Sex differences in Sjögren’s syndrome: a comprehensive review of immune mechanisms

Brandt, Jessica; Priori, Roberta; Valesini, Guido; Fairweather, DeLisa

doi:10.1186/s13293-015-0037-7

Cited by 99 publications

(110 citation statements)

References 136 publications

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“…(Christian et al, 2009; Ford and Stowe, 2013; Glaser et al, 1991; Stowe et al, 2010) Because depression(Andersson et al, 2015; Euesden et al, 2017) and EBV(Niller et al, 2008) are both linked to certain autoimmune disorders (e.g. systemic lupus erythematosus) known to occur more frequently in females,(Brandt et al, 2015; Dunn et al, 2015; Ngo et al, 2014) further research testing causal pathways and the role of sex hormones in EBV reactivation and immune irregularities among adolescents is warranted.…”

Section: 0 Discussionmentioning

confidence: 99%

Depressive symptoms are associated with salivary shedding of Epstein-Barr virus in female adolescents: The role of sex differences

Ford

Stowe

2017

Psychoneuroendocrinology

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Background Adolescent females have a higher prevalence of depression in comparison to their male peers - a disparity that has been increasing over the past decade. Depression is of concern as it is associated with chronic disease and to immune dysregulation, which may be one mechanism linking depression to future pathology. This study examined the extent to which sex moderated the association between depressive symptoms and immune dysregulation during adolescence using Epstein-Barr virus (EBV) reactivation, a biomarker of cellular immune response, as a model. Methods A representative community sample of 259 female and 279 male adolescents aged 11 to 17 years who were EBV IgG positive were examined. Trained interviewers collected the data during two home visits, one week apart. Depressive symptoms were measured at the first visit using the 9 item short-form of the Center for Epidemiologic Studies-Depression scale. EBV biomarkers were collected via saliva at the second visit and included a qualitative measure of EBV viral capsid antigen immunoglobulin G to assess prior EBV infection and a quantitative measure of EBV DNA to assess the number of viral copies shed in the saliva. Results In multivariable logistic regression analyses, increasing depressive symptoms were significantly associated with salivary shedding of EBV DNA for adolescent females only (logit=0.66, se=0.30, p<0.05), and the interaction between sex and depressive symptoms on salivary shedding of EBV DNA was statistically significant (logit= −1.19, se=0.42, p<0.01). Sensitivity analyses were conducted in which sex was examined as a moderator in the relationship between depressive symptoms and salivary EBV DNA quantitative copies via Tobit regression; results were consistent with the presented findings. Conclusions Depressive symptoms are associated with EBV reactivation among EBV positive female adolescents, but not males. Future research is needed to examine EBV reactivation in female adolescents as a mechanism linking depression to future chronic disease and the role of sex hormones in explaining sex differences in the relationship between depressive symptoms and EBV reactivation.

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Section: 0 Discussionmentioning

confidence: 99%

Depressive symptoms are associated with salivary shedding of Epstein-Barr virus in female adolescents: The role of sex differences

Ford

Stowe

2017

Psychoneuroendocrinology

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“…One of the primary clinical features of SS is that the disease is closely linked to sex, with roughly 90% of cases being diagnosed among females 3,4 ; however, no underlying sexual differences have been identified that might account for the degree to which females are more vulnerable to the disease. Specifically, only vague and largely descriptive references to hormonal differences have been offered to date 64‐66 . The data shown here offers an indication of potential underlying mechanisms that may help shed light on the vastly differing disease patterns between sex.…”

Section: Discussionmentioning

confidence: 98%

Sex‐mediated elevation of the specialized pro‐resolving lipid mediator levels in a Sjögren's syndrome mouse model

Parashar

Schulte²,

Hardt

et al. 2020

FASEB j.

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Our previous results showed that the specialized pro‐resolving mediator (SPM) Resolvin D1 (RvD1) promotes resolution of inflammation in salivary glands in non‐obese diabetic (NOD)/ShiLtJ, a mouse model for Sjögren's syndrome (SS). Additionally, mice lacking the RvD1 receptor ALX/FPR2 show defective innate and adaptive immune responses in salivary glands. Particularly, ALX/FPR2 KO mice exhibit exacerbated inflammation in their salivary glands in response to systemic LPS treatment. Moreover, female ALX/FPR2 KO mice show increased autoantibody production and loss of salivary gland function with age. Together, these studies suggest that an underlying SPM dysregulation could be contributing to SS progression. Therefore, we investigated whether SPM production is altered in NOD/ShiLtJ using metabololipidomics and enzyme‐linked immunosorbent assay (ELISA). Our results demonstrate that SPM levels were broadly elevated in plasma collected from NOD/ShiLtJ female mice after disease onset, whereas these drastic changes did not occur in male mice. Moreover, gene expression of enzymes involved in SPM biosynthesis were altered in submandibular glands (SMG) from NOD/ShiLtJ female mice after disease onset, with 5‐LOX and 12/15‐LOX being downregulated and upregulated, respectively. Despite this dysregulation, the abundances of the SPM products of these enzymes (ie, RvD1 and RvD2) were unaltered in freshly isolated SMG cells suggesting that other cell populations (eg, lymphocytes) may be responsible for the overabundance of SPMs that we observed. The elevation of SPMs noted here appeared to be sex mediated, meaning that it was observed only in one sex (females). Given that SS primarily affects females (roughly 90% of diagnosed cases), these results may provide some insights into the mechanisms underlying the observed sexual dimorphism.

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“…According to the National Institute of Health (NIH), 1 systemic autoimmune diseases (SADs) affect 23.5 million people in United States (prevalence of 8%). The proportion of primary Sjogren's syndrome (pSS) among patients affected by systemic autoimmune diseases (SADs) remains debated, but prevalence of the disease is estimated around 0.05%.…”

Section: Introductionmentioning

confidence: 99%

Pathogenesis-based treatments in primary Sjogren's syndrome using artificial intelligence and advanced machine learning techniques: a systematic literature review

Redou

Gal

Rouvière

et al. 2018

Human Vaccines & Immunotherapeutics

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Big data analysis has become a common way to extract information from complex and large datasets among most scientific domains. This approach is now used to study large cohorts of patients in medicine. This work is a review of publications that have used artificial intelligence and advanced machine learning techniques to study physio pathogenesis-based treatments in pSS. A systematic literature review retrieved all articles reporting on the use of advanced statistical analysis applied to the study of systemic autoimmune diseases (SADs) over the last decade. An automatic bibliography screening method has been developed to perform this task. The program called BIBOT was designed to fetch and analyze articles from the pubmed database using a list of keywords and Natural Language Processing approaches. The evolution of trends in statistical approaches, sizes of cohorts and number of publications over this period were also computed in the process. In all, 44077 abstracts were screened and 1017 publications were analyzed. The mean number of selected articles was 101.0 (S.D. 19.16) by year, but increased significantly over the time (from 74 articles in 2008 to 138 in 2017). Among them only 12 focused on pSS but none of them emphasized on the aspect of pathogenesis-based treatments. To conclude, medicine progressively enters the era of big data analysis and artificial intelligence, but these approaches are not yet used to describe pSS-specific pathogenesis-based treatment. Nevertheless, large multicentre studies are investigating this aspect with advanced algorithmic tools on large cohorts of SADs patients.

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Sex differences in Sjögren’s syndrome: a comprehensive review of immune mechanisms

Cited by 99 publications

References 136 publications

Depressive symptoms are associated with salivary shedding of Epstein-Barr virus in female adolescents: The role of sex differences

Depressive symptoms are associated with salivary shedding of Epstein-Barr virus in female adolescents: The role of sex differences

Sex‐mediated elevation of the specialized pro‐resolving lipid mediator levels in a Sjögren's syndrome mouse model

Pathogenesis-based treatments in primary Sjogren's syndrome using artificial intelligence and advanced machine learning techniques: a systematic literature review

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