Understanding salivary gland function
“Understanding Salivary Gland Function” is a strategic project aiming at a deeper understanding of salivary gland function with initial emphasis on primary Sjögren’s syndrome (pSS).
Main goals of the research project
- To improve the situation for all groups of patients suffering from dry mouth symptoms and problems, through increased clinical awareness, accurate diagnosis, and better treatment aimed at improving salivary secretion and associated mucous membrane changes and infections.
- To elucidate biomarkers for pSS using advanced investigations of tears and saliva from pSS patients.
SS is an autoimmune connective tissue disorder that mainly affects women from approximately 50 years of age. SS involves dry mouth, dryness of the eyes, fatigue, pain in muscles and joints, significantly impaired quality of life and increased morbidity. The disease is the subject of great attention among clinicians and researchers; nevertheless, the cause is unknown.
It is of significant interest to the individual patient and for the patient group as a whole to achieve improved diagnostics and, thus, possible therapies.
However, decreased salivation and dry mouth are common complaints in the population and may be caused by drug side effects, irradiation against salivary glands, or diseases in salivary glands. The frequency of dry mouth increases with age, mainly due to greater morbidity and drug use in the elderly population.
Very low salivary secretion can impair oral health in the form of dental decay and wear, fungal infections, damage to the mucous membranes, difficulties with speaking and swallowing, and reduced general quality of life.
The Dry Mouth Clinic
The establishment of the Dry Mouth Clinic is an essential element of the overall project. During the fall of 2015, the Dry Mouth Clinic was established at the Institute of Clinical Dentistry through collaboration between resource persons from the departments of surgery, conservative dentistry and gerontology.
- Janicke Liaaen Jensen, project leader, professor
- Bente Brokstad Herlofson, associate professor
- Morten Rykke, professor
- Alix Young Vik, professor
- Lene Hystad Hove, associate professor
- Preet Bano Singh, Post doc
- Lara Aqrawi, associate professor
- Shermin Rusthen, PhD candidate
- Håvard Hynne, PhD candidate
- Julie Frigaard, PhD candidate
Patients and external collaborators
The project requires access to patients with a well-established pSS diagnosis and high competence in the field of dry eyes. pSS patients were identified in the Norwegian Systemic Connective Tissue Disease and Vasculitis Register (NOSVAR), the National Hospital, led by Øyvind Palm and re-examined before referral. In addition, healthy age- and gender-matched controls (negative controls) and patients with sicca symptoms and findings not fulfilling pSS-criteria (non-SS) were examined. The Dry Eye Clinic, led by Tor Paaske Utheim, is the Nordic region's only special clinic dedicated to diagnosis and treatment of dry eyes and performs advanced examinations of eyes and tears using state-of-the-art technology. Furthermore, in collaboration with both Oslo University Hospital and the Department of Biosciences, saliva and tears were closely analysed by size exclusion chromatography and proteomics in order to identify biomarkers for SS that later can be used in diagnosis and therapy. Current research focuses on analyses of cytokines in saliva and tears.
By January 2022, 64 well-characterized pSS patients, 62 healthy controls, 27 non-SS patients, 30 radiated head and neck cancer (HNC) patients and 23 psychiatric patients were recruited and examined at the Dry Mouth Clinic. HNC and psychiatric patients were examined in collaboration with researchers and clinicians from the National Hospital and Lovisenberg Diaconal Hospital, respectively. They were all subjected to questionnaires on general and oral quality of life, as well as xerostomia. Patient history data were collected, the oral mucosa and teeth were closely examined, saliva was collected, and tests on smell and taste were performed. All were also extensively examined at the Dry Eye Clinic. Saliva and tears were subjected to proteomics, metoabolomics, lipidomics and cytokine analyses in order to identify future biomarkers for disease. PhD candidate Håvard Hynne, starting in 2018, works mainly on HNC-patients and advanced biochemical analyses of saliva and tears.
In 2020, two PhD-theses were defended based on papers within the project, namely by Shermin Rusthen and Bek Tashbayev. Also in 2020, a new project on New treatment options for dry mouth based on nanoparticles was initiated in collaboration with Professor Marianne Hiorth, School of Pharmacy with Julie Frigaard, dentist and bioengineer as a new PhD-student.
With time the project will include all categories of patients with dry mouth and/or dry eyes; head and neck cancer, multimorbidity, and multi pharmacy.
Project leader Janicke Liaaen Jensen: email@example.com
- Samuelsen, Tea Marie B; Aqrawi, Lara A.; Skarstein, Kathrine & Jensen, Janicke Liaaen (2021). Evaluering av spyttkjertelbiopsier ved utredning av Sjögrens syndrom. Den norske tannlegeforenings tidende. ISSN 0029-2303. 131, p. 988–994.
- Chen, Xiangjun; Badian, Reza A.; Hynne, Håvard; Amdal, Cecilie Delphin; Herlofson, Bente Brokstad & Utheim, Øygunn Aass [Show all 10 contributors for this article] (2021). Alterations in meibomian glands in patients treated with intensity-modulated radiotherapy for head and neck cancer. Scientific Reports. ISSN 2045-2322. 11:22419, p. 1–7. doi: 10.1038/s41598-021-01844-9. Full text in Research Archive
- Fineide, Fredrik; Chen, Xiangjun; Bjellaas, Thomas; Vitelli, Valeria; Utheim, Tor Paaske & Jensen, Janicke Liaaen [Show all 7 contributors for this article] (2021). Characterization of lipids in saliva, tears and minor salivary glands of sjögren’s syndrome patients using an hplc/ms‐based approach. International Journal of Molecular Sciences. ISSN 1422-0067. 22(16). doi: 10.3390/ijms22168997. Full text in Research Archive
- Dela Cruz, Ariana; Kartha, Vinay; Tilston-Lunel, Andrew; Mi, Rongjuan; Reynolds, Taylor L. & Mingueneau, Michael [Show all 11 contributors for this article] (2021). Gene expression alterations in salivary gland epithelia of Sjögren’s syndrome patients are associated with clinical and histopathological manifestations. Scientific Reports. ISSN 2045-2322. 11, p. 1–12. doi: 10.1038/s41598-021-90569-w. Full text in Research Archive
- Westgaard, Kristine Løken; Hynne, Håvard; Amdal, Cecilie Delphin; Young, Alix; Singh, Preet Bano & Chen, Xiangjun [Show all 12 contributors for this article] (2021). Oral and ocular late effects in head and neck cancer patients treated with radiotherapy. Scientific Reports. ISSN 2045-2322. 11:4026, p. 1–11. doi: 10.1038/s41598-021-83635-w. Full text in Research Archive
- Diep, My Tien; Jensen, Janicke Liaaen; Skudutyte-Rysstad, Rasa; Young, Alix; Sødal, Anne Thea Tveit & Petrovski, Beata [Show all 7 contributors for this article] (2021). Xerostomia and hyposalivation among a 65-yr-old population living in Oslo, Norway. European Journal of Oral Sciences. ISSN 0909-8836. 129(1), p. 1–11. doi: 10.1111/eos.12757.
- Tashbayev, Behzod; Utheim, Tor Paaske; Utheim, Øygunn Aass; Ræder, Sten; Jensen, Janicke Cecilie Liaaen & Yazdani, Mazyar [Show all 10 contributors for this article] (2020). Utility of Tear Osmolarity Measurement in Diagnosis of Dry Eye Disease. Scientific Reports. ISSN 2045-2322. p. 1–7. doi: 10.1038/s41598-020-62583-x. Full text in Research Archive
- Thorlacius, Gudny Ella; Hultin-Rosenberg, Lina; Sandling, Johanna K.; Bianchi, Matteo; Imgenberg-Kreuz, Juliana & Pucholt, Pascal [Show all 32 contributors for this article] (2020). Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome. Rheumatology. ISSN 1462-0324. doi: 10.1093/rheumatology/keaa367.
- Aqrawi, Lara A.; Chen, Xiangjun; Hynne, Håvard; Amdal, Cecilie Delphin; Reppe, Sjur & Aass, Hans Christian Dalsbotten [Show all 14 contributors for this article] (2020). Cytokines Explored in Saliva and Tears from Radiated Cancer Patients Correlate with Clinical Manifestations, Influencing Important Immunoregulatory Cellular Pathways. Cells. ISSN 2073-4409. 9(9). doi: 10.3390/cells9092050. Full text in Research Archive
- Aqrawi, Lara Adnan; Jensen, Janicke Cecilie Liaaen; Fromreide, Siren; Galtung, Hilde Kanli & Skarstein, Kathrine (2020). Expression of NGAL-specific cells and mRNA levels correlate with inflammation in the salivary gland, and its overexpression in the saliva, of patients with primary Sjögren’s syndrome. Autoimmunity. ISSN 0891-6934. s 1- 11 . doi: 10.1080/08916934.2020.1795140 Full text in Research Archive.
Khalafalla, Mahmoud G.; Woods, Lucas T.; Jasmer, Kimberly J.; Forti, Kevin Munoz; Camden, Jean M.; Jensen, Janicke Liaaen; Limesand, Kirsten H.; Galtung, Hilde & Weisman, Gary A. (2020). P2 receptors as therapeutic targets in the salivary gland: From physiology to dysfunction. Frontiers in Pharmacology. ISSN 1663-9812. 11:222, s 1- 223 . doi: 10.3389/fphar.2020.00222
Tashbayev, Behzod; Garen, Torhild Oddveig; Palm, Øyvind; Chen, Xiangjun; Herlofson, Bente Brokstad; Young Vik, Alix Rosslyn; Hove, Lene Hystad; Rykke, Morten; Singh, Preet Bano; Aqrawi, Lara Adnan; Utheim, Øygunn Aass; Utheim, Tor Paaske & Jensen, Janicke Cecilie Liaaen (2020). Patients with non-Sjögren's sicca report poorer general and oral health-related quality of life than patients with Sjögren's syndrome: a cross-sectional study. Scientific Reports. ISSN 2045-2322. . doi: 10.1038/s41598-020-59078-0 Full text in Research Archive.
Aqrawi, Lara A.; Galtung, Hilde; Guerreiro, Eduarda; Øvstebø, Reidun; Thiede, Bernd; Utheim, Tor Paaske; Chen, Xiangjun; Utheim, Øygunn Aass; Palm, Øyvind; Skarstein, Kathrine & Jensen, Janicke Liaaen (2019). Proteomic and histopathological characterisation of sicca subjects and primary Sjögren’s syndrome patients reveals promising tear, saliva and extracellular vesicle disease biomarkers. <https://www.odont.uio.no/iko/english/people/aca/jljensen/index.html#vrtx-publication-tab-2> Arthritis Research & Therapy http://arthritis-research.com/. ISSN 1478-6362. 21 . doi: https://doi.org/10.1186/s13075-019-1961-4
Chen, Xiangjun; Aqrawi, Lara Adnan; Utheim, Tor Paaske; Tashbayev, Behzod; Utheim, Øygunn Aass; Reppe, Sjur; Hove, Lene Hystad; Herlofson, Bente Brokstad; Singh, Preet Bano; Palm, Øyvind; Galtung, Hilde & Jensen, Janicke Liaaen (2019). Elevated cytokine levels in tears and saliva of patients with primary Sjögren's syndrome correlate with clinical ocular and oral manifestations.. Scientific Reports . ISSN 2045-2322. 9(1). doi:10.1038/s41598-019-43714-5 http://dx.doi.org/10.1038/s41598-019-43714-5
Rusthen, Shermin; Kristoffersen, Anne Karin; Young, Alix; Galtung, Hilde; Petrovski, Beata; Palm, Øyvind; Enersen, Morten & Jensen, Janicke Liaaen (2019). Dysbiotic salivary microbiota in dry mouth and primary Sjögren’s syndrome patients. PLoS ONE <http://www.plosone.org/> . ISSN 1932-6203. 14(6), s 1- 15 . doi:10.1371/journal.pone.0218319 <http://dx.doi.org/10.1371/journal.pone.0218319>
Singh, Preet Bano; Young, Alix; Homayouni, Amin; Hove, Lene Hystad; Petrovski, Beata; Herlofson, Bente Brokstad; Palm, Øyvind; Rykke, Morten & Jensen, Janicke Liaaen (2019). Distorted Taste and Impaired Oral Health May Affect Nutritional Status in Patients with Sicca Complaints. Nutrients <http://www.mdpi.com/journal/nutrients> . ISSN 2072-6643. 11(2) . doi:10.3390/nu11020264 <http://dx.doi.org/10.3390/nu11020264>
Aqrawi, Lara Adnan; Chen, Xiangjun; Jensen, Janicke Liaaen; Morthen, Mathias Kaurstad; Thiede, Bernd; Utheim, Øygunn Aass; Palm, Øyvind; Tashbayev, Behzod; Utheim, Tor Paaske & Galtung, Hilde (2018). Severity of clinical dry eye manifestations influences protein expression in tear fluid of patients with primary Sjögren's syndrome. PLoS ONE <http://www.plosone.org/> . ISSN 1932-6203. 13:e0205762(10), s 1- 14 . doi: 10.1371/journal.pone.0205762 <http://dx.doi.org/10.1371/journal.pone.0205762>
Aqrawi, Lara Adnan; Jensen, Janicke Liaaen; Øijordsbakken, Gunnvor; Ruus, Ann-Kristin; Nygård, Ståle; Holden, Marit; Jonsson, Roland; Galtung, Hilde & Skarstein, Kathrine (2018). Signalling pathways identified in salivary glands from primary Sjögren's syndrome patients reveal enhanced adipose tissue development. Autoimmunity. ISSN 0891-6934. 51(3), s 135- 146 . doi: 10.1080/08916934.2018.1446525
Nesvold, Marianne; Jensen, Janicke Liaaen; Hove, Lene Hystad; Singh, Preet Bano; Young, Alix; Palm, Øyvind; Andersen, Lene Frost; Carlsen, Monica Hauger & Iversen, Per Ole (2018). Dietary intake, body composition and oral health parameters among female patients with primary Sjögren’s syndrome. Nutrients. ISSN 2072-6643. 10(866) . doi: 10.3390/nu10070866
Tashbayev, Behzod; Rusthen, Shermin; Young, Alix; Herlofson, Bente Brokstad; Hove, Lene Hystad; Singh, Preet Bano; Rykke, Morten; Aqrawi, Lara A.; Chen, Xiangjun; Utheim, Øygunn Aass; Utheim, Tor Paaske; Palm, Øyvind & Jensen, Janicke Liaaen (2017). Comprehensive Oral and Ocular Evaluation of Patients with Primary Sjögren’s Syndrome.. Scientific Reports. ISSN 2045-2322. . doi: doi: 10.1038/s41598-017-10809-w
Rusthen, Shermin; Young, Alix; Herlofson, Bente Brokstad; Aqrawi, Lara A.; Rykke, Morten; Hove, Lene Hystad; Palm, Øyvind; Jensen, Janicke Liaaen & Singh, Preet Bano (2017). Oral disorders and oral health-related quality of life in patients with primary Sjögren’s Syndrome.. European Journal of Oral Sciences. ISSN 0909-8836. 00, s 1- 7
Chen, Xiangjun; Utheim, Øygunn Aass; Xiao, J.; Stojanovic, A; Tashbayev, Behzod; Jensen, Janicke Liaaen & Utheim, Tor Paaske (2017). Meibomian gland features in a Norwegian cohort of patients with primary Sjögren´s syndrome.. PLoS ONE. ISSN 1932-6203. . doi: 10.1371/journal.pone.0184284
Aqrawi, Lara A.; Galtung, Hilde; Vestad, Beate; Øvstebø, Reidun; Thiede, Bernd; Rusthen, Shermin; Young, Alix; Guerreiro, Eduarda; Utheim, TP; Chen, X; Utheim, Øa; Palm, Øivind & Jensen, Janicke Liaaen (2017). Identification of potential saliva and tear biomarkers in primary Sjögren’s syndrome, utilising the extraction of extracellular vesicles and proteomics analysis. Arthritis Research & Therapy. ISSN 1478-6362. . doi: 10.1186/s13075-017-1228-x
Skarstein K, Aqrawi LA, Øijordsbakken G, Jonsson R, Jensen JL. Adipose tissue is prominent in salivary glands of Sjögren's syndrome patients and appears to influence the microenvironment in these organs. 2016, 20:1-9. [Epub ahead of print]