Juvenile Sjogren's Syndrome (JSS) Transcriptome Study

Sjögren's disease (SjD) is a systemic autoimmune disorder with major clinical manifestations of dryness in the eyes and mouth, fatigue, and joint pain. Our interdisciplinary experts in SjD at the University of Florida newly discovered and established a cohort of SjD in children. Many of these patients with childhood SjD (cSjD) demonstrated a prominent feature of recurrent parotitis (RP). To understand the immunopathogenesis of childhood SjD (cSjD) for the first time in the field, we profiled the transcriptome of five groups of four PBMC samples by unbiased, high-throughput single-cell RNA sequencing (scRNA-seq): cSjD (n=4), non-cSjD (n=4), biopsy-positive non-cSjD (BP, n=4), biopsy-positive non-cSjD with RP (BPRP, n=4), and healthy controls (HC, n=4). In this study, RNA sequencing data, as well as all barcodes.tsv.gz, features.tsv.gz, and matrix.mtx.gz that may be used to create a Seurat object in R, will be availableTo protect the confidentiality of subjects, certain data were not assessed or collected in the subject phenotype dataset, such as race, age, height, weight, and education. ]]>
CASE and CONTROL: An approved IRB protocol is in place (#201900645) to recruit both male and female patients. De-identified specimens were collected from the subjects who visited the UF College of Dentistry and/or the UF Health Shands Hospital for their clinical care. Healthy children under 18 were not recruited as healthy controls since they do not normally visit the Pediatric Rheumatology Clinic. 1. PSS (Pediatric Sjögren's syndrome): 4 to 18 years old 2. Non-PSS: 4 to 18 years old. Mainly juvenile idiopathic arthritis (JIA) or those who fail to meet the SS criteria. 3. SS: 18-75 years old. Primary SS patients without other secondary autoimmune conditions. 4. Non-SS: 18 to 75 years old. Mainly rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or non-SS sicca patients who fail to meet the SS criteria. 5. HC: 18 to 75 years old. Mainly UF students and staff working at the UF Health Shands Hospital who do not exhibit signs and symptoms of autoimmune conditions and viral/bacterial infections. PSS and SS diagnoses were made based on the 2016 ACR/EULAR criteria for adult SS: 1) Patients with RA fulfill the 2010 ACR/EULAR criteria. 2) JIA (non-systemic) patients meet the international League of Association for Rheumatism (ILAR) criteria. 3) The 1997-updated criteria of the 1982-revised ACR criteria are used for SLE. 4) Non-SS-sicca patients include subjects with dry mouth and/or dry eye who did not fulfill the 2016 ACR/EULAR criteria. PSS or SS-associated recurrent parotitis was based on the history of symptoms and clinical presentation involving glandular swelling, pain, redness, and/or pus discharge, and confirmed with salivary gland ultrasound by Dr. Thatayatikom (rheumatologist and ultrasonographer). The possibility of bacterial or viral infection was evaluated by serology to rule out any primary and secondary infection as part of standard care. Characteristics FEMALE and MALE ADULT and PEDIATRIC patients: SS is a female dominant disease with over 90% being female patients. Therefore, most subjects recruited for this study were expected to be female adults. Pediatric patients with PSS at our institute show a female to male ratio of 7:3, which may change as our cohort grows in the future. INCLUSION CRITERIA: Cases will be PSS patients who have been newly diagnosed or established as PSS by a pediatric rheumatologist as long as they are free of immunosuppressive drugs within six months and anti-inflammatory meds within the last 24 hours, fulfilling the 2016 SS diagnostic criteria. PSS or SS patients treated with palliative methods and/or secretagogues to relieve dry mouth and dry eyes could be recruited for our study. EXCLUSION CRITERIA: We excluded subjects (cases or controls) with the following conditions: 1) autoimmune diseases and rheumatic diseases other than those listed above, 2) diabetes, 3) subjects treated with immunosuppressive agents, DMARDs, or biologics within six months and with anti-inflammatory meds within the last 24 hours, 4) subjects on xerogenic medications such as antidepressants, antibiotics, or anti-hypertensive drugs, or drugs that can cause lichenoid reactions, 5) current tobacco product users (smokers), 6) patients with salivary disease other than asymptomatic salivary enlargement, 7) patients that have ever had radiation to the head and neck, 8) history of organ transplant, 9) chemotherapy in the past 6 months, 10) contraindications to biopsy (e.g. liver or kidney failure), 11) immune diseases other than PSS or SS (e.g. HIV), and 12) acute viral/bacterial infection. ]]>

Sjögren's disease (SjD) 是一种全身性自身免疫性疾病，主要临床表现为眼干、口干、疲劳与关节疼痛。佛罗里达大学舍格伦综合征跨学科研究团队新近发现并建立了儿童舍格伦综合征（childhood SjD, cSjD）队列。此类儿童患者的显著特征之一为复发性腮腺炎（recurrent parotitis, RP）。为在该领域首次阐明儿童舍格伦综合征的免疫发病机制，我们采用无偏倚高通量单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）技术，对5组各4例外周血单个核细胞（peripheral blood mononuclear cell, PBMC）样本进行了转录组分析：儿童舍格伦综合征组（cSjD，n=4）、非儿童舍格伦综合征组（non-cSjD，n=4）、活检阳性非儿童舍格伦综合征组（biopsy-positive non-cSjD, BP，n=4）、伴复发性腮腺炎的活检阳性非儿童舍格伦综合征组（biopsy-positive non-cSjD with RP, BPRP，n=4）以及健康对照组（healthy controls, HC，n=4）。本研究的RNA测序数据，以及所有可用于在R语言中构建Seurat对象的barcodes.tsv.gz、features.tsv.gz与matrix.mtx.gz文件均将公开获取。为保护受试者隐私，受试者表型数据集中未采集或未评估种族、年龄、身高、体重与受教育程度等信息。

病例与对照：本研究已获得机构审查委员会（Institutional Review Board, IRB）批准（编号#201900645），拟招募男女受试者。脱标识样本采集自前往佛罗里达大学牙科学院（UF College of Dentistry）和/或佛罗里达大学健康尚兹医院（UF Health Shands Hospital）接受临床诊疗的受试者。由于18岁以下健康儿童通常不会就诊于儿科风湿病门诊，故未将其纳入健康对照组。
1. 儿童原发性舍格伦综合征（Pediatric Sjögren's syndrome, PSS）：年龄4~18岁；
2. 非PSS组：年龄4~18岁，主要为幼年特发性关节炎（juvenile idiopathic arthritis, JIA）患者或不符合舍格伦综合征诊断标准的受试者；
3. 成人原发性舍格伦综合征（SS）：年龄18~75岁，为无其他继发性自身免疫疾病的原发性舍格伦综合征患者；
4. 非SS组：年龄18~75岁，主要为类风湿关节炎（rheumatoid arthritis, RA）、系统性红斑狼疮（systemic lupus erythematosus, SLE）患者或不符合舍格伦综合征诊断标准的非舍格伦综合征干燥综合征患者；
5. 健康对照组（HC）：年龄18~75岁，主要为佛罗里达大学健康尚兹医院的教职工与学生，无自身免疫疾病、病毒或细菌感染的体征与症状。

儿童与成人原发性舍格伦综合征的诊断均依据2016年美国风湿病学会/欧洲抗风湿病联盟（ACR/EULAR）制定的成人舍格伦综合征诊断标准：1) 类风湿关节炎患者需符合2010年ACR/EULAR制定的诊断标准；2) 非全身性幼年特发性关节炎患者需符合国际风湿病学会联盟（International League of Associations for Rheumatism, ILAR）制定的诊断标准；3) 系统性红斑狼疮的诊断采用1982年修订并于1997年更新的ACR标准；4) 非舍格伦综合征干燥综合征患者指符合口干和/或眼干症状，但未达到2016年ACR/EULAR制定的舍格伦综合征诊断标准的受试者。

儿童或成人原发性舍格伦综合征相关复发性腮腺炎的诊断依据为：存在腺体肿胀、疼痛、红肿和/或流脓的症状与临床表现史，并经风湿病学兼超声医师Thatayatikom医生通过唾液腺超声检查确认。研究通过血清学检测评估细菌或病毒感染的可能性，以排除原发性与继发性感染，此为标准诊疗流程的组成部分。

受试者特征：舍格伦综合征为女性主导的疾病，女性患者占比超过90%，因此本研究招募的多数受试者预计为成年女性。本中心的儿童原发性舍格伦综合征患者男女比例为7:3，未来随着队列规模扩大，该比例或发生变化。

纳入标准：本研究的病例为经儿科风湿病医生新确诊或确诊为儿童原发性舍格伦综合征的患者，且需满足：近6个月内未使用免疫抑制药物，近24小时内未使用抗炎药物，且符合2016年ACR/EULAR制定的舍格伦综合征诊断标准。接受姑息治疗和/或使用促分泌剂缓解口干、眼干症状的儿童或成人原发性舍格伦综合征患者，均可纳入本研究。

排除标准：排除符合以下任意一种情况的受试者（病例或对照）：
1. 除上述所列疾病外的自身免疫性疾病与风湿性疾病；
2. 糖尿病；
3. 近6个月内使用过免疫抑制剂、改善病情抗风湿药（disease-modifying antirheumatic drugs, DMARDs）或生物制剂，且近24小时内使用过抗炎药物的受试者；
4. 正在使用致口干药物（如抗抑郁药、抗生素、抗高血压药）或可引起苔藓样反应的药物的受试者；
5. 当前吸烟者；
6. 除无症状唾液腺肿大外，存在其他唾液腺疾病的患者；
7. 曾接受头颈部放射治疗的患者；
8. 有器官移植史的患者；
9. 近6个月内接受过化疗的患者；
10. 存在活检禁忌证（如肝肾功能衰竭）的患者；
11. 除儿童或成人原发性舍格伦综合征外的其他免疫疾病（如HIV感染）患者；
12. 急性病毒或细菌感染患者。