Editing Sjögren's disease (section)

=== Genetic predisposition ===
The [[genetic locus]] most significantly associated with primary SS is the [[major histocompatibility complex]]/[[human leukocyte antigen]] (MHC/HLA) region, as demonstrated by the preliminary results of the first [[genome-wide association study]].<ref>{{cite journal |last1=Reveille |first1=JD |title=The molecular genetics of systemic lupus erythematosus and Sjögren's disease |journal=Current Opinion in Rheumatology |date=October 1992 |volume=4 |issue=5 |pages=644–56 |pmid=1419498}}</ref> This study included data from a discovery cohort of 395 patients of European ancestry with primary Sjögren's disease, and 1,975 healthy [[Treatment and control groups|control individuals]], and from a replication study that comprised 1,234 cases and 4,779 healthy controls. Associations with [[Polymorphism (biology)|polymorphism]]s located at six independent loci were also detected; ''[[IRF5]], [[STAT4]], [[BLK (gene)|BLK]], [[IL12A]], [[TNIP1]],'' and ''[[CXCR5]]''. This also suggested the activation of the [[innate immune system]], notably through the IFN system, B-cell activation through ''CXCR5''-directed recruitment to [[lymphoid follicles]] and B-cell receptor (BCR) activation involving'' BLK'', and [[T-cell activation]] owing to HLA susceptibility and the IL-12-IFN-γ-axis.<ref name="LessardLi2014">{{cite journal |last1=Lessard |first1=C. J. |last2=Li |first2=H. |last3=Ice |first3=J. A. |last4=Adrianto |first4=I. |last5=Jonsson |first5=R. |last6=Illei |first6=G. G. |last7=Rischmueller |first7=M. |last8=Nordmark |first8=G. |last9=Mariette |first9=X. |last10=Miceli-Richard |first10=C. |last11=Wahren Herlenius |first11=M. |last12=Witte |first12=T. |last13=Brennan |first13=M. |last14=Omdal |first14=R. |last15=Gaffney |first15=P. M. |last16=Lessard |first16=J. A. |last17=Rönnblom |first17=L. |last18=Ng |first18=W.-F. |last19=Rhodus |first19=N. |last20=Segal |first20=B. |last21=Scofield |first21=R. H. |last22=James |first22=J. A. |last23=Anaya |first23=J.-M. |last24=Montgomery |first24=C. G. |last25=Harley |first25=J. B. |last26=Moser Sivils |first26=K. |title=OP0020 Identification of Multiple Sjögren's Syndrome Susceptibility Loci |journal=Annals of the Rheumatic Diseases |date=June 2013 |volume=72 |issue=Suppl 3 |pages=A54.3–A55 |doi=10.1136/annrheumdis-2013-eular.225 |s2cid=84998601 }}</ref>

Patients of different ethnic origins carry different HLA-susceptibility [[allele]]s, of which HLA-DR and HLA-DQ are involved in the pathogenesis of Sjögren's disease. For example, patients from Northern and Western Europe and North America show a high prevalence of ''B8, DRw52,'' and ''DR3'' genes.<ref name="pmid8468491">{{cite journal | vauthors = Kang HI, Fei HM, Saito I, Sawada S, Chen SL, Yi D, Chan E, Peebles C, Bugawan TL, Erlich HA | title = Comparison of HLA class II genes in Caucasoid, Chinese, and Japanese patients with primary Sjögren's syndrome | journal = J. Immunol. | volume = 150 | issue = 8 Pt 1 | pages = 3615–23 | date = April 1993 | doi = 10.4049/jimmunol.150.8.3615 | pmid = 8468491 | s2cid = 1453558 | doi-access = free }}</ref> HLA class II alleles are associated with the presence of specific subsets of [[autoantibodies]], rather than with the disease itself.<ref name="pmid11469461">{{cite journal | vauthors = Bolstad AI, Wassmuth R, Haga HJ, Jonsson R | title = HLA markers and clinical characteristics in Caucasians with primary Sjögren's syndrome | journal = J. Rheumatol. | volume = 28 | issue = 7 | pages = 1554–62 | date = July 2001 | pmid = 11469461 }}</ref> Autoantibodies refer to the loss of B-cell tolerance leading to the production of antibodies directed against diverse organ-specific and organ nonspecific antigens.<ref name=Voulgarelis2010/> Association between HLA and SS is restricted to patients with anti-SSA/Ro or anti-SSB/La antibodies. [[Seropositivity]] for anti-Ro and anti-La is associated with greater severity and longer duration of disease, and findings of their high abundance from the [[salivary glands]] of Sjögren's patients suggests their imperative role in the pathogenesis of SS.<ref name="pmid1685512">{{cite journal | vauthors = Fei HM, Kang H, Scharf S, Erlich H, Peebles C, Fox R | title = Specific HLA-DQA and HLA-DRB1 alleles confer susceptibility to Sjögren's disease and autoantibody production | journal = J. Clin. Lab. Anal. | volume = 5 | issue = 6 | pages = 382–91 | date = 1991 | pmid = 1685512 | doi = 10.1002/jcla.1860050604 | s2cid = 39754064 }}</ref>

Beyond genetics, [[Epigenetics|epigenetic]] abnormality related to [[DNA methylation]], [[histone acetylation]], or [[microRNA]] expression probably has a key role in the pathogenesis of autoimmune diseases, including Sjögren's disease, though research in this area is very limited.<ref>{{cite journal | author = Lu Q | year = 2013 | title = The critical importance of epigenetics in autoimmunity | journal = J. Autoimmun. | volume = 41 | pages = 1–5 | doi=10.1016/j.jaut.2013.01.010| pmid = 23375849 | url = https://tede.ufrrj.br/jspui/handle/jspui/3479 }}</ref>