scholarly journals POS0109 IDENTIFICATION OF PRIMARY SJOGREN’S SYNDROME SUBTYPES BY MACHINE LEARNING

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 265.2-266
Author(s):  
M. T. Qiu ◽  
S. X. Zhang ◽  
J. Qiao ◽  
J. Q. Zhang ◽  
S. Song ◽  
...  
Keyword(s):  
Machine Learning ◽  
Sjögren’S Syndrome ◽  
Immune Cells ◽  
Immune Cell ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren Syndrome ◽  
Sjogren Syndrome ◽  
Sjögren‘S Syndrome

Background:Sjogren’s syndrome(pSS) is a chronic, progressive, and systematic autoimmune disease characterized by lymphocytic infiltration of exocrine glands 1 2. Sicca symptoms and abnormal fatigue are the main clinical presentation, but those symptoms are non-specific to patients, which lead to delayed diagnosis 1 3. The heterogeneous of clinical manifestation raise challenges regarding diagnosis and therapy in pSS, thus it’s necessary for us to sub-classify pSS.Objectives:To explore new biomarkers for diagnosis and subtypes of pSS based on Machine Learning Primary.Methods:All microarray raw datas (CEL files) were screened and downloaded from Gene Expression Omnibus (GEO). Meta-analysis to identify the consistent DEGs by MetaOmics. Weighted gene co-expression network analysis (WGCNA) was used to the modules related to SS for further analysis. Subclasses were computed using a consensus Non-negative Matrix Factorization (NMF) clustering method. Immune cell infiltration was used to evaluate the expression of immune cells and obtain various immune cell proportions from samples. P value < 0.05 were considered statistically significant. All the analyses were conducted under R environment (version 4.03).Results:A total of 3715 consistent DEGs were identified from the four datasets, including 1748 up-regulated and 1967 down-regulated genes. Tour meaningful modules, including yellow, turquoise, grey60 and bule, were identified (Figure 1A,1B). And 183 overlapping gene were screened from the DEGs and the Hub genes in the four modles for further analysis. We final divided pSS patients into three subtypes, of which yellow and turquoise in Sub1, grey60 in Sub2 and blue in Sub3. Sub1 and Sub3 were related to cell metabolism, while Sub2 had connection with virus infection (Figure 1C,1D). Infiltrated immune cells were also different among these three types (Figure 1E,1F).Conclusion:Patients with pSS could be classified into 3 subtypes, this classification might help for assessing prognosis and guiding precise treatment.References:[1]Ramos-Casals M, Brito-Zerón P, Sisó-Almirall A, et al. Primary Sjogren syndrome. BMJ (Clinical research ed) 2012;344:e3821. doi: 10.1136/bmj.e3821 [published Online First: 2012/06/16].[2]Brito-Zeron P, Baldini C, Bootsma H, et al. Sjogren syndrome. Nat Rev Dis Primers 2016;2:16047. doi: 10.1038/nrdp.2016.47 [published Online First: 2016/07/08].[3]Segal B, Bowman SJ, Fox PC, et al. Primary Sjogren’s Syndrome: health experiences and predictors of health quality among patients in the United States. Health Qual Life Outcomes 2009;7:46. doi: 10.1186/1477-7525-7-46 [published Online First: 2009/05/29].Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared

scholarly journals Oral Disorders in Sjögren’s Syndrome

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Mirjana Sijan Gobeljic ◽  
Vera Milic ◽  
Nada Pejnovic ◽  
Nemanja Damjanov
Keyword(s):  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Oral Candidiasis ◽  
Sjogren’S Syndrome ◽  
Salivary Flow ◽  
Sjogren's Syndrome ◽  
Sjögren Syndrome ◽  
Sjogren Syndrome ◽  
Oral Manifestations ◽  
Sjögren‘S Syndrome

Abstract Sjogren’s syndrome (SS) is a complex, chronic, systemic, autoimmune disease that mainly affects the exocrine glands, especially the salivary and lacrimal glands, leading to the dryness of the mouth and eyes, along with fatigue, joint and muscle pain. The prevalence of SS is estimated to be between 0.05% and 1% in European population. Diagnosis of SS is based on the revised criteria of the American-European consensus group (AECG). Sjogren’s syndrome can be subclassified into primary disease (primary Sjogren syndrome, pSS) and a secondary disease (secondary Sjogren syndrome, sSS) when present with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis. The decrease in salivary flow and qualitative alterations in saliva could explain many of the oral manifestations frequently present in patients with SS. Low salivary flow may affect chewing, swallowing, speech and sleeping in pSS patients. Oral manifestations include dental erosion, dental caries, mucosal infection, ulcers and oral candidiasis. Recent studies reveal that pSS patients experience impaired olfactory and gustatory functions and have higher occurrence of oral complications such as dysgeusia, burning sensation in the tongue (BST) and halitosis. The exocrine manifestations and systemic involvement in SS significantly impact the patient’s perception of oral healthrelated quality of life (OHRQoL).

scholarly journals Contributions of Major Cell Populations to Sjögren’s Syndrome

2020 ◽  
Vol 9 (9) ◽  
pp. 3057 ◽  
Author(s):  
Richard Witas ◽  
Shivai Gupta ◽  
Cuong Q. Nguyen
Keyword(s):  
B Cell ◽  
Sjögren’S Syndrome ◽  
Mouse Models ◽  
Immune Cells ◽  
Immune Cell ◽  
Sjögren's Syndrome ◽  
B Cell Lymphoma ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is a female dominated autoimmune disease characterized by lymphocytic infiltration into salivary and lacrimal glands and subsequent exocrine glandular dysfunction. SS also may exhibit a broad array of extraglandular manifestations including an elevated incidence of non-Hodgkin’s B cell lymphoma. The etiology of SS remains poorly understood, yet progress has been made in identifying progressive stages of disease using preclinical mouse models. The roles played by immune cell subtypes within these stages of disease are becoming increasingly well understood, though significant gaps in knowledge still remain. There is evidence for distinct involvement from both innate and adaptive immune cells, where cells of the innate immune system establish a proinflammatory environment characterized by a type I interferon (IFN) signature that facilitates propagation of the disease by further activating T and B cell subsets to generate autoantibodies and participate in glandular destruction. This review will discuss the evidence for participation in disease pathogenesis by various classes of immune cells and glandular epithelial cells based upon data from both preclinical mouse models and human patients. Further examination of the contributions of glandular and immune cell subtypes to SS will be necessary to identify additional therapeutic targets that may lead to better management of the disease.

scholarly journals AB0431 SALIVARY GLAND ULTRASOUND IN CLINICAL PRACTICE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1514.1-1515
Author(s):  
F. Montero ◽  
K. Carpio ◽  
I. Janta ◽  
J. Molina Collada ◽  
B. Serrano Benavente ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Final Diagnosis ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Primary Sjögren’S Syndrome ◽  
Sjögren Syndrome ◽  
Sjogren Syndrome ◽  
Sjögren‘S Syndrome

Background:Sjogren’s syndrome (SS) is characterized by lymphocytic infiltration of the exocrine glands and marked B-lymphocytic cell hyperreactivity involving a variety of serum autoantibodies.1Salivary Gland Ultrasound (SGU) is a simple, fast, and well- tolerated examination, wich provides information about glandular structure and has proven to be very useful in the Sjögren Syndrome diagnosis2. A prognostic value has also been proposed due to its posible relationship with lymphomas and extra-glandular manifestations.Objectives:The objective of our study is to evaluate ultrasound results in patients who went through an SGU in clinical practice, its usefulness in the diagnosis of Sjögren’s syndrome and the presence of complications (lymphomas, extra-glandular manifestations or factors related to increased lymphoma risk).Methods:We conducted a retrospective cross-sectional study with review of clinical records that included all those patients coded as SGU in the Ultrasound unit of Rheumatology Department from 2016 to December 2019. Information collected included final diagnosis, laboratory results, clinical manifestations and ultrasound results. We performed an analysis on the frequency of pathological SGU and on the relationship between this lesions in patients with final SS diagnosis and the presence of lymphoma, extra-glandular manifestations and the laboratory values related with increased lymphoma risk (low complement levels, cryoglobulinemia, positive autoimmunity).Results:SGU was performed in 171 patients in four years, 162 women (94.7%). The previous diagnoses, reason for the request and final diagnosis are shown in Table 1. The vast majority of the SGU were normal, only 28 (16,3%) were pathological, 13 with a grade II and 8 with a grade III. In the other 7 patients grading was not available. Of the 28 patients with pathological SGU, none had lymphoma, only 3 had recurrent parotitis and 15 had had extra-glandular manifestations, mainly arthralgia / arthritis (12). Only 1 patient, with rheumatoid arthritis, had had a lymphoma and the SGU was normal. Antibody positivity was frequent in pathological SGU, 16/23 antinuclear antibodies, 13/22 anti-Ro and 9/23 rheumatoid factor. Of the 86 patients without previous diagnosis, 18 were diagnosed with Sjogren syndrome, 9 with pathological SGU and the rest were normal. No patient diagnosed with a dry non-autoimmune syndrome presented pathological SGU.Table 1.Previous diagnoses, reason for request and final diagnoses.Previous diagnoses (n: 171)Reason for request (n: 171)Final diagnosis (n: 78)Without prior diagnosis (n: 86)Dry non- autoinmune syndrome (n: 127)Dry non-autoimmune syndrome (n: 60)Primary Sjögren’s syndrome (n: 11)Primary Sjögren’s syndrome (n: 12)Primary Sjögren’s syndrome (n: 18)Systemic Lupus Erythematosus (n: 9)Lymphoma (n: 0)Secondary Sjögren’s syndrome (n: 0)Rheumatoid arthritis (n: 24)Control (n: 13)Other diagnoses (n: 7)Other diagnoses (n: 18)Other reasons (n: 11)Conclusion:The impact of the SGU is low and its use cannot, for now, displace other methods (e.g. salivary gland biopsy) in the diagnosis of SS. Also our low number of patients with pathological SGU together with the low prevalence of the complications studied (e.g. lymphomas = 1) prevents the expected comparisons.References:[1]Ramos-Casals M, Solans R, Rosas J, et al. Primary Sjogren syndrome in Spain: clinical and immunologic expression in 1010 patients. Medicine (Baltimore) 2008; 87: 210–219.[2]Damjanov N, Milic V, Nieto-Gonzalez JC, et al. Multiobserver Reliability of Ultrasound Assessment of Salivary Glands in Patients with Established Primary Sjogren Syndrome. J Rheumatology 2016; 43: 1858–1863.Disclosure of Interests:Fernando Montero: None declared, Karen Carpio: None declared, Iustina Janta: None declared, Juan Molina Collada: None declared, Belén Serrano Benavente: None declared, Julia Martínez-Barrio Consultant of: UCB Pharma, Alfonso Ariza: None declared, Javier Rivera: None declared, Carlos Gonzalez Consultant of: Gilead, Janssen, Novartis,, Speakers bureau: Abbvie, Celgene, Gilead, Janssen, Novartis, Pfizer, Roche, Indalecio Monteagudo: None declared, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi

Sjögren’s syndrome

2020 ◽  
pp. 4532-4537
Author(s):  
Wan-Fai Ng
Keyword(s):  
Sjögren’S Syndrome ◽  
Cell Activation ◽  
Immune Cell ◽  
Sjögren's Syndrome ◽  
Association Studies ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Exocrine Glands ◽  
Lymphocytic Infiltrates ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome is an autoimmune connective tissue disease characterized by dryness of the eyes and mouth and lymphocytic infiltrates in the salivary, lachrymal, and other exocrine glands. Its cause is not known, but it may be primary or associated with other autoimmune diseases (secondary) and it affects women more than men (ratio 9–15:1). The aetiology of SS remains elusive, although genetic susceptibility and environmental triggers both play a role. Genome-wide association studies have identified several disease-susceptibility loci. Infections with various viruses have been associated with an SS-like syndrome. Current evidence suggests that environmental or endogenous antigen triggers immune cell activation and autoantibody production, leading to a self-perpetuating inflammatory response in genetically susceptible individuals, and resulting in destruction of exocrine glands.

Characterization of Immune Cells in Kidneys From Patients With Sjogren's Syndrome

1988 ◽  
Vol 11 (1) ◽  
pp. 20-22 ◽  
Author(s):  
Mark E. Rosenberg ◽  
Paul B. Schendel ◽  
Fred A. McCurdy ◽  
Jeffrey L. Platt
Keyword(s):  
Sjögren’S Syndrome ◽  
Immune Cells ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren‘S Syndrome

scholarly journals Utility of the EULAR Sjögren syndrome disease activity index in Japanese children: a retrospective multicenter cohort study

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Naomi Iwata ◽  
Minako Tomiita ◽  
Ichiro Kobayashi ◽  
Yusaburo Inoue ◽  
Yukiko Nonaka ◽  
...  
Keyword(s):  
Disease Activity ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Primary Sjögren’S Syndrome ◽  
Sjögren Syndrome ◽  
Sjogren Syndrome ◽  
Primary Sjogren’S Syndrome ◽  
Primary Sjögren's Syndrome ◽  
Sjögren‘S Syndrome

Abstract Background The European League Against Rheumatism (EULAR) Sjögren Syndrome Disease Activity Index (ESSDAI) has been utilized to assess Sjögren syndrome-related systemic involvement in adult patients. To date, however, the ESSDAI has not been validated in children with primary Sjögren’s syndrome. This study evaluated the applicability of the ESSDAI to Japanese children with primary Sjögren’s syndrome. Methods The medical records of children who had been diagnosed with Sjogren syndrome at age ≤ 16 years between June 2011 and October 2016 were collected, and their ESSDAIs at initial presentation were calculated. Clinical symptoms and treatment regimens were surveyed by questionnaire, and patients were divided into groups based on ESSDAI and glucocorticoid dosages. The associations of ESSDAI scores with treatment regimens were analyzed statistically. Results The study subjects included 31 children (3 boys, 28 girls) with primary Sjögren’s syndrome. Their median age at disease onset was 10 years (interquartile range [IQR], 8–13 years), and their median initial ESSDAI was 7.0 (IQR; 5.0–15.0). ESSDAI-determined disease activity was high in nine patients (29.0%), moderate in 15 (48.4%), and low in seven (22.6%). During the first year after their initial visit, 14 patients (45.2%) were treated with prednisolone (PSL) and six (19.4%) with immunosuppressants. Dose of PSL was significantly associated with ESSDAI score. Median ESSDAI score was significantly higher in patients treated with high/medium- than with no/low-dose PSL (16.5 [IQR 10.5–18.0] vs 5.0 [IQR 3.0–8.5]). Eight (66.7%) of 12 patients administered medium/high-dose PSL and one (5.3%) of 19 administered no/low-dose PSL had high disease activity on ESSDAI. Conclusion Disease activity assessed by ESSDAI tended to be consistent with disease activity assessed by pediatric rheumatologists in determining treatment regimens. ESSDAI is useful for assessing disease activity in Japanese children with primary Sjögren’s syndrome.

scholarly journals Suppression of age-related salivary gland autoimmunity by glycosylation-dependent galectin-1-driven immune inhibitory circuits

2020 ◽  
Vol 117 (12) ◽  
pp. 6630-6639 ◽  
Author(s):  
Verónica C. Martínez Allo ◽  
Vanesa Hauk ◽  
Nicolas Sarbia ◽  
Nicolás A. Pinto ◽  
Diego O. Croci ◽  
...  
Keyword(s):  
T Cells ◽  
Salivary Gland ◽  
Sjögren’S Syndrome ◽  
Immune Cell ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Lymphoid Cells ◽  
Age Related ◽  
Sjögren‘S Syndrome

Aging elicits quantitative and qualitative changes in different immune components, leading to disruption of tolerogenic circuits and development of autoimmune disorders. Galectin-1 (Gal1), an endogenous glycan-binding protein, has emerged as a regulator of immune cell homeostasis by shaping the fate of myeloid and lymphoid cells. Here, we demonstrate that aged Gal1-null mutant (Lgals1−/−) mice develop a spontaneous inflammatory process in salivary glands that resembles Sjögren’s syndrome. This spontaneous autoimmune phenotype was recapitulated in mice lacking β1,6N-acetylglucosaminyltransferase V (Mgat5), an enzyme responsible for generating β1,6-branched complex N-glycans, which serve as a major ligand for this lectin. Lack of Gal1 resulted in CD11c+dendritic cells (DCs) with higher immunogenic potential, lower frequency of Foxp3+regulatory T cells (Tregs), and increased number of CD8+T cells with greater effector capacity. Supporting its tolerogenic activity, Gal1 expression decreased with age in autoimmunity-prone nonobese diabetic (NOD) mice. Treatment with recombinant Gal1 restored tolerogenic mechanisms and reduced salivary gland inflammation. Accordingly, labial biopsies from primary Sjögren’s syndrome patients showed reduced Gal1 expression concomitant with higher number of infiltrating CD8+T cells. Thus, endogenous Gal1 serves as a homeostatic rheostat that safeguards immune tolerance and prevents age-dependent development of spontaneous autoimmunity.

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