Nonendocrine mechanisms of sex bias in rheumatic diseases

Lambert, Nathalie

doi:10.1038/s41584-019-0307-6

Cited by 23 publications

(22 citation statements)

References 203 publications

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“…Although the precise gender ratio differs depending on the study, it is clear that female patients with pSS vastly outnumber male patients, as is true for most other autoimmune diseases. 2 Many gender-related factors, such as X-chromosome-related gene expression, are thought to be associated with female predominance in pSS, but the precise causes of the gender imbalance are not yet fully understood. 3 Most studies on pSS focus on the much larger number of subjects with female gender, and only a few reports have examined the small subset of male patients with pSS.…”

Section: Introductionmentioning

confidence: 99%

“…In addition to sicca symptoms caused by inflammation in exocrine glands, the condition also has diverse extra‐glandular manifestations (EGM). Although the precise gender ratio differs depending on the study, it is clear that female patients with pSS vastly outnumber male patients, as is true for most other autoimmune diseases 2 . Many gender‐related factors, such as X‐chromosome‐related gene expression, are thought to be associated with female predominance in pSS, but the precise causes of the gender imbalance are not yet fully understood 3 .…”

Section: Introductionmentioning

confidence: 99%

“…EULAR, European League Against Rheumatism Autoimmune diseases in general are more likely to affect females. Many previous studies attempting to identify the mechanisms of female predominance in autoimmune diseases have pointed to sex hormones, such as estrogen and androgen, and genetic predispositions including X-linked genes as possible etiologicfactors 2,3. However, although a recent literature suggested that methylation-dependent X-linked gene expression and impaired X-chromosome inactivation could result in differently expressed dose effects of X-chromosome, studies regarding sex hormone are scanty and debatable in terms of pathogenesis of pSS 2,23.…”

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confidence: 99%

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Male patients with primary Sjögren's syndrome: A distinct clinical subgroup?

et al. 2020

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Aim: Because the clinical and immunologic phenotypes of male primary Sjögren's syndrome (pSS) patients have not been fully elucidated, we aimed to investigate the clinical characteristics of male patients with pSS in Korea. Methods: We retrospectively evaluated the medical records of male patients with pSS, who visited Seoul St. Mary's Hospital, a tertiary referral center in Korea, between January, 2015 and December, 2019. Of a total of 1107 patients with pSS, 33 were male, which is a prevalence of 2.9%. These 33 were compared with 353 female patients as a control group, whose records were extracted from the database of the Korean Initiative of Primary Sjögren's Syndrome, our nationwide pSS database. Various clinical aspects were assessed, including secretory functions, extra-glandular manifestations (EGM), disease activity-measuring indices, and hematological and serological variables. Results: Male patients were less likely to complain of xerophthalmia and xerostomia and presented with fewer patient-reported disease outcomes and glandular dysfunctions as compared with female patients. White blood cell and neutrophil counts and the seropositivity of anti-ribonucleoprotein antibody were higher in male patients than in their female counterparts, whereas anti-Ro/SSA antibody and rheumatoid factor were less concentrated in sera from male patients. Pulmonary involvement and lymphoma were seen more frequently in male patients. Among other EGMs, female patients had a higher prevalence of autoimmune thyroid diseases. Conclusions: Male patients with pSS present less severe glandular dysfunctions, better patient-reported disease outcomes, and a higher prevalence of pulmonary involvement and lymphoma compared to females, suggesting distinct clinical phenotypes of pSS.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Male patients with primary Sjögren's syndrome: A distinct clinical subgroup?

et al. 2020

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“…The presence of a second X chromosome, rich in immune-related genes (FOXP3, TLR7, CD40LG, etc. ), correlates with the clinical expression and pathogenesis of systemic autoimmune diseases [6]. The unique characteristics of the X chromosome in terms of inactivation, escaping and skewing are implicated in the pathogenesis of systemic autoimmunity, as reflected in the paradigm of males with Klinefelter syndrome (XXY) who exhibit a 36-fold increase in the risk of developing SS than males without (XY) [7].…”

Section: Introductionmentioning

confidence: 99%

Sjögren’s Syndrome: The Clinical Spectrum of Male Patients

Chatzis

Pezoulas

Ferro

et al. 2020

JCM

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Background: To compare the clinical, serological and histologic features between male and female patients with Sjögren’s syndrome (SS) and explore the potential effect of gender on lymphoma development. Methods: From a multicenter population (Universities of Udine, Pisa and Athens, Harokopion and Ioannina (UPAHI)) consisting of consecutive SS patients fulfilling the 2016 ACR/EULAR criteria, male patients were identified, matched and compared with female controls. Data-driven multivariable logistic regression analysis was applied to identify independent lymphoma-associated factors. Results: From 1987 consecutive SS patients, 96 males and 192 matched female controls were identified and compared. Males had a higher frequency of lymphoma compared to females (18% vs. 5.2%, OR = 3.89, 95% CI: 1.66 to 8.67; p = 0.0014) and an increased prevalence of serum anti-La/SSB antibodies (50% vs. 34%, OR = 1.953, 95% CI: 1.19 to 3.25; p = 0.0128). No differences were observed in the frequencies of lymphoma predictors between the two genders. Data-driven multivariable logistic regression analysis revealed negative association of the female gender with lymphoma and positive association with lymphadenopathy. Conclusion: Male SS patients carry an increased risk of lymphoma development. Although statistics showed no difference in classical lymphoma predictors compared to females, data-driven analysis revealed gender and lymphadenopathy as independent lymphoma-associated features.

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“…In particular, the sole duplication of Tlr7 is sufficient to accellerate autoimmunity. This observation suggests the possible implication of Tlr7 and Yaa in autoimmune disease pathogenesis and deserves to be further elucidated [ 18 ].…”

Section: Innate Immune Cells In Pssmentioning

confidence: 99%

Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation

et al. 2020

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Primary Sjogren Syndrome (pSS) is a complex, multifactorial rheumatic disease that mainly targets salivary and lacrimal glands, inducing epithelitis. The cause behind the autoimmunity outbreak in pSS is still elusive; however, it seems related to an aberrant reaction to exogenous triggers such as viruses, combined with individual genetic pre-disposition. For a long time, autoantibodies were considered as the hallmarks of this disease; however, more recently the complex interplay between innate and adaptive immunity as well as the consequent inflammatory process have emerged as the main mechanisms of pSS pathogenesis. The present review will focus on innate cells and on the principal mechanisms of inflammation connected. In the first part, an overview of innate cells involved in pSS pathogenesis is provided, stressing in particular the role of Innate Lymphoid Cells (ILCs). Subsequently we have highlighted the main inflammatory pathways, including intra- and extra-cellular players. A better knowledge of such processes could determine the detection of new therapeutic targets that are a major need for pSS.

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Nonendocrine mechanisms of sex bias in rheumatic diseases

Cited by 23 publications

References 203 publications

Male patients with primary Sjögren's syndrome: A distinct clinical subgroup?

Male patients with primary Sjögren's syndrome: A distinct clinical subgroup?

Sjögren’s Syndrome: The Clinical Spectrum of Male Patients

Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation

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