysin || amphiphysin || stiff person syndrome, paraneoplastic cerebellar degeneration

|-

|colspan=2| Anti-GAD || Glutamate decarboxylase || stiff person syndrome, diabetes mellitus type 1

|-

|colspan=2| Anti-VGKC || voltage-gated potassium channel (VGKC) || limbic encephalitis, Isaac's Syndrome (autoimmune neuromyotonia)

|-

|colspan=2| Anti-CRMP-5 || Collapsin response mediator protein 5 || optic neuropathy, chorea

|-

|colspan=2| || basal ganglia neurons || Sydenham's chorea, paediatric autoimmune neuropsychiatric disease associated with Streptococcus (PANDAS)

|-

|colspan=2| Anti-NMDAr || N-methyl-D-aspartate receptor (NMDA) || anti-NMDA receptor encephalitis

|-

|colspan=2| NMO antibody || aquaporin-4 || neuromyelitis optica (Devic's syndrome)

|-

| colspan="2" |Anti-desmoglein (anti-desmosome)

|Dsg3 (Desmoglein 3) and sometimes Dsg1

|Pemphigus vulgaris

|-

| colspan="2" |Anti-hemidesmosome

|hemidesmosomes

|Bullous pemphigoid

|-

| colspan="2" |Anti-glomerular basement membrane

|basement membrane in lungs and kidneys

|Goodpasture syndrome

|-

| colspan="2" |Anti-parietal cell

|gastric parietal cells

|Pernicious anemia

|-

| colspan="2" |Anti-intrinsic factor

|intrinsic factor

|Pernicious anemia

|-

| colspan="2" |Anti-phospholipase A2 receptor

|phospholipase A2 receptor

|Membranous nephropathy

|}

See also

  • Anti-glutamate receptor antibodies
  • Reference ranges for blood tests#Autoantibodies
  • Paraneoplastic syndrome

References

  • Autoimmunity – an Introduction Industrial Learning Unit on Chemgaroo
  • Autoimmunityblog - summaries of research articles + glossary terms
  • Detection of autoantibodies with self-assembling radiolabeled antigen tetramers (a protocol)
  • Antibody Sensors