Browsing by Author "Lieberman, Scott M."

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    Childhood Sjögren syndrome: features of an international cohort and application of the 2016 ACR/EULAR classification criteria
    (Oxford University Press, 2021) Basiaga, Matthew L.; Stern, Sara M.; Mehta, Jay J.; Edens, Cuoghi; Randell, Rachel L.; Pomorska, Anna; Irga-Jaworska, Ninela; Ibarra, Maria F.; Bracaglia, Claudia; Nicolai, Rebecca; Susic, Gordana; Boneparth, Alexis; Srinivasalu, Hemalatha; Dizon, Brian; Kamdar, Ankur A.; Goldberg, Baruch; Knupp-Oliveira, Sheila; Antón, Jordi; Mosquera, Juan M.; Appenzeller, Simone; O'Neil, Kathleen M.; Protopapas, Stella A.; Saad-Magalhães, Claudia; Akikusa, Jonathan D.; Thatayatikom, Akaluck; Cha, Seunghee; Nieto-González, Juan Carlos; Lo, Mindy S.; Brennan Treemarcki, Erin; Yokogawa, Naoto; Lieberman, Scott M.; Childhood Arthritis and Rheumatology Research Alliance and the International Childhood Sjögren Syndrome Workgroup; Pediatrics, School of Medicine
    Objective: Sjögren syndrome in children is a poorly understood autoimmune disease. We aimed to describe the clinical and diagnostic features of children diagnosed with Sjögren syndrome and explore how the 2016 ACR/EULAR classification criteria apply to this population. Methods: An international workgroup retrospectively collected cases of Sjögren syndrome diagnosed under 18 years of age from 23 centres across eight nations. We analysed patterns of symptoms, diagnostic workup, and applied the 2016 ACR/EULAR classification criteria. Results: We identified 300 children with Sjögren syndrome. The majority of patients n = 232 (77%) did not meet 2016 ACR/EULAR classification criteria, but n = 110 (37%) did not have sufficient testing done to even possibly achieve the score necessary to meet criteria. Even among those children with all criteria items tested, only 36% met criteria. The most common non-sicca symptoms were arthralgia [n = 161 (54%)] and parotitis [n = 140 (47%)] with parotitis inversely correlating with age. Conclusion: Sjögren syndrome in children can present at any age. Recurrent or persistent parotitis and arthralgias are common symptoms that should prompt clinicians to consider the possibility of Sjögren syndrome. The majority of children diagnosed with Sjögren syndromes did not meet 2016 ACR/EULAR classification criteria. Comprehensive diagnostic testing from the 2016 ACR/EULAR criteria are not universally performed. This may lead to under-recognition and emphasizes a need for further research including creation of paediatric-specific classification criteria.
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    Sex Effects on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome
    (ARVO, 2018-11-01) Tellefsen, Sara; Morthen, Mathias Kaurstad; Richards, Stephen M.; Lieberman, Scott M.; Darabad, Raheleh Rahimi; Kam, Wendy R.; Sullivan, David A.; Anesthesia, School of Medicine
    Purpose: Sjögren syndrome is an autoimmune disease that occurs primarily in women, and is associated with lacrimal gland inflammation and aqueous-deficient dry eye. We hypothesize that sex-associated differences in lacrimal gland gene expression are very important in promoting lymphocyte accumulation in this tissue and contribute to the onset, progression, and/or severity of the inflammatory disease process. To test our hypothesis, we explored the nature and extent of sex-related differences in gene expression in autoimmune lacrimal glands. Methods: Lacrimal glands were collected from age-matched, adult, male and female MRL/MpJ-Tnfrsf6lpr (MRL/lpr) and nonobese diabetic/LtJ (NOD) mice. Glands were processed for the analysis of differentially expressed mRNAs by using CodeLink Bioarrays and Affymetrix GeneChips. Data were evaluated with bioinformatics and statistical software. Results: Our results show that sex significantly influences the expression of thousands of genes in lacrimal glands of MRL/lpr and NOD mice. The immune nature of this glandular response is very dependent on the Sjögren syndrome model. Lacrimal glands of female, as compared with male, MRL/lpr mice contain a significant increase in the expression of genes related to inflammatory responses, antigen processing, and chemokine pathways. In contrast, it is the lacrimal tissue of NOD males, and not females, that presents with a significantly greater expression of immune-related genes. Conclusions: These data support our hypothesis that sex-related differences in gene expression contribute to lacrimal gland disease in Sjögren syndrome. Our findings also suggest that factors in the lacrimal gland microenvironment are critically important in mediating these sex-associated immune effects.
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    Testosterone Influence on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome
    (Association for Research in Vision and Ophthalmology, 2019-05) Morthen, Mathias Kaurstad; Tellefsen, Sara; Richards, Stephen M.; Lieberman, Scott M.; Rahimi Darabad, Raheleh; Kam, Wendy R.; Sullivan, David A.; Anesthesia, School of Medicine
    Purpose: Sjögren syndrome is an autoimmune disorder that occurs almost exclusively in women and is associated with extensive inflammation in lacrimal tissue, an immune-mediated destruction and/or dysfunction of glandular epithelial cells, and a significant decrease in aqueous tear secretion. We discovered that androgens suppress the inflammation in, and enhance the function of, lacrimal glands in female mouse models (e.g., MRL/MpJ-Tnfrsf6lpr [MRL/lpr]) of Sjögren syndrome. In contrast, others have reported that androgens induce an anomalous immunopathology in lacrimal glands of nonobese diabetic/LtJ (NOD) mice. We tested our hypothesis that these hormone actions reflect unique, strain- and tissue-specific effects, which involve significant changes in the expression of immune-related glandular genes. Methods: Lacrimal glands were obtained from age-matched, adult, female MRL/lpr and NOD mice after treatment with vehicle or testosterone for up to 3 weeks. Tissues were processed for analysis of differentially expressed mRNAs using CodeLink Bioarrays and Affymetrix GeneChips. Data were analyzed with bioinformatics and statistical software. Results: Testosterone significantly influenced the expression of numerous immune-related genes, ontologies, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in lacrimal glands of MRL/lpr and NOD mice. The nature of this hormone-induced immune response was dependent upon the autoimmune strain, and was not duplicated within lacrimal tissues of nonautoimmune BALB/c mice. The majority of immune-response genes regulated by testosterone were of the inflammatory type. Conclusions: Our findings support our hypothesis and indicate a major role for the lacrimal gland microenvironment in mediating androgen effects on immune gene expression.