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.
Multiple Sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by inflammation, demyelination and axonal loss. This disease typically strikes young adults, especially women. There are four types of MS according to their relapsing or progressive pattern that include relapsing-remitting (RRMS), secondary progressive (SPMS), primary progressive (PPMS), and progressive relapsing (PRMS). In most patients, the disease has a relapsing-remitting course during the first years. Within 10 years, approximately 50% of patients progress to SPMS. The aetiology of MS is not well understood, but it is likely multifactorial, combining both genetic and environmental factors. Recently, the literature on the risk factors for MS has grown substantially. They indicate that a combination of a genetic predisposition, exposure to Epstein-Barr virus, cigarette smoking, and reduced sunlight exposure/vitamin D levels is involved. Authorized first-line treatments are considered equally effective, and include interferon beta and glatiramer acetate. They are primarily directed against inflammation, and might fail to adequately control disease activity in some patients. In that case, it has been recommended to switch these patients early to a therapy of higher efficacy. Currently, 13 different drugs with ten different active components are licensed in the European Union (EU) and the United States (US) for the treatment of MS.
Category
Immune system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
08 Diseases of the nervous system
Multiple sclerosis or other white matter disorders
8A40 Multiple sclerosis
H01490 Multiple sclerosis
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06516 TNF signaling
H01490 Multiple sclerosis
Cellular process
nt06527 Necroptosis
H01490 Multiple sclerosis
Immune system
nt06537 TCR/BCR signaling
H01490 Multiple sclerosis
Oksenberg JR, Barcellos LF, Cree BA, Baranzini SE, Bugawan TL, Khan O, Lincoln RR, Swerdlin A, Mignot E, Lin L, Goodin D, Erlich HA, Schmidt S, Thomson G, Reich DE, Pericak-Vance MA, Haines JL, Hauser SL
Title
Mapping multiple sclerosis susceptibility to the HLA-DR locus in African Americans.
