Sjögren's syndrome pathophysiology: Difference between revisions
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The [[pathogenesis]] of [[Sjögren's syndrome]] can be linked to both genetic and nongenetic components <ref name="pmid23846338">{{cite journal| author=Mavragani CP, Nezos A, Moutsopoulos HM| title=New advances in the classification, pathogenesis and treatment of Sjogren's syndrome. | journal=Curr Opin Rheumatol | year= 2013 | volume= 25 | issue= 5 | pages= 623-9 | pmid=23846338 | doi=10.1097/BOR.0b013e328363eaa5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23846338 }} </ref>. | The [[pathogenesis]] of [[Sjögren's syndrome]] can be linked to both genetic and nongenetic components <ref name="pmid23846338">{{cite journal| author=Mavragani CP, Nezos A, Moutsopoulos HM| title=New advances in the classification, pathogenesis and treatment of Sjogren's syndrome. | journal=Curr Opin Rheumatol | year= 2013 | volume= 25 | issue= 5 | pages= 623-9 | pmid=23846338 | doi=10.1097/BOR.0b013e328363eaa5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23846338 }} </ref>. | ||
* '''Genetic components:''' | * '''Genetic components:''' | ||
Multiple genes are found to be associated with ُ[[Sjögren's syndrome]]. Evidence suggests genes that encode [[Major histocompatibility complex|Major Histocompatibility Complex]] (MHC), particularly [[Human leukocyte antigen|Human Leukocyte Antigens]] (HLA) genes, play an important role in the disease, although ethnicity seems to affect these roles <ref name="pmid24097067">{{cite journal| author=Lessard CJ, Li H, Adrianto I, Ice JA, Rasmussen A, Grundahl KM et al.| title=Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome. | journal=Nat Genet | year= 2013 | volume= 45 | issue= 11 | pages= 1284-92 | pmid=24097067 | doi=10.1038/ng.2792 | pmc=3867192 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24097067 }}</ref><ref name="pmid24097066">{{cite journal| author=Li Y, Zhang K, Chen H, Sun F, Xu J, Wu Z et al.| title=A genome-wide association study in Han Chinese identifies a susceptibility locus for primary Sjögren's syndrome at 7q11.23. | journal=Nat Genet | year= 2013 | volume= 45 | issue= 11 | pages= 1361-5 | pmid=24097066 | doi=10.1038/ng.2779 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24097066 }}</ref><ref name="pmid8468491">{{cite journal| author=Kang HI, Fei HM, Saito I, Sawada S, Chen SL, Yi D et al.| title=Comparison of HLA class II genes in Caucasoid, Chinese, and Japanese patients with primary Sjögren's syndrome. | journal=J Immunol | year= 1993 | volume= 150 | issue= 8 Pt 1 | pages= 3615-23 | pmid=8468491 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8468491 }}</ref>. Among non-HLA genes, [[TNIP1]], [[IRF5]], [[BLK (gene)|BLK]], [[STAT4]], [[IL12A]], and [[CXCR5]] are all reported to have a significant association <ref name="pmid23857130">{{cite journal| author=Nocturne G, Mariette X| title=Advances in understanding the pathogenesis of primary Sjögren's syndrome. | journal=Nat Rev Rheumatol | year= 2013 | volume= 9 | issue= 9 | pages= 544-56 | pmid=23857130 | doi=10.1038/nrrheum.2013.110 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23857130 }}</ref>. These genes mainly contribute to the activation pathways of several immune signal molecules such as [[Interferon|interferons]] and [[Interleukin|interleukins]], therefore facilitating the immune injury to the susceptible tissues. | Multiple genes are found to be associated with ُ[[Sjögren's syndrome]]. Evidence suggests genes that encode [[Major histocompatibility complex|Major Histocompatibility Complex]] (MHC), particularly [[Human leukocyte antigen|Human Leukocyte Antigens]] (HLA) genes, play an important role in the disease, although ethnicity seems to affect these roles <ref name="pmid24097067">{{cite journal| author=Lessard CJ, Li H, Adrianto I, Ice JA, Rasmussen A, Grundahl KM et al.| title=Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome. | journal=Nat Genet | year= 2013 | volume= 45 | issue= 11 | pages= 1284-92 | pmid=24097067 | doi=10.1038/ng.2792 | pmc=3867192 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24097067 }}</ref><ref name="pmid24097066">{{cite journal| author=Li Y, Zhang K, Chen H, Sun F, Xu J, Wu Z et al.| title=A genome-wide association study in Han Chinese identifies a susceptibility locus for primary Sjögren's syndrome at 7q11.23. | journal=Nat Genet | year= 2013 | volume= 45 | issue= 11 | pages= 1361-5 | pmid=24097066 | doi=10.1038/ng.2779 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24097066 }}</ref><ref name="pmid8468491">{{cite journal| author=Kang HI, Fei HM, Saito I, Sawada S, Chen SL, Yi D et al.| title=Comparison of HLA class II genes in Caucasoid, Chinese, and Japanese patients with primary Sjögren's syndrome. | journal=J Immunol | year= 1993 | volume= 150 | issue= 8 Pt 1 | pages= 3615-23 | pmid=8468491 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8468491 }}</ref>. Among non-HLA genes, [[TNIP1]], [[IRF5]], [[BLK (gene)|BLK]], [[STAT4]], [[IL12A]], and [[CXCR5]] are all reported to have a significant association <ref name="pmid23857130">{{cite journal| author=Nocturne G, Mariette X| title=Advances in understanding the pathogenesis of primary Sjögren's syndrome. | journal=Nat Rev Rheumatol | year= 2013 | volume= 9 | issue= 9 | pages= 544-56 | pmid=23857130 | doi=10.1038/nrrheum.2013.110 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23857130 }}</ref>. These genes mainly contribute to the production and activation pathways of several immune signal molecules such as [[Interferon|interferons]] and [[Interleukin|interleukins]], therefore facilitating the immune injury to the susceptible tissues. | ||
* '''Environmental components:''' | * '''Environmental components:''' | ||
Several studies have indicated an association between Sjögren's syndrome and some [[Virus|viral]] infections. Though the evidence is not definitive yet, both [[Epstein Barr virus|Epstein-Barr Virus (EBV)]] and [[Coxsackie virus|Coxsackie Virus]] are thought to be having a role in causing primary SS. There are also certain types of viruses including [[Human Immunodeficiency Virus (HIV)|HIV]], [[Human T-lymphotropic virus|HTLV-1]] and [[Hepatitis C virus]] that cause SS-like syndromes. | Several studies have indicated an association between Sjögren's syndrome and some [[Virus|viral]] infections. Though the evidence is not definitive yet, both [[Epstein Barr virus|Epstein-Barr Virus (EBV)]] and [[Coxsackie virus|Coxsackie Virus]] are thought to be having a role in causing primary SS. There are also certain types of viruses including [[Human Immunodeficiency Virus (HIV)|HIV]], [[Human T-lymphotropic virus|HTLV-1]] and [[Hepatitis C virus]] that cause SS-like syndromes. | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Farbod Zahedi Tajrishi, M.D.
Overview
ُSjögren's syndrome (SS) is a chronic auto-immune disorder that can affect several organ systems. Both genetic and immune factors contribute to the pathogenesis of the disease. In the most common presentation of the disease, lymphocytes infiltrate the lacrimal and salivary glands and impair their function, hence causing the main characteristic symptoms- dry mouth (keratoconjunctivitis sicca) and eyes (xerostomia). CD4+ T-cells are predominant in mild and moderate salivary gland infiltrations, while B cells play the major role in severe lesions [1].
Pathophysiology
The pathogenesis of Sjögren's syndrome can be linked to both genetic and nongenetic components [2].
- Genetic components:
Multiple genes are found to be associated with ُSjögren's syndrome. Evidence suggests genes that encode Major Histocompatibility Complex (MHC), particularly Human Leukocyte Antigens (HLA) genes, play an important role in the disease, although ethnicity seems to affect these roles [3][4][5]. Among non-HLA genes, TNIP1, IRF5, BLK, STAT4, IL12A, and CXCR5 are all reported to have a significant association [6]. These genes mainly contribute to the production and activation pathways of several immune signal molecules such as interferons and interleukins, therefore facilitating the immune injury to the susceptible tissues.
- Environmental components:
Several studies have indicated an association between Sjögren's syndrome and some viral infections. Though the evidence is not definitive yet, both Epstein-Barr Virus (EBV) and Coxsackie Virus are thought to be having a role in causing primary SS. There are also certain types of viruses including HIV, HTLV-1 and Hepatitis C virus that cause SS-like syndromes.
- Immune-mediated components:
- 1. Lymphocytic infiltration:
The basic mechanism underlying the symptoms of SS involves infiltration of lymphocytes into the exocrine glands. T cells induce apoptosis signals to the glandular epithelial cells, causing them to die and the gland to malfunction.
- 2. Autoantibodies:
References
- ↑ Christodoulou MI, Kapsogeorgou EK, Moutsopoulos HM (2010). "Characteristics of the minor salivary gland infiltrates in Sjögren's syndrome". J Autoimmun. 34 (4): 400–7. doi:10.1016/j.jaut.2009.10.004. PMID 19889514.
- ↑ Mavragani CP, Nezos A, Moutsopoulos HM (2013). "New advances in the classification, pathogenesis and treatment of Sjogren's syndrome". Curr Opin Rheumatol. 25 (5): 623–9. doi:10.1097/BOR.0b013e328363eaa5. PMID 23846338.
- ↑ Lessard CJ, Li H, Adrianto I, Ice JA, Rasmussen A, Grundahl KM; et al. (2013). "Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome". Nat Genet. 45 (11): 1284–92. doi:10.1038/ng.2792. PMC 3867192. PMID 24097067.
- ↑ Li Y, Zhang K, Chen H, Sun F, Xu J, Wu Z; et al. (2013). "A genome-wide association study in Han Chinese identifies a susceptibility locus for primary Sjögren's syndrome at 7q11.23". Nat Genet. 45 (11): 1361–5. doi:10.1038/ng.2779. PMID 24097066.
- ↑ Kang HI, Fei HM, Saito I, Sawada S, Chen SL, Yi D; et al. (1993). "Comparison of HLA class II genes in Caucasoid, Chinese, and Japanese patients with primary Sjögren's syndrome". J Immunol. 150 (8 Pt 1): 3615–23. PMID 8468491.
- ↑ Nocturne G, Mariette X (2013). "Advances in understanding the pathogenesis of primary Sjögren's syndrome". Nat Rev Rheumatol. 9 (9): 544–56. doi:10.1038/nrrheum.2013.110. PMID 23857130.