Current and future treatment in primary Sjögren's syndrome – A still challenging development

Ritter, Jacob; Chen, Yidan; Stefanski, Ana‐Luisa; Dörner, Thomas

doi:10.1016/j.jbspin.2022.105406

Cited by 19 publications

(9 citation statements)

References 60 publications

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“…Primary Sjögren’s syndrome (pSS) is a chronic systemic inflammatory disease characterized by impairment of the lacrimal and salivary glands. Various extraglandular involvements, including the lung, nerve, kidney, skin, musculoskeletal, and hematopoietic systems have been reported 1 . Interstitial lung disease (ILD) is the most frequent pulmonary manifestation in patients with pSS, and ILD can be found in approximately 10–20% of pSS patients.…”

Section: Introductionmentioning

confidence: 99%

Clinical course and risk factors for development and progression of interstitial lung disease in primary Sjögren’s syndrome

Lee

Nam

Hwang

et al. 2023

Sci Rep

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This single-center, retrospective study aimed to investigate the course and prognostic factors of patients with primary Sjögren syndrome-associated interstitial lung disease (pSS-ILD). We included 120 pSS patients who underwent at least two high-resolution computed tomography (HRCT) scans between 2013 and 2021. Clinical symptoms, laboratory data, HRCT findings, and pulmonary function test results were collected. Two thoracic radiologists reviewed the HRCT findings. In patients with pSS without ILD at baseline (n = 81), no development of ILD was found on follow-up (median, 2.8 years). In patients with pSS-ILD (n = 39), total disease extent, extent of coarse reticulation, and traction bronchiectasis increased on HRCT, whereas the extent of ground glass opacity (GGO) decreased at follow-up (median, 3.2 years) (each p < 0.001). In progressive group of pSS-ILD (48.7%), the extent of coarse reticulation and coarseness score of fibrosis were increased at follow-up (p < 0.05). Usual interstitial pneumonia pattern on CT (OR, 15.237) and follow-up duration (OR, 1.403) were independent risk factors for disease progression in patients with pSS-ILD. In both progressive and non-progressive pSS-ILD, GGO decreased, whereas the extent of fibrosis increased even after treatment with glucocorticoid and/or immunosuppressants. In conclusion, progression occurred in approximately half of the pSS-ILD patients with slow gradual deterioration. Our study identified a definite group of progressive pSS-ILD who did not respond to current anti-inflammatory treatment.

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Section: Introductionmentioning

confidence: 99%

Clinical course and risk factors for development and progression of interstitial lung disease in primary Sjögren’s syndrome

Lee

Nam

Hwang

et al. 2023

Sci Rep

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“…16 At present, the therapy of pSS is mainly based on clinical experience and symptomatic treatment, such as alleviating dryness and applying total glucosides of paeony, hydroxychloroquine, and leflunomide to regulate immunity. 2,17 Biological therapy of pSS has a valuable application prospect, but its effectiveness and safety are still controversial. Therefore, it is essential to explore effective potential therapeutic targets for immunotherapy of pSS.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to dry symptoms caused by gland dysfunction, there are also extra‐glandular manifestations, which can be life‐threatening in severe cases, at the same time, these symptoms such as dryness, fatigue, and pain often adversely affect the quality of life in patients 16 . At present, the therapy of pSS is mainly based on clinical experience and symptomatic treatment, such as alleviating dryness and applying total glucosides of paeony, hydroxychloroquine, and leflunomide to regulate immunity 2,17 . Biological therapy of pSS has a valuable application prospect, but its effectiveness and safety are still controversial.…”

Section: Discussionmentioning

confidence: 99%

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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“…(81) In salivary glands of pSS patients CXCR5, CXCR5expressing CD4 T cells, and the chemokine CXCL13 are overexpressed. (58,60,62,68,(82)(83)(84)(85)(86) Increased expression of CXCL13 is associated with increased lymphoid aggregates (foci) in salivary gland tissue and increased organization into ectopic lymphoid structures, and is subsequently associated with increased B cell hyperactivity and lymphoma development. (48,58,60,87) Tfh (T cell)-expressed ICOS, or CD278, is a protein which binds to B cells through its ligand ICOSL (expressed on activated B cells), after which high levels of IL-21 are released and further differentiation of both T cells and B cells is induced.…”

Section: Tfh and Tfh-like Cells Orchestrating Lymphoid Activity And B...mentioning

confidence: 99%

“…Because of its pivotal role in T cell-driven B cell activation targeting ICOS/ICOSL interaction was tested in pSS patients. However, in a phase 2a clinical trial of AMG557/ MEDI5872/Prezalumab (ICOSL) in 32 active patients with pSS (ESSDAI ≥6) the primary endpoint (change in ESSDAI of 3 or more) was not met (ClinicalTrials.gov Identifier NCT02334306, EudraCT Number 2014-003896-41) (83). In different hematological and solid tumors several treatment strategies combining ICOS/ICOSL pathway targeting with anti-CTLA-4 or anti-PD-1/PD-L agents are under investigation for safety and efficacy (84).…”

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confidence: 99%

The role of CCR9-expressing T cell subsets in the immunopathology of primary Sjögren's syndrome

Hinrichs¹

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In this thesis research on CCR9-expressing T cell subsets in primary Sjögren’s syndrome (pSS) is described. pSS is a chronic autoimmune disease in which most patients have complaints of dryness of eyes and mouth, fatigue, and pain in muscles and joints. The dryness arises from inflammation of the glands that produce tear fluid and saliva. This inflammation occurs spontaneously, meaning that the immune system reacts as though an infection with a bacteria or virus needs to be eradicated, whereas this is not the case. In fact, healthy cells of the patient get inflamed and damaged. Research described in this thesis shows that in the blood of patients with pSS different types of T cells that express protein CCR9 are elevated as compared to healthy controls. By far most T cells do not express CCR9. Not only the numbers of CCR9-expressing T cells are elevated in pSS patients, these cells also display more aggressive potential in patients, e.g. by causing more inflammation. Apart from the T cell research, in this thesis we’ve also performed a pilot study to research different autoimmune diseases, as pSS, scleroderma (SSc) and lupus (SLE), using a new minimally-invasive technique. Sebum was sampled from the skin using special tape, after which the sebum was broken into smaller pieces (metabolite ions). Metabolite ions found in the different patient groups were compared to each other and to those from healthy controls. The biggest difference in metabolite ions was found between healthy controls and SSc patients. Furthermore, between patients with SSc and pSS the overlap in aberrant metabolite ions was high. This first study shows potential as new, non-invasive strategy for finding biomarkers in these different disease and will be further studied.

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Current and future treatment in primary Sjögren's syndrome – A still challenging development

Cited by 19 publications

References 60 publications

Clinical course and risk factors for development and progression of interstitial lung disease in primary Sjögren’s syndrome

Clinical course and risk factors for development and progression of interstitial lung disease in primary Sjögren’s syndrome

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

The role of CCR9-expressing T cell subsets in the immunopathology of primary Sjögren's syndrome

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Current and future treatment in primary Sjögren's syndrome – A still challenging development

Cited by 19 publications

References 60 publications

Clinical course and risk factors for development and progression of interstitial lung disease in primary Sjögren’s syndrome

Clinical course and risk factors for development and progression of interstitial lung disease in primary Sjögren’s syndrome

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

The role of CCR9-expressing T cell subsets in the immunopathology 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