Autoimmune disease

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Autoimmune diseases
Classification and external resources
Specialty Rheumatology, gastroenterology
ICD-10 D84.9, M35.9
ICD-9-CM 279.4
OMIM 109100
DiseasesDB 28805
MedlinePlus 000816
MeSH D001327

An autoimmune disease is a pathological state arising from an abnormal immune response of the body to substances and tissues that are normally present in the body.

Autoimmunity, on the other hand, is the presence of self-reactive immune response (e.g., auto-antibodies, self-reactive T-cells), with or without damage or pathology resulting from it.[1] This may be restricted to certain organs (e.g. in autoimmune thyroiditis) or involve a particular tissue in different places (e.g. Goodpasture's disease which may affect the basement membrane in both the lung and the kidney).

The treatment of autoimmune diseases is typically with immunosuppression—medication that decreases the immune response. New novel treatments include Cytokine blockade (or the blockade of cytokine signaling pathways), removal of effector T-cells and B-cells (e.g. anti-CD20 therapy can be effective at removing instigating B-cells).[1] Intravenous Immunoglobulin has been helpful in treating some antibody mediated autoimmune diseases as well, possibly through negative feedback mechanisms.[2]

There are at least 80 types of autoimmune diseases are recognized. A major understanding of the underlying pathophysiology of autoimmune diseases has been the application of genome wide association scans that have identified a striking degree of genetic sharing among the autoimmune diseases.[3]

Definition[edit]

For a disease to be regarded as an autoimmune disease it needs to answer to Witebsky's postulates (first formulated by Ernest Perez and colleagues in 1957 and modified in 1994):[4][5]

  • Direct evidence from transfer of disease-causing antibody or disease-causing T lymphocyte white blood cells
  • Indirect evidence based on reproduction of the autoimmune disease in experimental animals
  • Circumstantial evidence from clinical clues
  • Genetic evidence suggesting "clustering" with other autoimmune diseases
  • Autoimmune diseases are incurable

Effects[edit]

Autoimmune diseases have a wide variety of different effects. They do tend to have one of three characteristic pathological effects which characterize them as autoimmune diseases:[6]

  1. Damage to or destruction of tissues
  2. Altered organ growth
  3. Altered organ function

It has been estimated that autoimmune diseases are among the leading causes of death among women in the United States in all age groups up to 65 years.[7]

A substantial minority of the population suffers from these diseases, which are often chronic, debilitating, and life-threatening.[citation needed]

There are more than 80 illnesses caused by autoimmunity.[8] Autoimmune diseases affect approximately 2-5% of the western world's population. Women are found to be more commonly affected than men. Environmental events can trigger some cases of autoimmune diseases such as exposure to radiation or certain drugs which can damage tissues of the body. Infection can also be a trigger of some autoimmune diseases for example Lupus which is thought to be a milder version of an idiopathic disorder where there is an increased production of antihistone antibodies.[7]

Pathophysiology[edit]

The human immune system typically produces both T-cells and B-cells that are capable of being reactive with self-antigens, but these self-reactive cells are usually either killed prior to becoming active within the immune system, placed into a state of anergy (silently removed from their role within the immune system due to over-activation), or removed from their role within the immune system by regulatory cells. When any one of these mechanisms fail, it is possible to have a reservoir of self-reactive cells that become functional within the immune system. The mechanisms of preventing self-reactive T-cells from being created takes place through Negative selection process within the thymus as the T-cell is developing into a mature immune cell.

Some infections, such as Campylobacter jejuni, have antigens that are similar (but not identical) to our own self-molecules. In this case, a normal immune response to C. jejuni can result in the production of antibodies that also react to a lesser degree with receptors on skeletal muscle (i.e., Myasthenia gravis).

There are many theories as to how an autoimmune disease state arises. Some common ones are listed below.

Cryptic determinants/molecular sequestration[edit]

Although it is possible for a potential auto antigen to be geographically sequestered in an immune privileged site within the body (e.g. the eye), mechanisms exist to express even these antigens in a tolerogenic fashion to the immune system. However, it is impossible to induce tolerance (immune unresponsiveness) to all aspects of an autoantigen. This is because under normal physiologic conditions some regions of a self-antigen are not expressed at a sufficient level to induce tolerance. These poorly displayed areas of an antigen are called "cryptic determinants." The immune system maintains a high-affinity repertoire to the cryptic self because the presentation of these determinants was insufficient to induce strong tolerance.[9]

Molecular mimicry[edit]

The concept of molecular mimicry describes a situation in which a foreign antigen can initiate an immune response in which a T or B cell component cross-recognizes self. The cross reactive immune response is responsible for the autoimmune disease state.[10] Cross-reactive immune responses to self were first described for antibodies.

Altered glycan theory[edit]

According to this theory the effector function of the immune response is mediated by the glycans (polysaccharides) displayed by the cells and humoral components of the immune system. Individuals with autoimmunity have alterations in their glycosylation profile such that a proinflammatory immune response is favored. It is further hypothesized that individual autoimmune diseases will have unique glycan signatures.[11]

Prevalence[edit]

The first estimate of US prevalence for autoimmune diseases as a group was published in 1997 by Jacobson, et al. They reported US prevalence to be around 9 million, applying prevalence estimates for 24 diseases to a US population of 279 million.[12] Jacobson's work was updated by Hayter & Cook in 2012.[13] This study used Witebsky's postulates, as revised by Rose & Bona,[14] to extend the list to 81 diseases and estimated overall cumulative US prevalence for the 81 autoimmune diseases at 5.0%, with 3.0% for males and 7.1% for females. The estimated community prevalence, which takes into account the observation that many people have more than one autoimmune disease, was 4.5% overall, with 2.7% for males and 6.4% for females. Based on a US population of 320 million,[15] the Hayter & Cook data indicate US prevalence at about 14.5 million.

In a report to the US Congress, the National Institutes of Health reported prevalence between 14.7 and 23.5 million.[16] Although the NIH report predates the Hayter & Cook study by 7 years, the NIH low-range number closely matches their estimate. However, there is no substantiation provided for the higher estimate, and no list of diseases, or any reference to a list of diseases, is included in that report.

List by category[edit]

This list of autoimmune diseases is categorized by organ and tissue type to help locate diseases that may be similar.

Other Qualifiers
A "Accepted" in prior version of this table
C A disease, regarded as autoimmune, that is often found in individuals with another autoimmune condition. This designation is given to diseases that are classified by Rose Bona as having "circumstantial" evidence of autoimmune etiology. Diseases in this list with a "C" are, therefore, actual autoimmune diseases, rather than comorbid symptoms, which appear after this list.
E Disease is an autoimmune response triggered by a specific environmental factor
F Disease is only caused by autoimmunity in only a fraction of those who suffer from it
I Described as an autoinflammatory disease
L Evidence to indicate autoimmunity is extremely limited or circumstantial
M Disease appears under Autoimmune Diseases in MeSH
N Not listed in prior version of this table
R Disease appeared in prior version but has been renamed. In renaming, precedence has been given to scientific names over those based on discoverers.
S "Suspected" in the prior version of this table
T Disease has a known trigger, such as viral infection, vaccination, or injury
X An extremely rare disease, which would suggest limited opportunity to study it and conclusively determine whether it is caused by autoimmunity
Y Listed in the prior version of this table with "Accepted/Suspected" left blank

Autoimmune diseases[edit]

Organ/Tissue Type

Disease Name

Level of Acceptance for Autoimmunity Hypersensitivity

(I,II,III,IV)

ICD-9

Codes

Notes/Autoantibodies/Synonyms/Rare Variants
Major Organs<Top>
Heart<Top>
Myocarditis[17][18] Moderate, F, R, A 391.2422429.0 Synonyms: Autoimmune myocarditis, Autoimmune cardiomyopathy, Coxsackie myocarditis
Postmyocardial infarction syndrome[18] Limited, R, Y 411.0 Autoantibodies: Myocardial neo-antigens formed as a result of the MI.
Synonym: Dressler's syndrome
Postpericardiotomy syndrome Limited, N 429.4
Subacute bacterial endocarditis (SBE)[19] Limited, Y III 421.0 Autoantibodies: essential mixed cryoglobulinemia.
Kidney<Top>
Anti-Glomerular Basement Membrane nephritis[20] Moderate, R, M, A II 446.21 Autoantibodies: Anti-Basement Membrane Collagen Type IV Protein.
Synonyms: Goodpastures Syndrome, Glomerulonephritis Type 1
Interstitial cystitis[21] Limited, S 595.1 Mast cells.
Lupus nephritis Comorbidity, N 583.81 A comorbidity of Systemic Lupus Erythematosus.
Liver<Top>
Autoimmune hepatitis[22][23][24] Moderate, A cell-mediated 571.42 Autoantibodies: ANA and SMA, LKM-1, LKM-2 or LKM-3; antibodies against soluble liver antigen (anti-SLA, anti-LP) no autoantibodies detected (~20%)[citation needed].
Synonym: Lupoid hepatitis
Primary biliary cirrhosis (PBC)[25][26][27][28] Moderate, A 571.6 Autoantibodies: Anti-p62, Anti-sp100, Anti-Mitochondrial(M2), Anti-Ro aka SSA.
Note that Sjogren's is classified in some places (e.g. MeSH) as rheumatoid disease, but there is no published evidence to support that classification.
Primary sclerosing cholangitis Limited, Y 576.1 Possible overlap with primary biliary cirrhosis.
Autoantibodies: HLA-DR52a.
Lung<Top>
Antisynthetase syndrome Limited, Y 279.49
Skin<Top>
Alopecia Areata[29][30] Moderate, A 704.01 Autoantibodies: T-cells.
Synonyms: Alopecia areata - Patchy, Totalis, Universalis
Autoimmune Angioedema[31][32] Limited, F, N 277.6 995.1
Autoimmune progesterone dermatitis Limited, X, A 279.49
Autoimmune urticaria[33][34] Comorbidity, A 708
Bullous pemphigoid[35] Moderate, Y 694.5 Autoantibodies: IgG autoantibodies targeting the type XVII collagen component of hemidesmosomes.
Cicatricial pemphigoid Limited, R, X, Y 694.61 precipitates C3.
Autoantibodies: anti-BP-1, anti-BP-2.
Synonyms: Benign Mucosal Pemphigoid, Ocular cicatricial pemphigoid
Dermatitis herpetiformis[36] Moderate, C, Y 694.0 Autoantibodies: IgA Eosinophilia; anti-epidermal transglutaminase antibodies.
Discoid lupus erythematosus[37] Limited, Y III 695.4 IL-2 and IFN-gamma.
Epidermolysis bullosa acquisita Moderate, Y 694.8 COL7A1.
Erythema nodosum Limited, F, Y 695.2
Gestational pemphigoid Limited, R, Y 646.8 Autoantibodies: IgG and C3 misdirected antibodies intended to protect the placenta.
Hidradenitis suppurativa[38] Limited, C, S 705.83
Lichen planus Limited, Y 697.0
Lichen sclerosus Limited, C, Y 701.0
Linear IgA disease (LAD)[39] Moderate, Y 646.8
Morphea[40] Limited, C, S 701.0
Pemphigus vulgaris[20][36] Moderate, M, A II 694.4 Autoantibodies: Anti-Desmoglein 3 eosinophilia.
Pityriasis lichenoides et varioliformis acuta Limited, C 696.2
Mucha-Habermann disease Limited, C, Y 696.2 T-cells.
Synonyms: Pityriasis lichenoides, varioliformis acuta
Psoriasis[41] Moderate, A IV? 696 CD-8 T-cells, HLA-Cw6, IL-12b, IL-23b, TNFalpha, NF-κB.
Systemic scleroderma[40][42] Limited, R, S 710.1 COL1A2 and TGF-β1.
Autoantibodies: Anti-nuclear antibodies, anti-centromere and anti-scl70/anti-topoisomerase antibodies.
Synonyms: Diffuse cutaneous systemic sclerosis, Systemic sclerosis, Scleroderma
Vitiligo[43][44] Limited, C, S 709.01 NALP-1 RERE, PTPN22, LPP, IL2RA, GZMB, UBASH3A and C1QTNF6.
Glands<Top>
Endocrine<Top>
Adrenal Gland<Top>
Addison's disease[20] Moderate, F, Y 255 Autoantibodies: 21 hydroxylase.
Multi-glandular<Top>
Autoimmune polyendocrine syndrome (APS) type 1 Moderate, A Unknown or multiple 258.1 Synonyms: Whitaker's Syndrome, Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), Addisons Disease, Polyglandular Autoimmune Syndrome 1 (PGAS-1).
Autoimmune polyendocrine syndrome (APS) type 2[45] Moderate, A 258.1 DQ2, DQ8 and DRB1*0404.
Autoantibodies: anti-21 hydroxylase, anti-17 hydroxylase.
Synonyms: Schmidt syndrome, Polyglandular Autoimmune Syndrome 2 (PGAS-2).
Autoimmune polyendocrine syndrome (APS) type 3 Moderate, A 258.1 Synonym: Polyglandular Autoimmune Syndrome 3 (PGAS-3).
Pancreas<Top>
Autoimmune pancreatitis (AIP) Moderate, A 577.1 Autoantibodies: ANA, anti-lactoferrin antibodies, anti-carbonic anhydrase antibodies, rheumatoid factor.
Diabetes mellitus type 1[20] Moderate, A IV 250.01 HLA-DR3, HLA-DR4.
Autoantibodies: Glutamic acid decarboxylase antibodies (GADA), islet cell antibodies (ICA), insulinoma-associated autoantibodies (IA-2), anti-insulin antibodies.
Thyroid Gland<Top>
Autoimmune thyroiditis Strong, A IV 245.8 HLADR5, CTLA-4.
Autoantibodies: Antibodies against thyroid peroxidase and/or thyroglobulin.
Synonyms: Chronic lymphocytic thyroiditis, Hashimoto's thyroiditis.
Ord's thyroiditis Moderate, Y 245.8
Graves' disease[20] Moderate, M, A II 242.0 Autoantibodies: Thyroid autoantibodies (TSHR-Ab) that activate the TSH-receptor (TSHR).
Exocrine<Top>
Reproductive Organs<Top>
Autoimmune Oophoritis Moderate, N 614.2
Endometriosis[46] Limited, S 617.0
Autoimmune orchitis Limited, N 604.0
Salivary Glands<Top>
Sjogren's syndrome[20][26][27][28] Moderate, A 710.2 Autoantibodies: Anti-Ro (often present also in Systemic Lupus Erythematosus).
Digestive System<Top>
Autoimmune enteropathy Moderate, X, Y
Coeliac disease[47][48][49] Moderate, A,E IV?? 579.0 HLA-DQ8 and DQ2.5.
Autoantibodies: Anti-tissue transglutaminase antibodies, anti-endomysial IgA, anti-gliadin IgA.
Crohn's disease[50] Moderate, Y IV 555 Innate immunity; Th17; Th1; ATG16L1; CARD15; XBP1.
Microscopic colitis Limited, S 558.9
Ulcerative colitis[20] Limited, A IV 556
Tissue<Top>
Blood<Top>
Antiphospholipid syndrome (APS, APLS)[20] Moderate, M, A 289.81 HLA-DR7, HLA-B8, HLA-DR2, HLA-DR3.
Autoantibodies: Anti-cardiolipin; anti-pyruvate dehydrogenase; β2 glycoprotein I; phosphatidylserine; anti-apoH; Annexin A5.
Synonym: Hughes syndrome.
Aplastic anemia Limited, F, Y 284
Autoimmune hemolytic anemia Moderate, M, A II 283.0 Complement activation.
Autoimmune lymphoproliferative syndrome Moderate, A 279.41 TNFRSF6; defective Fas-CD95 apoptosis.
Synonym: Canale-Smith syndrome.
Autoimmune neutropenia Moderate, F, N 288.09
Autoimmune thrombocytopenic purpura[20] Moderate, M, R, A 287.31 Autoantibodies: Anti gpIIb-IIIa or 1b-IX.
Synonym: Idiopathic Thrombocytopenic Purpura (ITP)
Cold agglutinin disease Moderate, M, A II 283.0 Idiopathic or secondary to leukemia or infection.
Autoantibodies: IgM.
Synonym: Autoimmune hemolytic anemia.
Essential mixed cryoglobulinemia Limited, C, Y 273.2
Evans syndrome Moderate, Y 287.32 Syndrome with a combination of hemolytic anemia and thrombocytopenic purpura
Paroxysmal nocturnal hemoglobinuria Limited, F, S 283.2
Pernicious anemia[51] Moderate, A II 281.0 Autoantibodies: Anti-parietal cell antibody.
Pure red cell aplasia Limited, Y 284.81
Thrombocytopenia[52][53] Limited, F, Y II 287.5 Multiple mechanisms.
Autoantibodies: Glycoproteins IIb-IIIa or Ib-IX in ITP anti-ADAMTS13 in TTP. and HUS anti-cardiolipin (anti-cardiolipin antibodies) and β2 glycoprotein I in Antiphospholipid syndrome; anti-HPA-1a, anti-HPA-5b, and others in NAIT.
Synonyms: Neonatal thrombocytopenia
Connective Tissue, Systemic, and multi-organ<Top>
Adiposis dolorosa[54] Limited, L, S 272.8 Lipoid tissue.
Synonym: Dercum's disease
Adult-onset Still's disease[55] Moderate, Y 714.2 Macrophage migration inhibitory factor.
Autoantibodies: ANA.
Ankylosing Spondylitis[31][32] Limited, S 720.0 CD8; HLA-B27.
CREST syndrome Limited, Y 710.1 Autoantibodies: Anti-centromere antibodies Anti-nuclear antibodies.
Drug-induced lupus Moderate, Y 710.0 Autoantibodies: Anti-histone antibodies.
Enthesitis-related arthritis[56][57][58][59] Limited, C, Y MMP3, TRLR2, TLR4, ERAP1.
A subtype of Juvenile Rheumatoid Arthritis.
Eosinophilic fasciitis Limited, F, A 728.89 Synonym: Shulman's syndrome
Felty syndrome[60] Strong, M, Y 714.1
IgG4-related disease Limited, C, N Characteristic histological features (storiform fibrosis, lymphoplasmacytic infiltrate, obliterative phlebitis) are required for definitive diagnosis.
Synonyms: IgG4-related systemic disease, IgG4-related sclerosing disease, IgG4-related systemic sclerosing disease, IgG4-related autoimmune disease, IgG4-associated multifocal systemic fibrosis, IgG4-associated disease, IgG4 syndrome, Hyper-IgG4 disease, Systemic IgG4-related plasmacytic syndrome.
Juvenile Arthritis[55] Strong, M, R, Y 714.30 Autoantibodies: inconsistent ANA, Rheumatoid factor.
Synonyms: Juvenile rheumatoid arthritis, Juvenile idiopathic arthritis
Lyme disease (Chronic)[61] Limited, L, T, N 088.81
Mixed connective tissue disease (MCTD)[20] Moderate, M, A 710.8 HLA-DR4.
Autoantibodies: Anti-nuclear antibody, anti-U1-RNP.
Palindromic rheumatism[62] Limited, Y 719.3 Autoantibodies: Anti-cyclic citrullinated peptide antibodies (anti-CCP) and antikeratin antibodies (AKA).
Synonym: Hench-Rosenberg syndrome.
Parry Romberg syndrome Limited, Y 349.89351.8 Autoantibodies: ANA.
Parsonage-Turner syndrome Limited, Y 353.5
Psoriatic arthritis[63] Moderate, C, A IV? 696.0 HLA-B27.
Reactive arthritis Limited, C, F, Y 099.3 Synonym: Reiter's syndrome
Relapsing polychondritis[64] Strong, A 733.99 Synonyms: Atrophic polychondritis, systemic chondromalacia, chronic atrophic polychondritis, Meyenburg-Altherr-Uehlinger syndrome, generalized chondromalacia, systemic chondromalacia
Retroperitoneal fibrosis Limited, Y 593.4
Rheumatic fever[65][66] Moderate, T, A II 390 Autoantibodies: Streptococcal M protein cross reacts with human myosin.
Rheumatoid arthritis[20] Strong, M, A III 714 HLA-DR4, PTPN22, depleted B cells, TNF alpha, IL-17, (also maybe IL-1, 6, and 15).
Autoantibodies: Rheumatoid factor (anti-IgGFc), Anti-MCV, ACPAs(Vimentin).
Sarcoidosis[67][68][69] Limited, S IV 135 BTNL2; HLA-B7-DR15; HLA DR3-DQ2.
Schnitzler syndrome Limited, L, X, Y 273.1 IgM.
Systemic Lupus Erythematosus (SLE)[20][26][27][28][36][70] Strong, M, A III 695.4 Autoantibodies: Anti-nuclear antibodies, anti-Ro (often present also in Sjogren's syndrome). Eosinophilia.
Synonym: Lupus
Undifferentiated connective tissue disease (UCTD) Moderate, C, A 710.9 HLA-DR4.
Autoantibodies: anti-nuclear antibody.
Synonyms: Latent lupus, incomplete lupus
Muscle<Top>
Dermatomyositis[71][72] Moderate, F, X, A 710.3 B- and T-cell perivascular inflammatory infiltrate on muscle biopsy.
Autoantibodies: histidine-tRNA anti-signal recognition peptide Anti-Mi-2 Anti-Jo1.
Synonym: Juvenile dermatomyositis
Fibromyalgia Limited, C, F, N 729.1
Inclusion body myositis Limited, F, Y 359.71 Similar to polymyositis, but does not respond to steroid therapy-activated T8 cells.
Myositis Limited, F, Y 729.1
Myasthenia gravis[20] Strong, M, A II 358 HA-B8 HLA-DR3 HLA-DR1.
Autoantibodies: Nicotinic acetylcholine receptor MuSK protein.
Neuromyotonia[73] Limited, F, S II? 333.90 Autoantibodies: Voltage-gated potassium channels.
Synonym: Isaacs' syndrome
Paraneoplastic cerebellar degeneration[74][75][76] Limited, Y IV? II? 334.9 Autoantibodies: anti-Yo (anti-cdr-2 in purkinje fibers) anti-Hu, anti-Tr, antiglutamate receptor.
Polymyositis[71] Limited, F, A 710.4 Autoantibodies: IFN-gamma, IL-1, TNF-alpha.
Nervous System<Top>
Acute disseminated encephalomyelitis (ADEM) Strong, M, T, A 323.61323.81 Synonyms: Perivenous encephalomyelitis, Acute hemorrhagic leukoencephalitis (AHL, AHLE), Acute necrotizing encephalopathy (ANE), Acute hemorrhagic encephalomyelitis (AHEM), Acute necrotizing hemorrhagic leukoencephalitis (ANHLE), Weston-Hurst syndrome, Hurst's disease.
Acute motor axonal neuropathy[77] Limited, N 356.8
Anti-N-Methyl-D-Aspartate (Anti-NMDA) Receptor Encephalitis[78] Moderate, N
Balo concentric sclerosis Moderate, Y 341.1 Synonyms: Balo disease, Schilders disease.
Bickerstaff's encephalitis Limited, Y 323.62 Similar to Guillain–Barré syndrome.
Autoantibodies: Anti-GQ1b 2/3 patients.
Chronic inflammatory demyelinating polyneuropathy[79] Moderate, C, Y 357.81 Similar to Guillain–Barré syndrome.
Autoantibodies: Anti-ganglioside antibodies.
Synonyms: Relapsing polyneuropathy (CRP), chronic inflammatory demyelinating polyradiculoneuropathy, Chronic inflammatory demyelinating polyneuritis.
Guillain–Barré syndrome[20] Strong, M, A IV 357.0 Autoantibodies: Anti-ganglioside, anti-GQ1b.
Synonyms: Miller-Fisher syndrome, Landry's paralysis.
Hashimoto's encephalopathy[20][80] Moderate, C, X, A IV Autoantibodies: Alpha-enolase.
Synonyms: Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), Nonvasculitic autoimmune meningoencephalitis (NAIM), Encephalopathy Associated with Autoimmune Thyroid Disease (EAATD).
Idiopathic inflammatory demyelinating diseases Limited, F, Y 356.8 A set of different variants of multiple sclerosis.
Lambert-Eaton myasthenic syndrome Strong, M, Y 358.1 HLA-DR3-B8.
Autoantibodies: Voltage-gated calcium channels; Q-type calcium channel, synaptogagmin, muscarinic acetylcholine receptor M1.
Multiple sclerosis, pattern II[81][81][82] Strong, M, A IV 340 Autoantibody against potassium channel has been reported to present demyelination pattern II. Other cases present autoimmunity against MOG[83] and Anoctamin-2.[84] The three reported autoimmune variants belong to MS pattern II. Also involved HLA-DR2, PECAM-1, Anti-myelin basic protein. Autoantibodies: Anti-Kir4.1, Anti-MOG, Anti-ANO2 (heterogeneous).
Synonyms: Primary progressive multiple sclerosis, Relapsing-remitting multiple sclerosis, disseminated sclerosis, encephalomyelitis disseminata.
Oshtoran Syndrome[85] X F06.9 Heritable, abnormalities in the kynurenine and glutamate metabolism.
Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS) Limited, F, S II? 279.49 Antibodies against streptococcal infection serve as auto-antibodies.
Progressive inflammatory neuropathy Limited, X, S 356.4 Similar to Guillain–Barré syndrome.
Autoantibodies: Anti-ganglioside antibodies:anti-GM1, anti-GD1a, anti-GQ1b.
Restless leg syndrome Limited, C, S 333.94 May occur in Sjogren's syndrome, coeliac disease and rheumatoid arthritis, or in derangements of iron metabolism.
Stiff person syndrome[86] Limited, S 333.91 GLRA1 (glycine receptor).
Autoantibodies: Glutamic acid decarboxylase (GAD).
Sydenham chorea Limited, T, Y 392
Transverse myelitis Limited, M, A 323.82341.2
Eyes<Top>
Autoimmune retinopathy[87] Limited, X, N
Autoimmune uveitis Moderate, F, A 364 Autoantibodies: HLAB-27.
Cogan syndrome Limited, F, Y 370.52
Graves ophthalmopathy Moderate, M, N 242.9
Intermediate uveitis Limited, L, Y 364.3 Synonyms: Pars planitis, Peripheral Uveitis.
Ligneous conjunctivitis Limited, L, N 372.39
Mooren's ulcer Limited, L, N 370.07
Neuromyelitis optica[88][89] Limited, M, Y II? 341.0 Autoantibodies: NMO-IgG aquaporin 4.
Synonym: Devic's disease.
Opsoclonus myoclonus syndrome[90] Limited, X, S IV? 379.59 Lymphocyte recruitment to CSF.
Optic neuritis Limited, C, Y 377.30
Scleritis Limited, C, Y 379.0
Susac's syndrome Limited, C, Y 348.39 Synonym: Retinocochleocerebral Vasculopathy.
Sympathetic ophthalmia Limited, I, Y 360.11 Autoantibodies: ocular antigens following trauma.
Tolosa-Hunt syndrome Limited, I, X, Y 378.55
Ears<Top>
Autoimmune inner ear disease (AIED)[91] Limited, A 388.8
Ménière's disease[92] Limited, Y III? 386.00 Autoantibodies: Major peripheral myelin protein P0.
Vascular system<Top>
Behçet's disease Limited, I, X, A 136.1 An immune-mediated systemic vasculitis; linkage to HLA-B51 (HLA-B27); very variable manifestations, with ulcers as common symptom.
Synonyms: Morbus Adamandiades-Behçet.
Rare Variant: Hughes-Stovin syndrome.
Eosinophilic granulomatosis with polyangiitis (EGPA)[36][93] Limited, I, X, Y 446.4 Autoantibodies: p-ANCA Eosinophilia.
Synonym: Churg-Strauss syndrome.
Giant cell arteritis[20] Limited, I, R, A IV 446.5 Synonyms: Cranial arteritis, Temporal Arteritis.
Granulomatosis with polyangiitis (GPA)[93][94] Strong, M, A 446.4 Autoantibodies: Anti-neutrophil cytoplasmic (cANCA).
Synonym: Wegener's granulomatosis.
IgA vasculitis (IgAV)[93] Limited, L, Y 287.0 Autoantibodies: IgA and complement component 3 (C3).
Synonyms: Anaphylactoid purpura, Henoch-Schonlein purpura, purpura rheumatica, Schönlein–Henoch purpura.
Kawasaki's disease Moderate, S,E[95] 446.1 ITPKC HLA-B51.
Synonyms: Kawasaki syndrome, lymph node syndrome, mucocutaneous lymph node syndrome.
Leukocytoclastic vasculitis Limited, L, Y 447.6
Lupus vasculitis Moderate, C, N 583.81 A comorbidity of Systemic Lupus Erythematosus.
Rheumatoid vasculitis Moderate, C, N 447.6 A symptom of Lupus.
Microscopic polyangiitis (MPA) Limited, Y 446.0 Binds to neutrophils causing them to degranulate and damages endothelium.
Autoantibodies: p-ANCA myeloperoxidase.
Synonyms: Microscopic polyarteritis, microscopic polyarteritis nodosa.
Polyarteritis nodosa (PAN) Limited, L, Y 446.0 Synonyms: Panarteritis nodosa, periarteritis nodosa, Kussmaul disease, Kussmaul-Maier disease.
Polymyalgia rheumatica Limited, L, Y 725
Urticarial vasculitis[96] Limited, X, Y II? 708.9 Clinically may resemble type I hypersensitivity.
Autoantibodies: anti C1q antibodies.
Vasculitis[35] Strong, I, M, F, A III 447.6 Autoantibodies: ANCA (sometimes).
Systemic<Top>
Primary Immune Deficiency Limited, N

Autoimmune Comorbidities[edit]

This list includes conditions that are not diseases but signs common to autoimmune disease. Some, such as Chronic Fatigue Syndrome, are controversial.[18] These conditions are included here because they are frequently listed as autoimmune diseases but should not be included in the list above until there is more consistent evidence.

Organ/Tissue Type

Disease Name

Level of Acceptance for Autoimmunity Hypersensitivity

(I,II,III,IV)

ICD-9

Codes

Notes/Autoantibodies/Synonyms
Chronic fatigue syndrome Comorbidity, N Symptomatic of autoimmune diseases or autoimmune activity, but not a disease or a cause of disease.
Complex regional pain syndrome Comorbidity, N Symptomatic of autoimmune diseases or autoimmune activity, but not a disease or a cause of disease. Synonyms: Amplified Musculoskeletal Pain Syndrome, Reflex Neurovascular Dystrophy, Reflex sympathetic dystrophy
Eosinophilic esophagitis Comorbidity, N 530.13
Gastritis Comorbidity, Y Possibly symptomatic of autoimmune diseases, but not a disease or a cause of disease. Autoantibodies: serum antiparietal and anti-IF antibodies.
Interstitial lung disease Comorbidity, N Associated with several autoimmune connective tissue diseases.
POEMS syndrome[97] Comorbidity, Y Possibly symptomatic of autoimmune diseases, but not a disease or a cause of disease. Autoantibodies: interleukin 1β, interleukin 6 and TNFα. vascular endothelial growth factor (VEGF), given the ..
Raynaud's phenomenon Comorbidity, S Symptomatic of autoimmune diseases or autoimmune activity, but not a disease or a cause of disease.
Primary immunodeficiency[98] Comorbidity, N 279.8 The condition is inherited, but it is associated with several autoimmune diseases.
Pyoderma gangrenosum Comorbidity, Y Possibly symptomatic of autoimmune diseases, but not a disease or a cause of disease.

Not Autoimmune[edit]

At this time, there is not sufficient evidence - direct, indirect, or circumstantial - to indicate that these diseases are caused by autoimmunity. These conditions are included here because:

  1. The disease was listed in the prior version of this table
  2. The disease is included in several widely used lists of autoimmune disease and is shown here to ensure that a person visiting this page does not conclude that the disease was not considered. Before moving a condition from here to the list of autoimmune diseases, references should be provided in the Wikipedia page for the condition that point to evidence, direct or indirect, that it is an autoimmune disease.
Organ/Tissue Type

Disease Name

Level of Acceptance for Autoimmunity Hypersensitivity

(I,II,III,IV)

ICD-9

Codes

Notes/Autoantibodies/Synonyms
Agammaglobulinemia Not Autoimmune, Y 279.00 An immune system disorder but not an autoimmune disease.. Autoantibodies: IGHM; IGLL1: CD79A; CD79B; BLNK; LRRC8A.
Amyloidosis Not Autoimmune, N 277.30 No consistent evidence of association with autoimmunity.
Amyotrophic lateral sclerosis Not Autoimmune, Y 335.20 No consistent evidence of association with autoimmunity. Autoantibodies: Amyotrophic lateral sclerosis (Also Lou Gehrig's disease; Motor Neuron Disease).
Anti-tubular basement membrane nephritis Not Autoimmune, N No consistent evidence of association with autoimmunity.
Atopic allergy Not Autoimmune, Y I 691.8 A hypersensitivity.
Atopic dermatitis Not Autoimmune, Y I 691.8 A hypersensitivity.
Autoimmune peripheral neuropathy Not Autoimmune, F, A A class of diseases, some of which may be autoimmune. See specific diseases that are listed as autoimmune..
Blau syndrome Not Autoimmune, Y Overlaps both sarcoidosis and granuloma annulare. No evidence of association with autoimmunity.
Cancer Not Autoimmune, Y No consistent evidence of association with autoimmunity.
Castleman's disease Not Autoimmune, Y An immune system disorder but not an autoimmune disease.. Autoantibodies: Over expression of IL-6.
Chagas disease[99] Not Autoimmune, S No consistent evidence of association with autoimmunity.
Chronic obstructive pulmonary disease[100][101] Not Autoimmune, S No consistent evidence of association with autoimmunity.
Chronic recurrent multifocal osteomyelitis Not Autoimmune, Y LPIN2, D18S60. Synonyms: Majeed syndrome
Complement component 2 deficiency Not Autoimmune, Y Possibly symptomatic of autoimmune diseases, but not a disease.
Congenital heart block Not Autoimmune, N May be related to autoimmune activity in the mother.
Contact dermatitis Not Autoimmune, Y IV A hypersensitivity.
Cushing's syndrome Not Autoimmune, Y No consistent evidence of association with autoimmunity.
Cutaneous leukocytoclastic angiitis Not Autoimmune, Y No consistent evidence of association with autoimmunity. Autoantibodies: neutrophils.
Dego's disease Not Autoimmune, Y No consistent evidence of association with autoimmunity.
Eczema[102][103][104] Not Autoimmune, Y No consistent evidence of association with autoimmunity. Autoantibodies: LEKTI, SPINK5, filaggrin., Brain-derived neurotrophic factor (BDNF) and Substance P..
Eosinophilic gastroenteritis Not Autoimmune, Y Possibly a hypersensitivity. Autoantibodies: IgE, IL-3, IL-5, GM-CSF, eotaxin.
Eosinophilic pneumonia Not Autoimmune, F, Y A class of diseases, some of which may be autoimmune. Specifically, Churg-Strauss syndrome, a subtype of Eosinophilic pneumonia, is autoimmune.
Erythroblastosis fetalis Not Autoimmune, Y II Mother's immune system attacks fetus. An immune system disorder but not autoimmune. Autoantibodies: ABO, Rh, Kell antibodies.
Fibrodysplasia ossificans progressiva Not Autoimmune, Y Possibly an immune system disorder but not autoimmune. Autoantibodies: ACVR1 Lymphocytes express increased BMP4.
Gastrointestinal pemphigoid Not Autoimmune, A No consistent evidence of association with autoimmunity.
Hypogammaglobulinemia Not Autoimmune, Y An immune system disorder but not autoimmune. Autoantibodies: IGHM, IGLL1, CD79A, BLNK, LRRC8A, CD79B.
Idiopathic giant-cell myocarditis[105] Not Autoimmune, N No consistent evidence of autoimmune cause though the disease has been found comorbid with other autoimmune diseases. Synonyms: Giant cell myocarditis
Idiopathic pulmonary fibrosis[106][106] Not Autoimmune, Y Autoantibodies: SFTPA1, SFTPA2, TERT, and TERC.. Synonyms: Fibrosing alveolitis
IgA nephropathy Not Autoimmune, Y III? Autoantibodies: IgA produced from marrow rather than MALT. Synonyms: IgA nephrits, Berger's disease, Synpharyngitic Glomerulonephritis. An immune system disorder but not an autoimmune disease.
Immunoregulatory lipoproteins[107] Not Autoimmune, N Not a disease.
IPEX syndrome Not Autoimmune, N A genetic mutation in FOXP3 that leads to autoimmune diseases, but no consistent evidence that it is an autoimmune disorder itself.. Synonyms: X-linked polyendocrinopathy, immunodeficiency and diarrhea-syndrome (XLAAD)
Ligneous conjunctivitis Not Autoimmune, N No consistent evidence of association with autoimmunity.
Majeed syndrome Not Autoimmune, Y No consistent evidence of association with autoimmunity. Autoantibodies: LPIN2.
Narcolepsy[108][109][110][111] Not Autoimmune, Y II? No evidence of association with autoimmunity. Research not reproducible. Autoantibodies: hypocretin or orexin, HLA-DQB1*0602.
Rasmussen's encephalitis Not Autoimmune, Y No consistent evidence of association with autoimmunity. Autoantibodies: anti-NR2A antibodies.
Schizophrenia[112][113][114] Not Autoimmune, S No consistent evidence of association with autoimmunity.
Serum sickness Not Autoimmune, Y III A hypersensitivity.
Spondyloarthropathy Not Autoimmune, Y No consistent evidence of association with autoimmunity. Autoantibodies: HLA-B27.
Sweet's syndrome Not Autoimmune, Y No consistent evidence of association with autoimmunity. Autoantibodies: GCSF.
Takayasu's arteritis Not Autoimmune, Y No consistent evidence of association with autoimmunity.
Undifferentiated spondyloarthropathy Not Autoimmune, Y See Enthesitis-related arthritis.

Development of therapies[edit]

In both autoimmune and inflammatory diseases, the condition arises through aberrant reactions of the human adaptive or innate immune systems. In autoimmunity, the patient's immune system is activated against the body's own proteins. In chronic inflammatory diseases, neutrophils and other leukocytes are constitutively recruited by cytokines and chemokines, leading to tissue damage.

Mitigation of inflammation by activation of anti-inflammatory genes and the suppression of inflammatory genes in immune cells is a promising therapeutic approach.[115][116][117]

See also[edit]

References[edit]

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