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Genetic associations to germinal centre formation in primary Sjogren's syndrome

Reksten, Tove Ragna; Johnsen, Svein Joar Auglaend; Jonsson, Malin Viktoria; Omdal, Roald; Brun, Johan G.; Theander, Elke LU ; Eriksson, Per; Wahren-Herlenius, Marie; Jonsson, Roland and Nordmark, Gunnel (2014) In Annals of the Rheumatic Diseases 73(6). p.1253-1258
Abstract
Background Primary Sjogren's syndrome (pSS) is an autoimmune rheumatic disease mainly characterised by focal mononuclear cell infiltration in the salivary and lacrimal glands, and by the symptoms xerostomia and keratoconjunctivitis sicca. Germinal centre-like structures (GC) are found in the minor salivary glands of approximately 25% of patients. In this study, we aimed to assess genetic variations in pSS patients with GC-like formations (GC+) compared with patients without such formations (GC-). Methods Minor salivary gland biopsies from Swedish and Norwegian pSS patients (n=320) were evaluated for GC-like formations, identifying 76 GC+ and 244 GC-patients. A panel of 1536 single-nucleotide polymorphisms (SNPs) in 107 genes was genotyped.... (More)
Background Primary Sjogren's syndrome (pSS) is an autoimmune rheumatic disease mainly characterised by focal mononuclear cell infiltration in the salivary and lacrimal glands, and by the symptoms xerostomia and keratoconjunctivitis sicca. Germinal centre-like structures (GC) are found in the minor salivary glands of approximately 25% of patients. In this study, we aimed to assess genetic variations in pSS patients with GC-like formations (GC+) compared with patients without such formations (GC-). Methods Minor salivary gland biopsies from Swedish and Norwegian pSS patients (n=320) were evaluated for GC-like formations, identifying 76 GC+ and 244 GC-patients. A panel of 1536 single-nucleotide polymorphisms (SNPs) in 107 genes was genotyped. Minor allele frequencies in GC+ and GC- patients were compared using Fisher's exact test, and associations were considered significant when p<4.7x10(-4) and suggestive when p<0.01. Results In this case-only analysis, we identified two SNPs in CCL11 (eotaxin) associated with GC-like structures (p<4.7x10(-4), OR 0.45 and 0.41, respectively). A haplotype of the two minor alleles was associated with GC status with p=2.6x10(-4,) OR 0.40. Suggestive associations (p<0.01) were found in SNPs in the B cell activation and/or GC-formation related genes AICDA, BANK1 and BCL2. Furthermore, SNPs in IL17A, ICA1, PKN1 and SNPs in the NF-kappa B pathway genes CARD8, IKBKE and TANK were found suggestively associated with GC-like structures. Conclusions Our findings suggest that genetic variations may explain why ectopic GC-like structures are present in some pSS patients, and support the hypothesis that GC+ and GC- patients represent distinct disease phenotypes. (Less)
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type
Contribution to journal
publication status
published
subject
in
Annals of the Rheumatic Diseases
volume
73
issue
6
pages
1253 - 1258
publisher
British Medical Association
external identifiers
  • wos:000335362100053
  • scopus:84899981675
ISSN
1468-2060
DOI
10.1136/annrheumdis-2012-202500
language
English
LU publication?
yes
id
67b669cf-cf1b-4daf-8cfd-432940567794 (old id 4482329)
date added to LUP
2014-07-01 07:36:35
date last changed
2017-10-01 04:08:59
@article{67b669cf-cf1b-4daf-8cfd-432940567794,
  abstract     = {Background Primary Sjogren's syndrome (pSS) is an autoimmune rheumatic disease mainly characterised by focal mononuclear cell infiltration in the salivary and lacrimal glands, and by the symptoms xerostomia and keratoconjunctivitis sicca. Germinal centre-like structures (GC) are found in the minor salivary glands of approximately 25% of patients. In this study, we aimed to assess genetic variations in pSS patients with GC-like formations (GC+) compared with patients without such formations (GC-). Methods Minor salivary gland biopsies from Swedish and Norwegian pSS patients (n=320) were evaluated for GC-like formations, identifying 76 GC+ and 244 GC-patients. A panel of 1536 single-nucleotide polymorphisms (SNPs) in 107 genes was genotyped. Minor allele frequencies in GC+ and GC- patients were compared using Fisher's exact test, and associations were considered significant when p&lt;4.7x10(-4) and suggestive when p&lt;0.01. Results In this case-only analysis, we identified two SNPs in CCL11 (eotaxin) associated with GC-like structures (p&lt;4.7x10(-4), OR 0.45 and 0.41, respectively). A haplotype of the two minor alleles was associated with GC status with p=2.6x10(-4,) OR 0.40. Suggestive associations (p&lt;0.01) were found in SNPs in the B cell activation and/or GC-formation related genes AICDA, BANK1 and BCL2. Furthermore, SNPs in IL17A, ICA1, PKN1 and SNPs in the NF-kappa B pathway genes CARD8, IKBKE and TANK were found suggestively associated with GC-like structures. Conclusions Our findings suggest that genetic variations may explain why ectopic GC-like structures are present in some pSS patients, and support the hypothesis that GC+ and GC- patients represent distinct disease phenotypes.},
  author       = {Reksten, Tove Ragna and Johnsen, Svein Joar Auglaend and Jonsson, Malin Viktoria and Omdal, Roald and Brun, Johan G. and Theander, Elke and Eriksson, Per and Wahren-Herlenius, Marie and Jonsson, Roland and Nordmark, Gunnel},
  issn         = {1468-2060},
  language     = {eng},
  number       = {6},
  pages        = {1253--1258},
  publisher    = {British Medical Association},
  series       = {Annals of the Rheumatic Diseases},
  title        = {Genetic associations to germinal centre formation in primary Sjogren's syndrome},
  url          = {http://dx.doi.org/10.1136/annrheumdis-2012-202500},
  volume       = {73},
  year         = {2014},
}