scholarly journals Increased Indoleamine 2,3-Dioxygenase Levels at the Onset of Sjögren’s Syndrome in SATB1-Conditional Knockout Mice

2021 ◽  
Vol 22 (18) ◽  
pp. 10125
Author(s):  
Yuriko Tanaka ◽  
Mayu Onozato ◽  
Tetuo Mikami ◽  
Terumi Kohwi-Shigematsu ◽  
Takeshi Fukushima ◽  
...  
Keyword(s):  
Sjögren’S Syndrome ◽  
Neutralizing Antibodies ◽  
Sjögren's Syndrome ◽  
Keratoconjunctivitis Sicca ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Conditional Knockout ◽  
Indoleamine 2,3 Dioxygenase ◽  
Ifn Γ ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by dysfunction of salivary and lacrimal glands, resulting in xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). Autoantibodies, such as anti-SSA and anti-SSB antibodies, are hallmarks and important diagnostic factors for SS. In our previous study, we demonstrated that SS-like xerostomia was observed in SATB1 conditional knockout (SATB1cKO) mice, in which the floxed SATB1 gene was specifically deleted in hematopoietic cells as early as 4 weeks of age. In these mice, autoantibodies were not detected until 8 weeks of age in SATB1cKO mice, although exocrine gland function reached its lowest at this age. Therefore, other markers may be necessary for the diagnosis of SS in the early phase. Here, we found that mRNA expression of the interferonγ (IFN-γ) gene and the IFN-responsive indoleamine 2,3-dioxygenase (IDO) gene is upregulated in the salivary glands of SATB1cKO mice after 3 and 4 weeks of age, respectively. We detected l-kynurenine (l-KYN), an intermediate of l-tryptophan (l-Trp) metabolism mediated by IDO, in the serum of SATB1cKO mice after 4 weeks of age. In addition, the upregulation of IDO expression was significantly suppressed by the administration of IFN-γ neutralizing antibodies in SATB1cKO mice. These results suggest that the induction of IFN-dependent IDO expression is an initial event that occurs immediately after the onset of SS in SATB1cKO mice. These results also imply that serum l-KYN could be used as a marker for SS diagnosis in the early phases of the disease before autoantibodies are detectable.

scholarly journals Sjogren’s Syndrome Presenting with Solely Cutaneous Features

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1260
Author(s):  
Sneha Centala ◽  
Joyce H. Park ◽  
Diana Girnita
Keyword(s):  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Keratoconjunctivitis Sicca ◽  
Systemic Disease ◽  
Relapsing Polychondritis ◽  
Lymphocytic Infiltration ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Initial Symptom ◽  
Sjögren‘S Syndrome

Sjogren’s syndrome is classically characterized by symptoms of keratoconjunctivitis sicca and xerostomia, secondary to lymphocytic infiltration of the salivary and lacrimal glands. Cutaneous findings of this disease are infrequently discussed and thus rarely considered among patients without the typical symptomatology. However, these patients can develop xerosis, alopecia, vitiligo, papular or nodular lesions, or cutaneous vasculitis. A 56-year-old Asian female presented with intermittent cutaneous erythematous lesions of her bilateral pinna and preauricular areas. Despite initial symptom presentation causing concern for tumid lupus versus cutaneous T cell lymphoma versus relapsing polychondritis, extensive serologic and histopathologic workup eventually indicated a likely diagnosis of Sjogren’s syndrome. This case brings to light that Sjogren’s syndrome is truly a multi-systemic disease and can present with primarily extra glandular cutaneous symptoms. When approaching the workup of a new patient, it is absolutely vital to maintain a broad differential and keep in mind that overlap syndromes among multiple autoimmune diseases do exist as well.

scholarly journals Long term course of tear gland function in patients with keratoconjunctivitis sicca and Sjogren's syndrome

1997 ◽  
Vol 81 (6) ◽  
pp. 435-438 ◽  
Author(s):  
A A Kruize ◽  
O P van Bijsterveld ◽  
R J Hene ◽  
P C M de Wilde ◽  
T E W Feltkamp ◽  
...  
Keyword(s):  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Keratoconjunctivitis Sicca ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Gland Function ◽  
Sjögren‘S Syndrome

scholarly journals Alternative Therapies for Treatment of Keratoconjunctivitis Sicca Associated with Sjorgren's Syndrome

2020 ◽  
pp. 12-22
Author(s):  
Brittney M. Brady ◽  
Michelle K. Man
Keyword(s):  
Case Report ◽  
Sjögren’S Syndrome ◽  
Contact Lens ◽  
Sjögren's Syndrome ◽  
Keratoconjunctivitis Sicca ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Autologous Serum ◽  
Disease Case ◽  
Sjögren‘S Syndrome

Background: Sjogren’s syndrome is a chronic, systemic autoimmune disorder, which often results in significant ocular surface disease. Dry eye associated with Sjogren’s syndrome is a multifactorial disease which leads to decreased function of the lacrimal glands and altered tear composition. There currently are numerous anti-inflammatory methods used for treatment of this disease. Case Report: This case report will focus on the use of amniotic membrane placement and autologous serum tears to facilitate a successful scleral contact lens fit allowing for reduced ocular inflammation and discomfort associated with Keratoconjunctivitis sicca due to Sjogren’s syndrome. Conclusion: Clinical management of keratoconjunctivitis sicca due to Sjogren’s syndrome can be challenging. Diagnosis often requires numerous in office testing including Schirmer I/II, TBUT, sodium fluorescein stain, and osmolarity. Such testing can be repeated over time to monitor for improvement with addition of each new therapy. Various treatment modalities such as topical lubricants, cyclosporine, autologous serum tears, or amniotic membranes have been proven to provide short-term benefits and excellent maintenance of symptoms. Utilizing such treatments to promote an ideal scleral contact lens fit provides lasting benefits of corneal clarity and stable vision.

scholarly journals Immune-Intrinsic Myd88 Directs the Production of Antibodies With Specificity for Extracellular Matrix Components in Primary Sjögren’s Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Jeremy Kiripolsky ◽  
Eileen M. Kasperek ◽  
Chengsong Zhu ◽  
Quan-Zhen Li ◽  
Jia Wang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Primary Sjögren’S Syndrome ◽  
Conditional Knockout ◽  
Primary Sjogren’S Syndrome ◽  
Primary Sjögren's Syndrome ◽  
Sjögren‘S Syndrome

Primary Sjögren’s syndrome is an autoimmune disease that is predominantly seen in women. The disease is characterized by exocrine gland dysfunction in combination with serious systemic manifestations. At present, the causes of pSS are poorly understood. Pulmonary and renal inflammation are observed in pSS mice, reminiscent of a subset of pSS patients. A growing body of evidence indicates that inflammation mediated by Damage-Associated Molecular Patterns (DAMPs) contributes to autoimmunity, although this is not well-studied in pSS. Degraded extracellular matrix (ECM) constituents can serve as DAMPs by binding pattern-recognition receptors and activating Myd88-dependent signaling cascades, thereby exacerbating and perpetuating inflammatory cascades. The ECM components biglycan (Bgn) and decorin (Dcn) mediate sterile inflammation and both are implicated in autoimmunity. The objective of this study was to determine whether these ECM components and anti-ECM antibodies are altered in a pSS mouse model, and whether this is dependent on Myd88 activation in immune cells. Circulating levels of Bgn and Dcn were similar among pSS mice and controls and tissue expression studies revealed pSS mice had robust expression of both Bgn and Dcn in the salivary tissue, saliva, lung and kidney. Sera from pSS mice displayed increased levels of autoantibodies directed against ECM components when compared to healthy controls. Further studies using sera derived from conditional knockout pSS mice demonstrated that generation of these autoantibodies relies, at least in part, on Myd88 expression in the hematopoietic compartment. Thus, this study demonstrates that ECM degradation may represent a novel source of chronic B cell activation in the context of pSS.

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