Update on disease pathogenesis, diagnosis, and management of primary Sjögren’s syndrome

Wang, Jing; Zhou, Lingyan; Liu, Bin

doi:10.1111/1756-185x.13839

Cited by 28 publications

(23 citation statements)

References 35 publications

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“…SS is a disease resulting in progressive destruction of exocrine salivary and lacrimal gland tissue. The major clinical characteristics are xerostomia and xeropthalmia in addition to fatigue and various other symptoms, which may also affect other organ systems ( 127 , 128 ). Patients most often have ANAs and characteristic AuAbs are Ro60 and La Abs, but various other AuAbs may also be present.…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr Virus and Systemic Autoimmune Diseases

2021

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Epstein-Barr Virus (EBV) is an extremely successful human herpes virus, which infects essentially all human beings at some time during their life span. EBV infection and the associated immune response results in production of antibodies (seroconversion), which occurs mainly during the first years of life, but may also happen during adolescence or later in life. Infection of adolescents can result in infectious mononucleosis, an acute serious condition characterized by massive lymphocytosis. Transmission of EBV mainly occurs through saliva but can rarely be spread through semen or blood, e.g. through organ transplantations and blood transfusions. EBV transmission through oral secretions results in infection of epithelial cells of the oropharynx. From the epithelial cells EBV can infect B cells, which are the major reservoir for the virus, but other cell types may also become infected. As a result, EBV can shuttle between different cell types, mainly B cells and epithelial cells. Moreover, since the virus can switch between a latent and a lytic life cycle, EBV has the ability to cause chronic relapsing/reactivating infections. Chronic or recurrent EBV infection of epithelial cells has been linked to systemic lupus erythematosus and Sjögren’s syndrome, whereas chronic/recurrent infection of B cells has been associated with rheumatoid arthritis, multiple sclerosis and other diseases. Accordingly, since EBV can shuttle between epithelial cells and B cells, the systemic autoimmune diseases often occur as overlapping syndromes with symptoms and characteristic autoantibodies (e.g. antinuclear antibodies and rheumatoid factors) reflecting epithelial and/or B cell infection.

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Section: Introductionmentioning

confidence: 99%

Epstein-Barr Virus and Systemic Autoimmune Diseases

2021

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“…Symptomatic treatments for hyposalivation are limited to the use of saliva substitutes with modest effectiveness, and salivary secretory agonists that only provide temporary relief. 8 Due to the significant unmet medical need, and the limitations of current therapies, the development of novel treatments to decrease inflammation and restore salivary gland secretory function is essential. RvD1 is a novel therapeutic for The shaded region represents the 90% prediction interval for the simulated RvD1 concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…SS has a profound negative impact on the quality of life, 6 and, unfortunately, no effective treatment exists. Symptomatic treatments for hyposalivation are limited to the use of saliva substitutes with modest effectiveness, and salivary secretory agonists that only provide temporary relief 8 . Due to the significant unmet medical need, and the limitations of current therapies, the development of novel treatments to decrease inflammation and restore salivary gland secretory function is essential.…”

Section: Discussionmentioning

confidence: 99%

“…8 A state of chronic inflammation causes tissue damage followed by cytokine and chemokine release. 8 When resolution mechanisms are working correctly, neutrophils and M2 macrophages can clear the site of injury or infection. 9 However, in SS these resolution mechanisms are impaired 10 , and the dead cells involved in the process cannot be removed from the injury/infection site leading to the production of autoantigens and elevations in proinflammatory cytokine levels.…”

Section: Accepted Articlementioning

confidence: 99%

“…Viral and bacterial infections, in conjunction with the activation of susceptibility genes, stimulates chronic salivary gland inflammation 8 . A state of chronic inflammation causes tissue damage followed by cytokine and chemokine release 8 . When resolution mechanisms are working correctly, neutrophils and M2 macrophages can clear the site of injury or infection 9 .…”

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confidence: 99%

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Predicting Resolvin D1 Pharmacokinetics in Humans with Physiologically‐Based Pharmacokinetic Modeling

Yellepeddi

Parashar

Dean

et al. 2020

Clinical Translational Sci

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Sjögren's syndrome (SS) is an autoimmune disease with no effective treatment options. Resolvin D1 (RvD1) belongs to a class of lipid-based specialized pro-resolving mediators that showed efficacy in preclinical models of SS. We developed a physiologically-based pharmacokinetic (PBPK) model of RvD1 in mice and optimized the model using plasma and salivary gland pharmacokinetic (PK) studies performed in NOD/ShiLtJ mice with SS-like features. The predictive performance of the PBPK model was also evaluated with two external datasets from the literature reporting RvD1 PKs. The PBPK model adequately captured the observed concentrations of RvD1 administered at different doses and in different species. The PKs of RvD1 in virtual humans were predicted using the verified PBPK model at various doses (0.01-10 mg/kg). The first-inhuman predictions of RvD1 will be useful for the clinical trial design and translation of RvD1 as an effective treatment strategy for SS.

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The proportion of CD161 on CD56⁺ NK cells in peripheral circulation associates with clinical features and disease activity of primary Sjögren's syndrome

Zhao,

Yang,

Song

et al. 2024

Immunity Inflam & Disease

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ObjectivesThe purpose of this study was to examine the proportion of CD161 on CD56+ natural killer (NK) cells in peripheral blood of primary Sjögren's syndrome (pSS) and investigate its clinical relevance of pSS.MethodsThe proportion of CD56+ NK cells and CD161 on CD56+ NK cells was detected by flow cytometry in 31 pSS patients and 29 healthy controls (HCs). The correlations between the proportion of CD161+CD56+ NK cells and clinical features and disease activity of pSS were further analyzed. Meanwhile, we drew the receiver operating characteristic curve to evaluate the diagnostic value of CD161+CD56+ NK cells in pSS. In addition, we evaluated the differences in the effects of CD161+ cells and CD161− cells in peripheral blood on the function of CD56+ NK cells in 5 pSS patients.ResultsThe proportion of CD56+ NK cells and CD161+CD56+ NK cells decreased markedly in pSS patients compared to HCs. The correlation analysis showed that the proportion of CD161+CD56+ NK cells negatively correlated with white blood cells, Immunoglobulin A (IgA), IgM, IgG, European League Against Rheumatism Sjogren's Syndrome Patient Reported Index and European League Against Rheumatism Sjogren's Syndrome Disease Activity Index, and positively correlated with complement C4. The proportion of CD161+CD56+ NK cells in pSS patients with decayed tooth, fatigue, arthralgia, skin involvement, primary biliary cirrhosis, interstitial lung disease, anti‐SSA/Ro60 positive, anti‐SSB positive and high IgG was lower than that in negative patients. Furthermore, compared with inactive patients, the proportion of CD161+CD56+ NK cells decreased obviously in active patients. The area under the curve was 0.7375 (p = .0016), the results indicated that CD161+CD56+ NK cells had certain diagnostic values for pSS. In addition, the proportion of CD86, HLA‐DR, Ki67, FasL, TNF‐α, and IFN‐γ on CD161+CD56+ NK cells was lower than that on CD161−CD56+ NK cells in the peripheral blood of pSS patients.ConclusionThis study suggested that the proportion of CD56+ NK cells and CD161+CD56+ NK cells decreased significantly in pSS patients, and the proportion of CD161+CD56+ NK cells negatively associated with the clinical features and disease activity of pSS patients. CD161 expression inhibited the function of CD56+ NK cells in peripheral blood of pSS patients. The CD161+CD56+ NK cells may present as a potential target for therapy and a biomarker of disease activity in pSS.

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Update on disease pathogenesis, diagnosis, and management of primary Sjögren’s syndrome

Cited by 28 publications

References 35 publications

Epstein-Barr Virus and Systemic Autoimmune Diseases

Epstein-Barr Virus and Systemic Autoimmune Diseases

Predicting Resolvin D1 Pharmacokinetics in Humans with Physiologically‐Based Pharmacokinetic Modeling

The proportion of CD161 on CD56⁺ NK cells in peripheral circulation associates with clinical features and disease activity of primary Sjögren's syndrome

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Update on disease pathogenesis, diagnosis, and management of primary Sjögren’s syndrome

Cited by 28 publications

References 35 publications

Epstein-Barr Virus and Systemic Autoimmune Diseases

Epstein-Barr Virus and Systemic Autoimmune Diseases

Predicting Resolvin D1 Pharmacokinetics in Humans with Physiologically‐Based Pharmacokinetic Modeling

The proportion of CD161 on CD56+ NK cells in peripheral circulation associates with clinical features and disease activity of primary Sjögren's syndrome

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The proportion of CD161 on CD56⁺ NK cells in peripheral circulation associates with clinical features and disease activity of primary Sjögren's syndrome