Autoimmune disease

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

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]

Criteria[edit]

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]

  • Direct evidence from transfer of pathogenic antibody or pathogenic T cells
  • Indirect evidence based on reproduction of the autoimmune disease in experimental animals
  • Circumstantial evidence from clinical clues
  • Genetic architecture clustering with other autoimmune diseases

Effects[edit]

It has been estimated that autoimmune diseases are among the 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 eighty illnesses caused by autoimmunity.[5]

Classification[edit]

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.

Name: Accepted/
suspected
Hypersensitivity

I, II, III, IV

Autoantibody Notes
Acute disseminated encephalomyelitis (ADEM) Accepted[7]
Addison's disease interferon omega; transglutaminase; aromatic acid carboxylase; GAD; HAI; 17 hydroxylase; 21 hydroxylase
Agammaglobulinemia IGHM; IGLL1: CD79A; CD79B; BLNK; LRRC8A
Alopecia areata Accepted[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 Spondylitis Suspected[10][11] CD8; HLA-B27
Antiphospholipid syndrome Accepted[7] anti-cardiolipin;anti pyruvate dehydrogenase; β2 glycoprotein I; phosphatidylserine; anti apoH; Annexin A5 HLA-DR7, HLA-B8, HLA-DR2, HLA-DR3
Antisynthetase syndrome
Atopic allergy I
Atopic dermatitis I
Autoimmune aplastic anemia
Autoimmune cardiomyopathy Accepted
Autoimmune enteropathy
Autoimmune hemolytic anemia Accepted II complement activation
Autoimmune hepatitis Accepted cell-mediated anti-mitochondrial antibodies; ANA; anti-smooth muscle antibodies, LKM-1; soluble liver antigen
Autoimmune inner ear disease Accepted [12]
Autoimmune lymphoproliferative syndrome Accepted TNFRSF6; defective Fas-CD95 apoptosis
Autoimmune peripheral neuropathy Accepted
Autoimmune pancreatitis Accepted ANA; anti-lactoferrin antibodiesanti-carbonic anhydrase antibodies; rheumatoid factor
Autoimmune polyendocrine syndrome Accepted Unknown or multiple APS-1 see Addison's disease
Autoimmune progesterone dermatitis Accepted
Autoimmune thrombocytopenic purpura Accepted anti gpIIb-IIIa or 1b-IX
Autoimmune urticaria Accepted [13]
Autoimmune uveitis Accepted HLAB-27?
Balo disease/Balo concentric sclerosis
Behçet's disease Accepted immune-mediated systemic vasculitis; linkage to HLA-B51 (HLA-B27); very different manifestations with ulcers as common symptom; also called Morbus Adamandiades-Behçet
Berger's disease IgA (elevated in 50% of patients), IgA (in mesangial deposits on kidney biopsy)
Bickerstaff's encephalitis Anti-GQ1b 2/3 patients similar to Guillain-Barré syndrome
Blau syndrome overlaps both sarcoidosis and granuloma annulare
Bullous pemphigoid IgG autoantibodies targeting the type XVII collagen component of hemidesmosomes [14]
Cancer
Castleman's disease Over expression of IL-6
Celiac disease Accepted[15][16][17] IV?? Anti-tissue transglutaminase antibodies anti-endomysial IgA, anti-gliadin IgA HLA-DQ8 and DQ2.5
Chagas disease Suspected[18]
Chronic inflammatory demyelinating polyneuropathy Anti-ganglioside antibodies:anti-GM1, anti-GD1a, anti-GQ1b similar to Guillain-Barré syndrome
Chronic recurrent multifocal osteomyelitis LPIN2, D18S60,similar to Majeed syndrome
Chronic obstructive pulmonary disease Suspected[19][20]
Churg-Strauss syndrome p-ANCA Eosinophilia[21]
Cicatricial pemphigoid anti-BP-1, anti BP-2 precipitates C3
Cogan syndrome
Cold agglutinin disease Accepted II IgM idiopathic or secondary to leukemia or infection
Complement component 2 deficiency
Contact dermatitis IV
Cranial arteritis aka Temporal arteritis; involves giant cells
CREST syndrome Anti-centromere antibodies Anti-nuclear antibodies
Crohn's disease Immune related[22] IV Innate immunity; Th17; Th1; ATG16L1; CARD15;XBP1;
Cushing's Syndrome cortisol binding globulin?
Cutaneous leukocytoclastic angiitis neutrophils
Dego's disease Vasculopathy
Dercum's disease Suspected Lipoid tissue.[23]
Dermatitis herpetiformis IgA Eosinophilia;[21] anti-epidermal transglutaminase antibodies
Dermatomyositis Accepted[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 1 Accepted[7] IV Glutamic acid decarboxylase antibodies (GADA), islet cell antibodies (ICA), and insulinoma-associated autoantibodies (IA-2), anti-insulin antibodies HLA-DR3, HLA-DR4
Diffuse cutaneous systemic sclerosis anti-nuclear antibodies, anti-centromere and anti-scl70/anti-topoisomerase antibodies[26] COL1A2 and TGF-β1
Dressler's syndrome myocardial neo-antigens formed as a result of the MI
Drug-induced lupus Anti-histone antibodies
Discoid lupus erythematosus III IL-2 and IFN-gamma>[27]
Eczema LEKTI, SPINK5,[28] filaggrin.,[29] Brain-derived neurotrophic factor (BDNF) and Substance P.[30]
Endometriosis Suspected[31]
Enthesitis-related arthritis[32] . MMP3[33] TRLR2, TLR4,[34] ERAP1[35]
Eosinophilic fasciitis Accepted
Eosinophilic gastroenteritis IgE IL-3, IL-5, GM-CSF, eotaxin
Eosinophilic pneumonia
Epidermolysis bullosa acquisita COL7A1
Erythema nodosum
Erythroblastosis fetalis II ABO, Rh, Kell antibodies mother's immune system attacks fetus
Essential mixed cryoglobulinemia
Evan's syndrome
Fibrodysplasia ossificans progressiva ACVR1 Lymphocytes express increased BMP4
Fibrosing alveolitis (or Idiopathic pulmonary fibrosis) SFTPA1, SFTPA2, TERT, and TERC.[36]
Gastritis serum antiparietal and anti-IF antibodies
Gastrointestinal pemphigoid Accepted
Glomerulonephritis Sometimes IgA see Buerger's disease for IgA; Membranous glomerulonephritis for IgG; Membranoproliferative/mesangiocapillary GN (Complement activation); Goodpasture's syndrome; Wegener's granulomatosis
Goodpasture's syndrome Accepted[7] II Anti-Basement Membrane Collagen Type IV Protein
Graves' disease Accepted[7] II thyroid autoantibodies (TSHR-Ab) that activate the TSH-receptor (TSHR)
Guillain-Barré syndrome (GBS) Accepted[7] IV Anti-ganglioside
Hashimoto's encephalopathy Accepted[7] IV alpha-enolase[37]
Hashimoto's thyroiditis Accepted[7] IV antibodies against thyroid peroxidase and/or thyroglobulin HLADR5, CTLA-4
Henoch-Schonlein purpura immunoglobulin A (IgA) and complement component 3 (C3)
Herpes gestationis aka Gestational Pemphigoid IgG and C3 misdirected antibodies intended to protect the placenta
Hidradenitis suppurativa Suspected[38]
Hughes-Stovin syndrome
Hypogammaglobulinemia IGHM, IGLL1, CD79A, BLNK, LRRC8A, CD79B
Idiopathic inflammatory demyelinating diseases a variant of multiple sclerosis
Idiopathic pulmonary fibrosis SFTPA1, SFTPA2, TERT, and TERC.[36]
Idiopathic thrombocytopenic purpura (See Autoimmune thrombocytopenic purpura) Accepted[7] II glycoproteins IIb-IIIa or Ib-IX, immunoglobulin G
IgA nephropathy III? IgA produced from marrow rather than MALT
Inclusion body myositis similar to polymyositis but does not respond to steroid therapy-activated T8 cells
Chronic inflammatory demyelinating polyneuropathy anti-ganglioside antibodies similar to Guillain–Barré syndrome
Interstitial cystitis Suspected[39] Mast cells
Juvenile idiopathic arthritis aka Juvenile rheumatoid arthritis inconsistent ANA Rheumatoid factor
Kawasaki's disease Suspected ITPKC HLA-B51
Lambert-Eaton myasthenic syndrome voltage-gated calcium channels; Q-type calcium channel, synaptogagmin, muscarinic acetylcholine receptor M1 HLA-DR3-B8
Leukocytoclastic vasculitis
Lichen planus
Lichen sclerosus
Linear IgA disease (LAD)
Lupoid hepatitis aka Autoimmune hepatitis ANA 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 erythematosus Accepted[7] III Anti-nuclear antibodies[43] anti-Ro.[44] Also, they are often present in Sjögren's syndrome.[45][46]Eosinophilia[21]
Majeed syndrome LPIN2
Ménière's disease III? major peripheral myelin protein P0[47]
Microscopic polyangiitis p-ANCA myeloperoxidase binds to neutrophils causing them to degranulate and damages endothelium
Miller-Fisher syndrome see Guillain-Barre Syndrome Accepted anti-GQ1b
Mixed connective tissue disease Accepted[7] anti-nuclear antibody anti-U1-RNP HLA-DR4
Morphea Suspected[48]
Mucha-Habermann disease aka Pityriasis lichenoides et varioliformis acuta T-cells
Multiple sclerosis Accepted[49] IV Anti-Kir4.1 (heterogeneous)[49] Autoantibody against potasium channel. Also invoved HLA-DR2, PECAM-1[50] Anti-myelin basic protein
Myasthenia gravis Accepted[7] II nicotinic acetylcholine receptor MuSK protein HA-B8 HLA-DR3 HLA-DR1
Microscopic colitis Suspected
Myositis see Dermatomyositis and Polymyositis see Inclusion-body-myositis
Narcolepsy[51][52] Accepted II? hypocretin or orexin[53] HLA-DQB1*0602[54]
Neuromyelitis optica (also Devic's disease) II? NMO-IgG aquaporin 4.[55][56]
Neuromyotonia Suspected[57] II? voltage-gated potassium channels.[57]
Occular cicatricial pemphigoid II? BP-1, BP-2 C3 deposition
Opsoclonus myoclonus syndrome Suspected IV? Lymphocyte recruitment to CSF[58]
Ord's thyroiditis
Palindromic rheumatism anti-cyclic citrullinated peptide antibodies (anti-CCP) and antikeratin antibodies (AKA)[59]
PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcus) Suspected II? antibodies against streptococcal infection serve as auto-antibodies
Paraneoplastic cerebellar degeneration IV?[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 syndrome ANA
Parsonage-Turner syndrome
Pars planitis
Pemphigus vulgaris Accepted[7] II Anti-Desmoglein 3 eosinophilia[21]
Pernicious anaemia Accepted[63] II anti-parietal cell antibody
Perivenous encephalomyelitis
POEMS syndrome interleukin 1β, interleukin 6 and TNFα. vascular endothelial growth factor (VEGF), given the .[64]
Polyarteritis nodosa
Polymyalgia rheumatica
Polymyositis Accepted[24] IFN-gamma, IL-1, TNF-alpha
Primary biliary cirrhosis Accepted[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 cholangitis HLA-DR52a overlap with primary biliary cirrhosis?
Progressive inflammatory neuropathy Suspected
Psoriasis Accepted[66] IV? CD-8 T-cells, HLA-Cw6, IL-12b, IL-23b, TNFalpha, NF-κB
Psoriatic arthritis Accepted[67] IV? HLA-B27
Pyoderma gangrenosum Can occur in conjunction with other immune-related disorders
Pure red cell aplasia
Rasmussen's encephalitis anti-NR2A antibodies
Raynaud phenomenon Suspected Can occur in conjunction with other immune-related disorders
Relapsing polychondritis Accepted[68]
Reiter's syndrome
Restless leg syndrome Suspected May occur in Sjögren's syndrome, celiac disease, and rheumatoid arthritis or in derangements of iron metabolism
Retroperitoneal fibrosis
Rheumatoid arthritis Accepted[7] III Rheumatoid factor (anti-IgGFc), Anti-MCV, ACPAs(Vimentin HLA-DR4, PTPN22, depleted B cells, TNF alpha, IL-17, (also maybe IL-1, 6, and 15)
Rheumatic fever Accepted[69] II streptococcal M protein cross reacts with human myosin,[70]
Sarcoidosis Suspected IV[71][72] BTNL2; HLA-B7-DR15; HLA DR3-DQ2.[73]
Schizophrenia Suspected[74][75][76]
Schmidt syndrome another form of APS anti-21 hydroxylase, anti-17 hydroxylase[77] DQ2, DQ8 and DRB1*0404
Schnitzler syndrome IgM?
Scleritis
Scleroderma Suspected[48] IV? Scl-70 Anti-topoisomerase dysregulated apoptosis?
Serum Sickness III
Sjögren's syndrome Accepted[7] anti-Ro.[44] Also, they are often present in Sjögren's syndrome.[45][46]
Spondyloarthropathy HLA-B27
Still's disease see Juvenile Rheumatoid Arthritis ANA macrophage migration inhibitory factor[78]
Stiff person syndrome Suspected glutamic acid decarboxylase (GAD),[79] GLRA1 (glycine receptor)
Subacute bacterial endocarditis (SBE) III [80] essential mixed cryoglobulinemia
Susac's syndrome
Sweet's syndrome GCSF
Sydenham chorea see PANDAS
Sympathetic ophthalmia ocular antigens following trauma
Systemic lupus erythematosus see Lupus erythematosus III
Takayasu's arteritis
Temporal arteritis (also known as "giant cell arteritis") Accepted[7] IV
Thrombocytopenia II glycoproteins 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 NAIT multiple mechanisms
Tolosa-Hunt syndrome
Transverse myelitis Accepted Transverse Myelitis is a rare neurological disorder that is part of a spectrum of neuroimmunologic diseases of the central nervous system. http://www.myelitis.org/
Ulcerative colitis (one of two types of idiopathic inflammatory bowel disease "IBD") Accepted[7] IV
Undifferentiated connective tissue disease different from Mixed connective tissue disease Accepted anti-nuclear antibody HLA-DR4
Undifferentiated spondyloarthropathy
Urticarial vasculitis II? anti C1q antibodies[83] clinically may resemble type I hypersensitivity!
Vasculitis Accepted[14] III sometimes ANCA
Vitiligo Suspected[84][85] NALP-1 RERE, PTPN22, LPP, IL2RA, GZMB, UBASH3A and C1QTNF6
Wegener's granulomatosis Accepted[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]

References[edit]

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