Activation of Akt Signaling Pathway in the Minor Salivary Glands of Patients with Primary Sjögren’s Syndrome Does Not Relate with Clinical Phenotype

Ioanna Stergiou¹, Loukas Chatzis², Asimina Papanikolaou³, Stavroula Giannouli⁴, Athanasios Tzioufas², Michael Voulgarelis² and Efstathia Kapsogeorgou², ¹Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, ²Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece, ³Department of Haemopathology, "Evangelismos" Hospital, Athens, Greece, Athens, Greece, ⁴2nd Department of Internal Medicine, Hippokrateion Hospital, National and Kapodistrian University of Athens, Athens, Greece, Athens, Greece

Meeting: ACR Convergence 2021

Keywords: Sjögren's syndrome

Session Information

Date: Saturday, November 6, 2021

Title: Sjögren's Syndrome – Basic & Clinical Science Poster (0296–0322)

Session Type: Poster Session A

Session Time: 8:30AM-10:30AM

Background/Purpose: Akt is a phosphoinositide-dependent serine/threonine kinase with diverse regulatory functions that has been implicated in numerous pathological processes, including oncogenesis and autoimmune diseases. Indirect lines of evidence suggest that this pathway may be implicated in pathogenesis of primary Sjögren’s syndrome (pSS). The purpose of this study is to investigate the expression and activation of Akt kinase pathway in different clinical phenotypes of pSS and related lymphomagenesis.

Methods: The expression of the entire protein, the threonine 308-phosphorylated Akt kinase and serine 473-phosphorylated Akt kinase, as well as substrates PRAS40 and FoxO1 (total and phosphorylated forms), which are phosphorylated by Akt, were evaluated by immunohistochemistry in minor salivary glands (MSG) of pSS patients (n=29), non-SS sicca-complaining individuals with negative biopsy (sicca-controls; n=10) and gastric biopsies from patients with MALT lymphoma associated with Helicobacter pylori infection (n=5). Sicca-controls and gastric MALT lymphomas served as control goups. The pSS patients group included 10 at low risk for lymphoma development, 10 at high-risk [four of whom, namely pre-lymphoma, developed lymphoma 7.46 years (median time to lymphoma diagnosis, range 2.0-15.5 years) after the MSG biopsy], and 9 with pSS-associated lymphoma.

Results: The phosphorylated forms of Akt, PRAS40 and FoxO1 were strongly detected in the epithelia and all infiltrating mononuclear cells at the MSGs of 27 pSS patients and stomachs of all patients with gastric lymphoma. Low staining was detected in two pSS patients and two sicca-controls. The rest sicca-controls were negative for all molecules. The activation of Akt pathway was not associated with a higher risk for lymphoma development, lymphoma or other disease features.

Conclusion: Our findings disclosed a strong activation of the Akt/mammalian target of rapamycin (mTOR) pathway in MSGs of pSS patients, independently of their clinical phenotype suggesting a role in disease pathogenesis.

Disclosures: I. Stergiou, None; L. Chatzis, None; A. Papanikolaou, None; S. Giannouli, None; A. Tzioufas, None; M. Voulgarelis, None; E. Kapsogeorgou, None.

To cite this abstract in AMA style:

Stergiou I, Chatzis L, Papanikolaou A, Giannouli S, Tzioufas A, Voulgarelis M, Kapsogeorgou E. Activation of Akt Signaling Pathway in the Minor Salivary Glands of Patients with Primary Sjögren’s Syndrome Does Not Relate with Clinical Phenotype [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/activation-of-akt-signaling-pathway-in-the-minor-salivary-glands-of-patients-with-primary-sjogrens-syndrome-does-not-relate-with-clinical-phenotype/. Accessed .

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