Autoimmune disease

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Autoimmune diseases
Classification and external resources
ICD-10D84.9, M35.9
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Autoimmune diseases
Classification and external resources
ICD-10D84.9, M35.9

Autoimmune diseases arise from an abnormal immune response of the body against substances and tissues normally present in the body (autoimmunity). 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.

A large number 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.[1]


For a disease to be regarded as an autoimmune disease it needs to answer to Witebsky's postulates (first formulated by Ernst Witebsky and colleagues in 1957 and modified in 1994):[2][3]


It has been estimated that autoimmune diseases are among the top ten leading causes of death among women in all age groups up to 65 years.[4]

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

There are more than 80 illnesses caused by autoimmunity.[5]


It is possible to classify autoimmune diseases by corresponding type of hypersensitivity: type II, type III, or type IV. (No type of autoimmune disease mimics type I hypersensitivity.)[6]

There is continuing debate about when a disease should be considered autoimmune, leading to different criteria such as Witebsky's postulates.



Acute disseminated encephalomyelitis (ADEM)Accepted[7]
Addison's disease21 hydroxylase
AgammaglobulinemiaIGHM; IGLL1: CD79A; CD79B; BLNK; LRRC8A
Alopecia areataAccepted[8][9]T-cells
Amyotrophic lateral sclerosis (Also Lou Gehrig's disease; Motor Neuron Disease)VCP, ATXN2, OPTN, FIG4, TARDBP, ANG, VAPB, FUS, SETX, ALS2, SOD1
Ankylosing SpondylitisSuspected[10][11]CD8; HLA-B27
Antiphospholipid syndromeAccepted[7]anti-cardiolipin;anti pyruvate dehydrogenase; β2 glycoprotein I; phosphatidylserine; anti apoH; Annexin A5HLA-DR7, HLA-B8, HLA-DR2, HLA-DR3
Antisynthetase syndrome
Atopic allergyI
Atopic dermatitisI
Autoimmune aplastic anemia
Autoimmune cardiomyopathyAccepted
Autoimmune enteropathy
Autoimmune hemolytic anemiaAcceptedIIcomplement activation
Autoimmune hepatitisAcceptedcell-mediatedanti-mitochondrial antibodies; ANA; anti-smooth muscle antibodies, LKM-1; soluble liver antigen
Autoimmune inner ear diseaseAccepted[12]
Autoimmune lymphoproliferative syndromeAcceptedTNFRSF6; defective Fas-CD95 apoptosis
Autoimmune peripheral neuropathyAccepted
Autoimmune pancreatitisAcceptedANA; anti-lactoferrin antibodiesanti-carbonic anhydrase antibodies; rheumatoid factor
Autoimmune polyendocrine syndromeAcceptedUnknown or multipleAPS-1 see Addison's disease
Autoimmune progesterone dermatitisAccepted
Autoimmune thrombocytopenic purpuraAcceptedanti gpIIb-IIIa or 1b-IX
Autoimmune urticariaAccepted[13]
Autoimmune uveitisAcceptedHLAB-27?
Balo disease/Balo concentric sclerosis
Behçet's diseaseAcceptedimmune-mediated systemic vasculitis; linkage to HLA-B51 (HLA-B27); very different manifestations with ulcers as common symptom; also called Morbus Adamandiades-Behçet
Berger's diseaseIgA (elevated in 50% of patients), IgA (in mesangial deposits on kidney biopsy)
Bickerstaff's encephalitisAnti-GQ1b 2/3 patientssimilar to Guillain-Barré syndrome
Blau syndromeoverlaps both sarcoidosis and granuloma annulare
Bullous pemphigoidIgG autoantibodies targeting the type XVII collagen component of hemidesmosomes[14]
Castleman's diseaseOver expression of IL-6
Celiac diseaseAccepted[15][16][17]IV??Anti-tissue transglutaminase antibodies anti-endomysial IgA, anti-gliadin IgAHLA-DQ8 and DQ2.5
Chagas diseaseSuspected[18]
Chronic inflammatory demyelinating polyneuropathyAnti-ganglioside antibodies:anti-GM1, anti-GD1a, anti-GQ1bsimilar to Guillain-Barré syndrome
Chronic recurrent multifocal osteomyelitisLPIN2, D18S60,similar to Majeed syndrome
Chronic obstructive pulmonary diseaseSuspected[19][20]
Churg-Strauss syndromep-ANCA Eosinophilia[21]
Cicatricial pemphigoidanti-BP-1, anti BP-2precipitates C3
Cogan syndrome
Cold agglutinin diseaseAcceptedIIIgMidiopathic or secondary to leukemia or infection
Complement component 2 deficiency
Contact dermatitisIV
Cranial arteritisaka Temporal arteritis; involves giant cells
CREST syndromeAnti-centromere antibodies Anti-nuclear antibodies
Crohn's diseaseImmune related[22]IVInnate immunity; Th17; Th1; ATG16L1; CARD15;XBP1;
Cushing's Syndromecortisol binding globulin?
Cutaneous leukocytoclastic angiitisneutrophils
Dego's diseaseVasculopathy
Dercum's diseaseSuspectedLipoid tissue.[23]
Dermatitis herpetiformisIgA Eosinophilia;[21] anti-epidermal transglutaminase antibodies
DermatomyositisAccepted[24]histidine-tRNA anti-signal recognition peptide Anti-Mi-2 Anti-Jo1.[25]B- and T-cell perivascular inflammatory infiltrate on muscle biopsy
Diabetes mellitus type 1Accepted[7]IVGlutamic acid decarboxylase antibodies (GADA), islet cell antibodies (ICA), and insulinoma-associated autoantibodies (IA-2), anti-insulin antibodiesHLA-DR3, HLA-DR4
Diffuse cutaneous systemic sclerosisanti-nuclear antibodies, anti-centromere and anti-scl70/anti-topoisomerase antibodies[26]COL1A2 and TGF-β1
Dressler's syndromemyocardial neo-antigens formed as a result of the MI
Drug-induced lupusAnti-histone antibodies
Discoid lupus erythematosusIIIIL-2 and IFN-gamma>[27]
EczemaLEKTI, SPINK5,[28] filaggrin.,[29] Brain-derived neurotrophic factor (BDNF) and Substance P.[30]
Enthesitis-related arthritis[32].MMP3[33] TRLR2, TLR4,[34] ERAP1[35]
Eosinophilic fasciitisAccepted
Eosinophilic gastroenteritisIgEIL-3, IL-5, GM-CSF, eotaxin
Eosinophilic pneumonia
Epidermolysis bullosa acquisitaCOL7A1
Erythema nodosum
Erythroblastosis fetalisIIABO, Rh, Kell antibodiesmother's immune system attacks fetus
Essential mixed cryoglobulinemia
Evan's syndrome
Fibrodysplasia ossificans progressivaACVR1 Lymphocytes express increased BMP4
Fibrosing alveolitis (or Idiopathic pulmonary fibrosis)SFTPA1, SFTPA2, TERT, and TERC.[36]
Gastritisserum antiparietal and anti-IF antibodies
Gastrointestinal pemphigoidAccepted
GlomerulonephritisSometimesIgAsee Buerger's disease for IgA; Membranous glomerulonephritis for IgG; Membranoproliferative/mesangiocapillary GN (Complement activation); Goodpasture's syndrome; Wegener's granulomatosis
Goodpasture's syndromeAccepted[7]IIAnti-Basement Membrane Collagen Type IV Protein
Graves' diseaseAccepted[7]IIthyroid autoantibodies (TSHR-Ab) that activate the TSH-receptor (TSHR)
Guillain-Barré syndrome (GBS)Accepted[7]IVAnti-ganglioside
Hashimoto's encephalopathyAccepted[7]IValpha-enolase[37]
Hashimoto's thyroiditisAccepted[7]IVantibodies against thyroid peroxidase and/or thyroglobulinHLADR5, CTLA-4
Henoch-Schonlein purpuraimmunoglobulin A (IgA) and complement component 3 (C3)
Herpes gestationis aka Gestational PemphigoidIgG and C3 misdirected antibodies intended to protect the placenta
Hidradenitis suppurativaSuspected[38]
Hughes-Stovin syndrome
HypogammaglobulinemiaIGHM, IGLL1, CD79A, BLNK, LRRC8A, CD79B
Idiopathic inflammatory demyelinating diseasesa variant of multiple sclerosis
Idiopathic pulmonary fibrosisSFTPA1, SFTPA2, TERT, and TERC.[36]
Idiopathic thrombocytopenic purpura (See Autoimmune thrombocytopenic purpura)Accepted[7]IIglycoproteins IIb-IIIa or Ib-IX, immunoglobulin G
IgA nephropathyIII?IgA produced from marrow rather than MALT
Inclusion body myositissimilar to polymyositis but does not respond to steroid therapy-activated T8 cells
Chronic inflammatory demyelinating polyneuropathyanti-ganglioside antibodiessimilar to Guillain–Barré syndrome
Interstitial cystitisSuspected[39]Mast cells
Juvenile idiopathic arthritis aka Juvenile rheumatoid arthritisinconsistent ANA Rheumatoid factor
Kawasaki's diseaseSuspectedITPKC HLA-B51
Lambert-Eaton myasthenic syndromevoltage-gated calcium channels; Q-type calcium channel, synaptogagmin, muscarinic acetylcholine receptor M1HLA-DR3-B8
Leukocytoclastic vasculitis
Lichen planus
Lichen sclerosus
Linear IgA disease (LAD)
Lupoid hepatitis aka Autoimmune hepatitisANA and SMA,[40] LKM-1, LKM-2 or LKM-3; antibodies against soluble liver antigen[41][42] (anti-SLA, anti-LP) no autoantibodies detected (~20%)[citation needed]
Lupus erythematosusAccepted[7]IIIAnti-nuclear antibodies[43] anti-Ro.[44] Also, they are often present in Sjögren's syndrome.[45][46]Eosinophilia[21]
Majeed syndromeLPIN2
Ménière's diseaseIII?major peripheral myelin protein P0[47]
Microscopic polyangiitisp-ANCA myeloperoxidasebinds to neutrophils causing them to degranulate and damages endothelium
Miller-Fisher syndrome see Guillain-Barre SyndromeAcceptedanti-GQ1b
Mixed connective tissue diseaseAccepted[7]anti-nuclear antibody anti-U1-RNPHLA-DR4
Mucha-Habermann disease aka Pityriasis lichenoides et varioliformis acutaT-cells
Multiple sclerosisAccepted[49]IVAnti-Kir4.1 (heterogeneous)[49]Autoantibody against potassium channel. Also invoved HLA-DR2, PECAM-1[50] Anti-myelin basic protein
Myasthenia gravisAccepted[7]IInicotinic acetylcholine receptor MuSK proteinHA-B8 HLA-DR3 HLA-DR1
Microscopic colitisSuspected
Myositissee Dermatomyositis and Polymyositis see Inclusion-body-myositis
Narcolepsy[51][52]AcceptedII?hypocretin or orexin[53]HLA-DQB1*0602[54]
Neuromyelitis optica (also Devic's disease)II?NMO-IgG aquaporin 4.[55][56]
NeuromyotoniaSuspected[57]II?voltage-gated potassium channels.[57]
Occular cicatricial pemphigoidII?BP-1, BP-2C3 deposition
Opsoclonus myoclonus syndromeSuspectedIV?Lymphocyte recruitment to CSF[58]
Ord's thyroiditis
Palindromic rheumatismanti-cyclic citrullinated peptide antibodies (anti-CCP) and antikeratin antibodies (AKA)[59]
PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcus)SuspectedII?antibodies against streptococcal infection serve as auto-antibodies
Paraneoplastic cerebellar degenerationIV?[60] II?anti-Yo[61] (anti-cdr-2[62] in purkinje fibers) anti-Hu, anti-Tr, antiglutamate receptor
Paroxysmal nocturnal hemoglobinuria (PNH)Sometimes(?)complement attacks RBCs
Parry Romberg syndromeANA
Parsonage-Turner syndrome
Pars planitis
Pemphigus vulgarisAccepted[7]IIAnti-Desmoglein 3 eosinophilia[21]
Pernicious anaemiaAccepted[63]IIanti-parietal cell antibody
Perivenous encephalomyelitis
POEMS syndromeinterleukin 1β, interleukin 6 and TNFα. vascular endothelial growth factor (VEGF), given the .[64]
Polyarteritis nodosa
Polymyalgia rheumatica
PolymyositisAccepted[24]IFN-gamma, IL-1, TNF-alpha
Primary biliary cirrhosisAccepted[65]Anti-p62, Anti-sp100, Anti-Mitochondrial(M2)Anti-Ro aka SSA.[44] Also, they are often present in Sjögren's syndrome.[45][46]
Primary sclerosing cholangitisHLA-DR52aoverlap with primary biliary cirrhosis?
Progressive inflammatory neuropathySuspected
PsoriasisAccepted[66]IV?CD-8 T-cells, HLA-Cw6, IL-12b, IL-23b, TNFalpha, NF-κB
Psoriatic arthritisAccepted[67]IV?HLA-B27
Pyoderma gangrenosumCan occur in conjunction with other immune-related disorders
Pure red cell aplasia
Rasmussen's encephalitisanti-NR2A antibodies
Raynaud phenomenonSuspectedCan occur in conjunction with other immune-related disorders
Relapsing polychondritisAccepted[68]
Reiter's syndrome
Restless leg syndromeSuspectedMay occur in Sjögren's syndrome, celiac disease, and rheumatoid arthritis or in derangements of iron metabolism
Retroperitoneal fibrosis
Rheumatoid arthritisAccepted[7]IIIRheumatoid factor (anti-IgGFc), Anti-MCV, ACPAs(VimentinHLA-DR4, PTPN22, depleted B cells, TNF alpha, IL-17, (also maybe IL-1, 6, and 15)
Rheumatic feverAccepted[69]IIstreptococcal M protein cross reacts with human myosin,[70]
SarcoidosisSuspectedIV[71][72]BTNL2; HLA-B7-DR15; HLA DR3-DQ2.[73]
Schmidt syndrome another form of APSanti-21 hydroxylase, anti-17 hydroxylase[77]DQ2, DQ8 and DRB1*0404
Schnitzler syndromeIgM?
SclerodermaSuspected[48]IV?Scl-70 Anti-topoisomerasedysregulated apoptosis?
Serum SicknessIII
Sjögren's syndromeAccepted[7]anti-Ro.[44] Also, they are often present in Sjögren's syndrome.[45][46]
Still's disease see Juvenile Rheumatoid ArthritisANAmacrophage migration inhibitory factor[78]
Stiff person syndromeSuspectedglutamic acid decarboxylase (GAD),[79]GLRA1 (glycine receptor)
Subacute bacterial endocarditis (SBE)III [80]essential mixed cryoglobulinemia
Susac's syndrome
Sweet's syndromeGCSF
Sydenham chorea see PANDAS
Sympathetic ophthalmiaocular antigens following trauma
Systemic lupus erythematosus see Lupus erythematosusIII
Takayasu's arteritis
Temporal arteritis (also known as "giant cell arteritis")Accepted[7]IV
ThrombocytopeniaIIglycoproteins IIb-IIIa or Ib-IX in ITP anti-ADAMTS13 in TTP.[81] and HUS anti-cardiolipin (anti-cardiolipin antibodies) and β2 glycoprotein I in Antiphospholipid syndrome anti-HPA-1a, anti-HPA-5b, and others[82] in NAITmultiple mechanisms
Tolosa-Hunt syndrome
Transverse myelitisAcceptedTransverse Myelitis is a rare neurological disorder that is part of a spectrum of neuroimmunologic diseases of the central nervous system.
Ulcerative colitis (one of two types of idiopathic inflammatory bowel disease "IBD")Accepted[7]IV
Undifferentiated connective tissue disease different from Mixed connective tissue diseaseAcceptedanti-nuclear antibodyHLA-DR4
Undifferentiated spondyloarthropathy
Urticarial vasculitisII?anti C1q antibodies[83]clinically may resemble type I hypersensitivity!
VasculitisAccepted[14]IIIsometimes ANCA
VitiligoSuspected[84][85]NALP-1 RERE, PTPN22, LPP, IL2RA, GZMB, UBASH3A and C1QTNF6
Wegener's granulomatosisAccepted[86]Anti-neutrophil cytoplasmic(cANCA)

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.[87][88][89]

See also[edit]


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