Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by the production of IgG autoantibodies that are specific for self-antigens, such as DNA, nuclear proteins and certain cytoplasmic components, in association with a diverse array of clinical manifestations. The primary pathological findings in patients with SLE are those of inflammation, vasculitis, immune complex deposition, and vasculopathy. Immune complexes comprising autoantibody and self-antigen is deposited particularly in the renal glomeruli and mediate a systemic inflammatory response by activating complement or via Fc{gamma}R-mediated neutrophil and macrophage activation. Activation of complement (C5) leads to injury both through formation of the membrane attack complex (C5b-9) or by generation of the anaphylatoxin and cell activator C5a. Neutrophils and macrophages cause tissue injury by the release of oxidants and proteases. It has been reported that there is a relatively high genetic component behind SLE. The data of family-based studies point toward an oligogenic background, with several susceptibility genes (SLEB) acting on disease expression along with environmental factors.
Category
Immune system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
04 Diseases of the immune system
Nonorgan specific systemic autoimmune disorders
4A40 Lupus erythematosus
H00080 Systemic lupus erythematosus
Pathway-based classification of diseases [BR:br08402]
Immune system
nt06517 TLR signaling
H00080 Systemic lupus erythematosus
nt06520 CGAS-STING signaling
H00080 Systemic lupus erythematosus
nt06537 TCR/BCR signaling
H00080 Systemic lupus erythematosus
Kyogoku C, Langefeld CD, Ortmann WA, Lee A, Selby S, Carlton VE, Chang M, Ramos P, Baechler EC, Batliwalla FM, Novitzke J, Williams AH, Gillett C, Rodine P, Graham RR, Ardlie KG, Gaffney PM, Moser KL, Petri M, Begovich AB, Gregersen PK, Behrens TW
Title
Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE.
Melki I, Allaeys I, Tessandier N, Mailhot B, Cloutier N, Campbell RA, Rowley JW, Salem D, Zufferey A, Laroche A, Levesque T, Patey N, Rauch J, Lood C, Droit A, McKenzie SE, Machlus KR, Rondina MT, Lacroix S, Fortin PR, Boilard E
Title
FcgammaRIIA expression accelerates nephritis and increases platelet activation in systemic lupus erythematosus.
Lee-Kirsch MA, Gong M, Chowdhury D, Senenko L, Engel K, Lee YA, de Silva U, Bailey SL, Witte T, Vyse TJ, Kere J, Pfeiffer C, Harvey S, Wong A, Koskenmies S, Hummel O, Rohde K, Schmidt RE, Dominiczak AF, Gahr M, Hollis T, Perrino FW, Lieberman J, Hubner N
Title
Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus.
Graham RR, Kozyrev SV, Baechler EC, Reddy MV, Plenge RM, Bauer JW, Ortmann WA, Koeuth T, Gonzalez Escribano MF, Pons-Estel B, Petri M, Daly M, Gregersen PK, Martin J, Altshuler D, Behrens TW, Alarcon-Riquelme ME
Title
A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus.
Zervou MI, Andreou A, Matalliotakis M, Spandidos DA, Goulielmos GN, Eliopoulos EE
Title
Association of the DNASE1L3 rs35677470 polymorphism with systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis: Structural biological insights.
Brown GJ, Canete PF, Wang H, Medhavy A, Bones J, Roco JA, He Y, Qin Y, Cappello J, Ellyard JI, Bassett K, Shen Q, Burgio G, Zhang Y, Turnbull C, Meng X, Wu P, Cho E, Miosge LA, Andrews TD, Field MA, Tvorogov D, Lopez AF, Babon JJ, Lopez CA, Gonzalez-Murillo A, Garulo DC, Pascual V, Levy T, Mallack EJ, Calame DG, Lotze T, Lupski JR, Ding H, Ullah TR, Walters GD, Koina ME, Cook MC, Shen N, de Lucas Collantes C, Corry B, Gantier MP, Athanasopoulos V, Vinuesa CG
Title
TLR7 gain-of-function genetic variation causes human lupus.
Disorders of adaptive immunity [DS:H02526] Primary immunodeficiency disease [DS:H01725]
Description
Autoimmune lymphoproliferative syndromes (ALPS) are autosomal dominant disorders with clinical features of various autoimmune manifestations that predominantly involve polyclonal accumulation of lymphocytes in the spleen and lymph nodes with lymphadenopathy and/or splenomegaly, and expansion of double-negative (DN) T cells in the peripheral blood. Central to the cellular pathogenesis is defective FAS-induced apoptosis, which in turn leads to dysregulation of lymphocyte homeostasis. ALPS caused by heterozygous mutations in the Fas gene (ALPS Type Ia) make up the majority of identified cases. However, other mutations, namely of the FasL gene (ALPS Type Ib) and the caspase 8 and 10 genes (ALPS Type II) are occasionally detected, whereas some patients do not present any known mutations (ALPS-III). Recently, mutations of the NRAS gene have been suggested to cause ALPS Type IV.
Category
Primary immunodeficiency
Brite
Human diseases in ICD-11 classification [BR:br08403]
04 Diseases of the immune system
Primary immunodeficiencies
4A01 Primary immunodeficiencies due to disorders of adaptive immunity
H00108 Autoimmune lymphoproliferative syndromes
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06524 Apoptosis
H00108 Autoimmune lymphoproliferative syndromes
nt06527 Necroptosis
H00108 Autoimmune lymphoproliferative syndromes
Immune system
nt06537 TCR/BCR signaling
H00108 Autoimmune lymphoproliferative syndromes
Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee.
Hashimoto thyroiditis (HT) is a common form of chronic autoimmune thyroid disease (AITD), and is characterized by an inflammatory infiltrate of immunocytes that replace the parenchyma and induce thyroid enlargement, which eventually leads to gland fibrosis. Progressive thyrocyte depletion results in impaired thyroid hormone production and clinical hypothyroidism, a condition that involves a marked reduction of metabolic activity in various cells and tissues. AITDs are regarded as polygenic disorders resulting from the combination of a genetic predisposition in conjunction with an environmental trigger. Two main approaches have been employed to locate susceptibility loci for AITD, namely case control candidate gene studies and genome-wide linkage screens. Case control candidate gene studies have been employed to investigate numerous genes for association with AITD, but to date, only the human leucocyte region (HLA) on chromosome 6p21 and the cytotoxic T lymphocyte associated 4 (CTLA-4) gene on chromosome 2q33 have been consistently shown to be associated with disease.
Category
Immune system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
05 Endocrine, nutritional or metabolic diseases
Endocrine diseases
Disorders of the thyroid gland or thyroid hormones system
5A03 Thyroiditis
H00081 Hashimoto thyroiditis
Pathway-based classification of diseases [BR:br08402]
Immune system
nt06537 TCR/BCR signaling
H00081 Hashimoto thyroiditis
