Signalling Pathways Identified in Salivary Glands from Primary Sjögren’s Syndrome Patients Reveal Enhanced Adipose Tissue Development, As Demonstrated By Microarray Analysis, Real-Time PCR and Immunohistochemistry

Lara A Aqrawi¹, Janicke C Liaaen Jensen¹, Gunnvor Øijordsbakken², Ann-Kristin Ruus³, Ståle Nygård^4,5, Marit Holden⁶, Roland Jonsson^7,8, Hilde Kanli Galtung⁹ and Kathrine Skarstein^10,11, ¹Department of Oral Surgery and Oral Medicine, University of Oslo, Oslo, Norway, ²Department of Clinical Medicine, University of Bergen, Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway, ³Department of Oral Biology, University of Oslo, Oslo, Norway, ⁴Department of Informatics, University of Oslo, Oslo, Norway, ⁵Bioinformatics core facility, Institute for Cancer research, Oslo University Hospital, Oslo, Norway, ⁶Norwegian Computing Center, Oslo, Oslo, Norway, ⁷Broegelmann Research laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway, ⁸Department of Rheumatology, Haukeland University Hospital, Bergen, Bergen, Norway, ⁹Department of Oral Biology, University of Oslo, Oslo, Pakistan, ¹⁰Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway, ¹¹Department of Pathology, Haukeland University Hospital, Bergen, Bergen, Norway

Meeting: ACR/ARHP Annual Meeting 2017

Date of first publication: September 18, 2017

Keywords: adipose tissue, interleukins (IL) and salivary gland, Sjogren's syndrome

Session Information

Date: Sunday, November 5, 2017

Title: Sjögren's Syndrome Poster I: Translational Research

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: : A characteristic feature of Sjögren’s syndrome (SS) is the destruction of salivary and lacrimal glands mediated by mononuclear cell infiltration. Adipocytes can also occupy a large portion of the salivary gland (SG) tissue area, although little is known about their significance in SS. We have previously investigated adipose tissue infiltration in SG biopsies from SS patients and non-SS sicca controls. Our findings indicated distinct incidence of adipose tissue replacement in SS patients, where adipocytes were detected in IL6 rich regions. We now aimed to examine the development of adipocytes in the SG microenvironment, and delineate their possible involvement in immune reactions.

Methods: A microarray analysis was performed on SG from 6 SS patients and 6 non-SS controls, where the expression levels of genes involved in adipose tissue development were assessed. Real-time PCR was carried out on SG from 14 SS patients and 15 non-SS controls to account for interleukin (IL)-6, IL10 and IL17 mRNA levels. Immunohistochemical staining of frozen SG tissue using IL17 was also conducted.

Results: Upregulated signalling pathways identified in SG of SS patients show prominent adipose tissue development and mitochondrial fatty acid beta-oxidation, including the genes ARID5B, OXCT1, BDH1, SOX8, HMGCS2, FTO, ECHS1, PCCA, ACADL and ACADVL. Genes involved in interferon production and signalling were also detected (IRF1, IRF9, IRF7), in addition to IL6, IL10, and IL17 (Figure 1, Table 1). Higher mRNA levels of IL6, IL17 and IL10 were also observed in the SG of SS patients compared to controls. Moreover, IL17+ cells were observed mostly interstitially in the SG and around adipocytes, also within the focal infiltrates.

Conclusion: Adipocyte development seems to be more prominent in the SG of SS patients at the site of inflammation, where adipose tissue replacement is also evident. Detection of IL17 positive adipocytes in the target organ suggests their involvement in immune reactions.

Disclosure: L. A. Aqrawi, None; J. C. Liaaen Jensen, None; G. Øijordsbakken, None; A. K. Ruus, None; S. Nygård, None; M. Holden, None; R. Jonsson, None; H. K. Galtung, None; K. Skarstein, None.

To cite this abstract in AMA style:

Aqrawi LA, Liaaen Jensen JC, Øijordsbakken G, Ruus AK, Nygård S, Holden M, Jonsson R, Galtung HK, Skarstein K. Signalling Pathways Identified in Salivary Glands from Primary Sjögren’s Syndrome Patients Reveal Enhanced Adipose Tissue Development, As Demonstrated By Microarray Analysis, Real-Time PCR and Immunohistochemistry [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/signalling-pathways-identified-in-salivary-glands-from-primary-sjogrens-syndrome-patients-reveal-enhanced-adipose-tissue-development-as-demonstrated-by-microarray-analysis-real-time-pcr-and/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/signalling-pathways-identified-in-salivary-glands-from-primary-sjogrens-syndrome-patients-reveal-enhanced-adipose-tissue-development-as-demonstrated-by-microarray-analysis-real-time-pcr-and/