Page 763 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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Sjögren Syndrome

Sarfaraz A. Hasni, Leyla Y. Teos, Ilias Alevizos

Sjögren syndrome (SS) is a chronic systemic autoimmune disease viral infections, may lead to epithelial cell activation that triggers
characterized by lachrymal and salivary gland dysfunction. It a protracted inflammatory response with features of autoim-
was named after the Swedish ophthalmologist Henrik Sjögren munity. Autoreactive lymphocytes and autoantibodies are
after he published a report of 19 cases of keratoconjunctivitis considered important in this process, although the pathogenic
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in 1933. The hallmark feature of SS is deficient tear and saliva role of any particular autoantibody is still undefined. 4
production as a result of lymphocytic infiltration of the salivary
and lachrymal glands leading to xerostomia (dry mouth) and Immunogenetic Factors
xerophthalmia (dry eyes). In addition, SS can involve any organ SS is associated with certain human leukocyte antigen (HLA)
system and present with a wide spectrum of clinical features. class II haplotypes. Initial reports of HLA class II associations
The autoimmune process seems to primarily affect the lining described enrichment of DR3 and DR2 in European populations
epithelium of various organs; in fact, some experts have proposed of patients with primary SS. This genetic association predomi-
the term “autoimmune epithelitis” to be used instead of SS. 2 nantly involves antibody-positive but not antibody-negative
patients with SS. Several genetic polymorphisms previously linked
to other autoimmune diseases are also associated with SS. Among
KEY CONCEPTS these, two transcription factors, STAT4 (signal transducer and
activator of transcription 4) and IRF5 (interferon [IFN] regulatory
• Sjögren syndrome (SS) is one of the most common autoimmune factor 5), which were both independently associated with SS,
diseases, mainly affecting females. It targets the salivary and lachrymal showed an additive effect, increasing the risk of SS from around
glands, causing xerostomia and xerophthalmia. 1.6–1.9 for one risk allele to 6.7 when both risk alleles were
• The diagnosis of SS is complex and requires a multidisciplinary team present. 5
for the assessment of oral, ocular, and systemic manifestations.
• Anti-Ro/SSA and Anti-La/SSB autoantibodies are encountered in Although the individual gene approach has successfully
approximately 70% of patients with SS. Significantly increased incidence identified genes associated with SS, two large-scale genome-wide
of congenital heart block is present in the offspring of Anti-Ro/Anti-La association studies have increased the number of genetic loci
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positive mothers. that function as potential risk factors. A study by Lessard et al.
• The risk of lymphoma is significantly higher in patients with SS, and genotyped more than 10 000 patients with SS and control subjects
this risk increases over time. of European descent and found seven genetic loci to be signifi-
• Currently, there is only palliative treatment for alleviation of the cantly associated with SS. These loci included the following genes:
symptoms of SS.
MHC-II, IRF5, STAT4, IL-12A, BLK, CXCR5, and TNIP1. A second
large-scale study examined DNA variations from approximately
1700 patients with SS and controls subjects from Han, China,
EPIDEMIOLOGY and identified a new gene associated with SS, the transcription
factor GTF2I located in 7q21. However, the odds ratio for GTF2I
SS predominantly affects females (female-to-male ratio 9 : 1) in was a moderate 2.2. 8
their fourth and fifth decades of life. However, symptoms can
be present for a much longer time, and there is usually a 5- to Environmental Factors
10-year delay in the diagnosis of SS. The reported prevalence of The inciting etiopathogenic event in SS is not known, and it
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SS varies widely from 0.1% to 4.8%. This variation may result may not be a single event. The strong predominance of females
from the use of different classification criteria, geographical and suggests gender-specific predisposing factors. Although sex
environmental influences, and varying study sizes and target hormones are of obvious interest, there is no conclusive proof
populations. When a more strict definition is applied to the that the difference in the pathogenesis between males and females
available data, the true prevalence of SS is estimated to be around can be attributed to sex hormones alone. Overall, estrogens are
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1%, making it the second most common systemic rheumatic considered contributors to autoimmunity, whereas androgens
disease after rheumatoid arthritis (RA). are thought to be protective.
Viral infections have also been proposed as inciting events. This
IMMUNOPATHOGENESIS theory is supported by the observation that chronic inflammation
of the salivary glands occurs with chronic hepatitis C, human
The pathogenesis of SS is largely unknown. In a genetically T-lymphotropic virus 1 (HTLV-1), and human immunodeficiency
predisposed individual, various environmental factors, such as virus (HIV) infections, and such infections cause a disease with a

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