Research on disease diagnosis based on teacher-student network and Raman spectroscopy.

Diabetic nephropathy is a serious complication of diabetes, and primary Sjögren's syndrome is a disease that poses a major threat to women's health. Therefore, studying these two diseases is of practical significance. In the field of spectral analysis, although common Raman spectral feature selection models can effectively extract features, they have the problem of changing the characteristics of the original data. The teacher-student network combined with Raman spectroscopy can perform feature selection while retaining the original features, and transfer the performance of the complex deep neural network structure to another lightweight network structure model. This study selects five flow learning models as the teacher network, builds a neural network as the student network, uses multi-layer perceptron for classification, and selects the optimal features based on the evaluation indicators accuracy, precision, recall, and F1-score. After five-fold cross-validation, the research results show that in the diagnosis of diabetic nephropathy, the optimal accuracy rate can reach 98.3%, which is 14.02% higher than the existing research; in the diagnosis of primary Sjögren's syndrome, the optimal accuracy rate can be reached 100%, which is 10.48% higher than the existing research. This study proved the feasibility of Raman spectroscopy combined with teacher-student network in the field of disease diagnosis by producing good experimental results in the diagnosis of diabetic nephropathy and primary Sjögren's syndrome.

[Primary nasopharyngeal carcinoma with Sjögren's syndrome and positive cerebrospinal fluid Epstein-Barr virus: a case report and literature review].

The study presents an analysis of the diagnostic and treatment protocol for a patient with a first episode of nasopharyngeal carcinoma who also has Sjogren's syndrome and Epstein-Barr Virus (EBV) positive cerebrospinal fluid, as detected through metagenomic next-generation sequencing (mNGS). It reviews existing literature to examine the connections between EBV and various conditions including Sjogren's syndrome, encephalitis or meningitis, and nasopharyngeal carcinoma, emphasizing the importance of EBV positive cerebrospinal fluid. The study focuses on a case from the Eighth Medical Center of the General Hospital of the People's Liberation Army, where a patient was admitted with headaches as the primary symptom on March 3, 2021. This patient had a history of Sjogren's syndrome and was later diagnosed with nasopharyngeal carcinoma. The research involved reviewing both domestic and international databases for cases related to cerebrospinal fluid EBV positive encephalitis or meningitis, and nasopharyngeal carcinoma. It aimed to aggregate data on demographics, initial symptoms, treatment methods, and patient outcomes. Findings suggest that positive cerebrospinal fluid EBV is linked to autoimmune diseases, viral encephalitis or meningitis, and nasopharyngeal carcinoma, albeit infrequently in the context of Sjogren's syndrome. Notably, EBV positive cerebrospinal fluid is commonly associated with recurrent nasopharyngeal carcinoma rather than initial episodes. The study concludes that for patients with an immune condition, exhibiting symptoms like headaches or cranial nerve issues, or in cases where nasopharyngeal carcinoma is suspected, early testing through cerebrospinal fluid mNGS or EBV DNA is recommended. This approach facilitates risk assessment, prognosis determination, and the creation of individualized treatment plans.

Raman hyperspectroscopy of saliva and machine learning for Sjögren's disease diagnostics.

Sjögren's disease is an autoimmune disorder affecting exocrine glands, causing dry eyes and mouth and other morbidities. Polypharmacy or a history of radiation to the head and neck can also lead to dry mouth. Sjogren's disease is often underdiagnosed due to its non-specific symptoms, limited awareness among healthcare professionals, and the complexity of diagnostic criteria, limiting the ability to provide therapy early. Current diagnostic methods suffer from limitations including the variation in individuals, the absence of a single diagnostic marker, and the low sensitivity and specificity, high cost, complexity, and invasiveness of current procedures. Here we utilized Raman hyperspectroscopy combined with machine learning to develop a novel screening test for Sjögren's disease. The method effectively distinguished Sjögren's disease patients from healthy controls and radiation patients. This technique shows potential for development of a single non-invasive, efficient, rapid, and inexpensive medical screening test for Sjögren's disease using a Raman hyper-spectral signature.

The diagnosis and misdiagnosis of Sjögren disease.

Although one of the most common systemic autoimmune disorders, Sjögren disease (SjD) may be overlooked in patients presenting with non-specific symptoms or no complaints of sicca symptoms. SjD is not a condition to be missed as patients could present with serious extra-glandular manifestations, including lymphomas. In this article, we discuss the diagnostic pitfalls of this disorder and encourage physicians to consider carefully the 'non-textbook' presentations.

Unusual presentation of Sjogren's syndrome during pregnancy: a case report.

BACKGROUND: Pregnancy imposes significant physiological changes, including alterations in electrolyte balance and renal function. This is especially important because certain disorders might worsen and make people more susceptible to electrolyte abnormalities. One such condition is Sjogren's syndrome (SS), an autoimmune disease that can cause distal renal tubular acidosis (dRTA). This case report offers a unique perspective on the intricate physiological interplay during pregnancy, emphasizing the critical importance of recognizing and managing electrolyte abnormalities, particularly in the context of autoimmune disorders such as Sjogren's syndrome. CASE PRESENTATION: We report a case of a 31-year-old pregnant Indian woman at 24 weeks gestation presenting with fever, gastrointestinal symptoms, and progressive quadriparesis followed by altered sensorium. Severe hypokalaemia and respiratory acidosis necessitated immediate intubation and ventilatory support. Investigations revealed hypokalaemia, normal anion gap metabolic acidosis, and positive autoimmune markers for SS. Concurrently, she tested positive for IgM Leptospira. Management involved aggressive correction of electrolyte imbalances and addressing the underlying SS and leptospirosis. CONCLUSION: This case underscores that prompt recognition and management are paramount to prevent life-threatening complications in pregnant patients with autoimmune disease. This report sheds light on the unique challenge of managing hypokalaemic quadriparesis in the context of Sjogren's syndrome during pregnancy.

Causal association between autoimmune liver disease and Sjögren's syndrome: A Mendelian randomization study.

BACKGROUND: Observational studies have found an association between autoimmune liver disease (AILD) and Sjögren's syndrome (SS). However, the causal relationship between the two remains unknown. Clinical guidelines indicate that the coexistence of AILD with other autoimmune diseases may impact prognosis and quality of life; hence, early recognition and management of extrahepatic autoimmune diseases is particularly crucial. Against this backdrop, this study aimed to utilize Mendelian randomization (MR) methods to investigate the potential causal relationship between AILD and SS. METHODS: We extracted summary statistics on AILD and SS from publicly available genome-wide association studies (GWAS) databases to identify appropriate instrumental variables (IVs). The inverse-variance weighted (IVW) method was utilized as the primary approach, with the weighted median (WM) method and MR-Egger method employed as supplementary methods to evaluate the potential causal relationship between the two conditions. Sensitivity analyses, including Cochran's Q test, MR-polynomial residuals and outliers (MR-PRESSO), MR-Egger intercept test, and the leave-one-out test, were performed to assess the stability of the results. RESULTS: The MR study results indicate a significant causal relationship between PBC and PSC with the risk of SS in the European population (IVW: odds ratio [OR] = 1.155, 95% confidence interval [CI]: 1.092-1.222, p < .001; IVW: OR = 1.162, 95% CI: 1.051-1.284, p = .003). A series of sensitivity analyses have confirmed the reliability of the results. CONCLUSIONS: Our study indicates that the presence of both PBC and PSC increases the susceptibility to SS. However, no reliable causal relationship was found between SS and the risk of PBC or PSC. These findings contribute to elucidating the potential pathogenic mechanisms of the disease and are of significant importance for the management of patients with PBC and PSC.

[Diffuse thickening of bronchial walls with multiple nodular mucosal protrusions].

A 58-year-old woman presented with a six-month history of nasal congestion, sore throat and cough, and a five-month history of dyspnea. She had a history of xerostomia for one year. On examination, the bilateral submandibular gland and parotid glands were enlarged. Parotid and anterior cervical lymph nodes were palpable. There were rales in both lungs. The rest of the physical examination was unremarkable. Sialographic analysis showed normal caliber in the main duct, stenosis in secondary ducts, and dilation in the proximal ducts. Minor salivary gland biopsy demonstrated periductal lymphocytic infiltration. Chest computed tomography (CT) showed diffuse thickening of the tracheal and bilateral bronchial walls. Bronchoscopy revealed macroscopic multiple nodules mainly in the trachea and bilateral main bronchus. Endobronchial biopsy showed lymphocytic infiltration in the bronchial submucosa. She was diagnosed with Sjögren's syndrome and treated with glucocorticoids. The dose of prednisone was started at 30 mg/d and tapered gradually. Following treatment, the patient's clinical condition improved dramatically, with shrinkage of the enlarged lymph nodes, bilateral submandibular and parotid glands. A repeated chest CT scan revealed improvement of the tracheal and bilateral bronchial thickening. Multiple nodules in the airway regressed, as evidenced by repeated bronchoscopic examination. The final diagnosis was a large-airway disease associated with Sjögren's syndrome.Among airway diseases in Sjögren's syndrome, peripheral airway diseases including bronchiolitis and bronchiectasis are common; however, central airway lesions in Sjögren's syndrome, especially with macroscopic nodules, are rare. In this case, we demonstrated tracheal and endobronchial nodules in Sjögren's syndrome as determined by clinical features, CT scan, bronchoscopy, and response to therapy.

Extranodal Rosai-Dorfman disease manifesting as Sjögren's syndrome combined with panuveitis and hypertrophic pachymeningitis: a case report and review of literature.

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by massive lymphadenopathy and systemic extranodal lesions. We present the case of a 28-year-old woman who presented with recurrent blurred vision in her right eye for 3 months. She developed blindness and atrophy in her left eye a decade prior to presentation. She subsequently developed headache, fever, and impaired mental status. Cranial magnetic resonance imaging indicated hypertrophic pachymeningitis (HP), and 18F-fluoro-2-deoxy-2-d-glucose (FDG) positron emission tomography/computed tomography revealed significant FDG uptake in the left dura mater. Autoimmune testing revealed elevated anti-nuclear, anti-SS-A, and anti-SS-B antibody levels. Incisional biopsy of the atrophic eyeball revealed RDD with marked polyclonal plasmacytosis. The patient was diagnosed with RDD accompanied by multisystem involvement, including Sjögren's syndrome (SS), panuveitis, and HP. Treatment with methylprednisolone for several weeks resulted in significant improvement. This is the first reported case of RDD presenting with SS in combination with panuveitis and HP. Although RDD is rarely diagnosed in young patients, interdisciplinary collaboration is essential to prevent a delayed diagnosis.

Distinctive profile of monomeric and polymeric anti-SSA/Ro52 immunoglobulin A1 isoforms in saliva of patients with primary Sjögren's syndrome and Sicca.

OBJECTIVE: Primary Sjögren's syndrome (pSS) is the second most common chronic autoimmune connective tissue disease. Autoantibodies, immunoglobulin (IgG) anti-SSA/Ro, in serum is a key diagnostic feature of pSS. Since pSS is a disease of the salivary gland, we investigated anti-SSA/Ro52 in saliva. METHODS: Using a novel electrochemical detection platform, Electric Field-Induced Release and Measurement, we measured IgG/M/A, IgG, IgA, IgA isotypes (IgA1 and IgA2) and IgA1 subclasses (polymeric and monomeric IgA1) to anti-SSA/Ro52 in saliva supernatant of 34 pSS, 35 dry eyes and dry mouth (patients with Sicca) and 41 health controls. RESULTS: Saliva IgG/M/A, IgG, IgA, IgA isotypes and IgA1 subclasses to anti-SSA/Ro52 differed significantly between pSS, non-pSS Sicca and healthy subjects. Elevated monomeric IgA1 was observed in patients with non-pSS Sicca while elevated polymeric IgA1 (pIgA1) was observed in patients with pSS. Salivary polymeric but not monomeric IgA1 (mIgA1) isoform correlated with focus score (r2=0.467, p=0.001) CONCLUSIONS: Salivary anti-Ro52 polymeric IgA1 isoform is associated with glandular inflammation in pSS, while salivary monomeric IgA1 is associated with Sicca. Whether IgA1 isotope switching plays a role in the progression of the Sicca to pSS warrants further investigation.

The Florida Scoring System for stratifying children with suspected Sjögren's disease: a cross-sectional machine learning study.

BACKGROUND: Childhood Sjögren's disease is a rare, underdiagnosed, and poorly-understood condition. By integrating machine learning models on a paediatric cohort in the USA, we aimed to develop a novel system (the Florida Scoring System) for stratifying symptomatic paediatric patients with suspected Sjögren's disease. METHODS: This cross-sectional study was done in symptomatic patients who visited the Department of Pediatric Rheumatology at the University of Florida, FL, USA. Eligible patients were younger than 18 years or had symptom onset before 18 years of age. Patients with confirmed diagnosis of another autoimmune condition or infection with a clear aetiological microorganism were excluded. Eligible patients underwent comprehensive examinations to rule out or diagnose childhood Sjögren's disease. We used latent class analysis with clinical and laboratory variables to detect heterogeneous patient classes. Machine learning models, including random forest, gradient-boosted decision tree, partial least square discriminatory analysis, least absolute shrinkage and selection operator-penalised ordinal regression, artificial neural network, and super learner were used to predict patient classes and rank the importance of variables. Causal graph learning selected key features to build the final Florida Scoring System. The predictors for all models were the clinical and laboratory variables and the outcome was the definition of patient classes. FINDINGS: Between Jan 16, 2018, and April 28, 2022, we screened 448 patients for inclusion. After excluding 205 patients due to symptom onset later than 18 years of age, we recruited 243 patients into our cohort. 26 patients were excluded because of confirmed diagnosis of a disorder other than Sjögren's disease, and 217 patients were included in the final analysis. Median age at diagnosis was 15 years (IQR 11-17). 155 (72%) of 216 patients were female and 61 (28%) were male, 167 (79%) of 212 were White, and 20 (9%) of 213 were Hispanic, Latino, or Spanish. The latent class analysis identified three distinct patient classes: class I (dryness dominant with positive tests, n=27), class II (high symptoms with negative tests, n=98), and class III (low symptoms with negative tests, n=92). Machine learning models accurately predicted patient class and ranked variable importance consistently. The causal graphical model discovered key features for constructing the Florida Scoring System. INTERPRETATION: The Florida Scoring System is a paediatrician-friendly tool that can be used to assist classification and long-term monitoring of suspected childhood Sjögren's disease. The resulting stratification has important implications for clinical management, trial design, and pathobiological research. We found a highly symptomatic patient group with negative serology and diagnostic profiles, which warrants clinical attention. We further revealed that salivary gland ultrasonography can be a non-invasive alternative to minor salivary gland biopsy in children. The Florida Scoring System requires validation in larger prospective paediatric cohorts. FUNDING: National Institute of Dental and Craniofacial Research, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Heart, Lung, and Blood Institute, and Sjögren's Foundation.

Seronegative patients with primary Sjögren's syndrome and non-pSS sicca test positive for anti-SSA/Ro52 and -Ro60 in saliva.

OBJECTIVES: Testing for anti-SSA/Ro antibodies in serum is essential in the diagnostic work-up for primary Sjögren's syndrome (pSS). In this study, we aimed to validate our previous assay for detection of salivary anti-SSA/Ro52, and to develop assays for detection of salivary anti-SSA/Ro60 and for detection of anti-Ro52 and -Ro60 in plasma using the electric field-induced release and measurement (EFIRM) platform. METHODS: Whole saliva samples from two independent Danish cohorts (DN1 and DN2) including 49 patients with pSS, 73 patients with sicca symptoms, but not fulfilling the classification criteria for pSS (non-pSS sicca), and 51 healthy controls (HC), as well as plasma samples from the DN1 cohort were analyzed using EFIRM to detect anti-SSA/Ro52 and -Ro60. RESULTS: In the DN1 cohort, 100 % in the pSS group and 16 % in the non-pSS sicca group were serum anti-SSA/Ro positive by ELISA. EFIRM detected anti-SSA (Ro52 and/or -Ro60) in plasma and saliva in 100 % and 96 % patients with pSS, and 16 % and 29 % with non-pSS sicca. In the DN2 cohort, 80 % patients with pSS and 26 % with non-pSS sicca were serum anti-SSA/Ro positive. Salivary anti-SSA discriminated patients with pSS from HC and non-pSS sicca with an AUC range of 0.74-0.96 in the DN1 and DN2 cohorts. EFIRM discriminated pSS from non-pSS sicca with an AUC of 0.98 in plasma. CONCLUSION: Our findings suggest that salivary anti-SSA/Ro antibodies are potential discriminatory biomarkers for pSS, which may also identify seronegative patients, addressing the unmet clinical need of early detection and stratification of pSS.

KLRB1 defines an activated phenotype of CD4+ T cells and shows significant upregulation in patients with primary Sjögren's syndrome.

OBJECTIVE: This study aimed to investigate the role of KLRB1 (CD161) in human CD4+ T cells and elucidate its significance in primary Sjögren's syndrome (pSS). METHODS: Peripheral blood samples from 37 healthy controls and 44 pSS patients were collected. The publicly available single-cell RNA-Seq data from pSS patient PBMCs were utilized to analyse KLRB1 expression in T cells. KLRB1-expressing T lymphocyte subset proportions in pSS patients and healthy controls were determined by flow cytometry. CD25, Ki-67, cytokine secretion, and chemokine receptor expression in CD4+ KLRB1+ T cells were detected and compared with those in CD4+ KLRB1- T cells. Correlation analysis was conducted between KLRB1-related T-cell subsets and clinical indicators. ROC curves were generated to explore the diagnostic potential of KLRB1 for pSS. RESULTS: KLRB1 was significantly upregulated following T-cell activation, and Ki-67 and CD25 expression was significantly greater in CD4+ KLRB1+ T cells than in CD4+ KLRB1- T cells. KLRB1+ CD4+ T cells exhibited greater IL-17A, IL-21, IL-22, and IFN-γ secretion upon stimulation, and there were significantly greater proportions of CCR5+, CCR2+, CX3CR1+, CCR6+, and CXCR3+ cells among CD4+ KLRB1+ T cells than among CD4+ KLRB1- T cells. Compared with that in HCs, KLRB1 expression in CD4+ T cells was markedly elevated in pSS patients and significantly correlated with clinical disease indicators. CONCLUSION: KLRB1 is a characteristic molecule of the CD4+ T-cell activation phenotype. The increased expression of KLRB1 in the CD4+ T cells of pSS patients suggests its potential involvement in the pathogenesis of pSS and its utility as an auxiliary diagnostic marker for pSS.

Primary Sjögren's syndrome independently promotes premature subclinical atherosclerosis.

OBJECTIVES: Cardiovascular comorbidities are common in patients with autoimmune diseases. This study investigates the extent of subclinical atherosclerosis in patients with primary Sjögren's syndrome (pSS). Correlations with clinical factors such as organ involvement (OI) or disease activity were analysed and oxLDL antibodies (oxLDL ab) were measured as potential biomarkers of vascular damage. METHODS: Patients with pSS were consecutively included from the rheumatology outpatient clinic. Age- and sex-matched controls were recruited (2:1 ratio). Data collection was performed by a standardised questionnaire and Doppler ultrasound to evaluate the plaque extent and carotid intima-media thickness (cIMT). Propensity score matching included all cardiovascular risk (CVR) factors and corresponding laboratory markers. RESULTS: Data were available for 299 participants (199 pSS/100 controls), aged 59.4 years (50.6-65.0), 19.1% male. After matching, the pSS cohort had greater cIMT (p<0.001) and plaque extent (OR=1.82; 95% CI 1.14 to 2.95). Subgroup analyses of patients with pSS revealed that OI was associated with increased cIMT (p=0.025) and increased plaque occurrence compared with patients without OI (OR=1.74; 95% CI 1.02 to 3.01). OxLDL ab tended to be lower in patients with plaque (p=0.052). Correlations of higher Oxidized Low Density Lipoprotein (oxLDL) ab with EULAR Sjögren's Syndrome Disease Activity Index (p<0.001) and anti-Sjögren's-syndrome-related antigen A autoantibodies (SSA/Ro antibodies) (p=0.026) were observed. CONCLUSIONS: Subclinical atherosclerosis occurs earlier and more severely in patients with pSS. The difference in cIMT between pSS and controls seems mainly driven by patients with OI, suggesting that this subgroup is particularly at risk. OxLDL ab might protect against atherosclerotic progression in patients with pSS. CVR stratification and preventive medications such as Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors should be discussed and further longitudinal studies are needed.

A relatively rare traditional Chinese medicine pattern of primary Sjögren syndrome: A case report.

RATIONALE: This report presents a unique case of a patient diagnosed with Primary Sjögren's syndrome and a relatively rare traditional Chinese medicine pattern, known as the combined cold and heat pattern and cold-dampness syndrome. The patient's condition was successfully managed using Chinese herbal medicine, specifically the modified Da-Chai-Hu decoction and Linggui Zhugan decoction. PATIENT CONCERNS: A 56-year-old woman had chronic dry eye and mouth for over 10 years. She was initially managed with traditional Chinese herbal medicine (TCHM) prescriptions, including the Zengye decoction, but the therapeutic effects were unsatisfactory. As the disease progressed, she was diagnosed with an anxiety disorder due to symptoms of vexation and insomnia. Treatment with alprazolam and venlafaxine failed to alleviate these symptoms. Recently, her general condition gradually worsened, with symptoms including a bitter taste in her mouth, dizziness, hot flashes, chills, poor appetite, chest discomfort, and constipation. DIAGNOSES: After a series of examinations, including a Schirmer test and labial gland biopsy, she was diagnosed with Sjögren's syndrome. INTERVENTIONS: Despite regular treatment with pilocarpine, sodium hyaluronate eye drops, venlafaxine, and alprazolam, the dry mouth symptoms intensified. Consequently, she sought further intervention through the TCHM. OUTCOMES: After 8 weeks of treatment with the modified Da-Chai-Hu decoction and Linggui Zhugan decoction, she reported a significant improvement in her dryness-related symptoms and sleep quality. LESSONS: This case report demonstrates that TCHM can effectively treat Primary Sjögren's syndrome, and should be considered for broader applications. Furthermore, this underscores the importance of tailoring treatment formulas to patients by identifying their specific syndrome differentiation in a clinical setting.

Clinical Performance of Immunonephelometric Assay and Chemiluminescent Immunoassay for Detection of IgG Subclasses in Chinese.

BACKGROUND: Detection of IgG subclasses (IgGSc) is vital for the diagnosis and management of disease, especially IgG4-related diseases (IgG4-RD). This study aimed to evaluate the performances of the chemiluminescent immunoassay (CLIA) for detecting IgGSc and diagnosing IgG4-RD by IgGSc. METHODS: A total of 40 individuals with IgG4-RD, 40 with primary Sjogren's syndrome (pSS), and 40 healthy controls (HCs) were enrolled. Serum samples were collected for the simultaneous detection of IgG1, IgG2, IgG3, and IgG4 by the Siemens immunonephelometric assay and the CLIA. The correlation analysis was performed, and diagnostic value was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: Patients with IgG4-RD had higher IgG4 (p < 0.001) and lower IgG1 (p < 0.001) than those with pSS, and HC. The results by the Siemens immunonephelometric assay and the CLIA showed a strong correlation in detecting IgG1, IgG2, IgG3, and IgG4 (r = 0.937, r = 0.847, r = 0.871, r = 0.990, all p < 0.001, respectively). The sum of IgG1, IgG2, IgG3, and IgG4 using two assays strongly correlated with total IgG by the IMMAGE 800 (r = 0.866, r = 0.811, both p < 0.001, respectively). For discriminating IgG4-RD from pSS and HC, no significant differences were observed in CLIA IgG4 and Siemens immunonephelometric assay IgG4 (z = 0.138, p = 0.891), which provided the area under the curves (AUCs) of 0.951 (p < 0.001) and 0.950 (p < 0.001), respectively. The AUCs of CLIA IgG1 and Siemens immunonephelometric assay IgG1 in distinguishing pSS from IgG4-RD and HC were 0.761 (p < 0.001) and 0.765 (p < 0.001), respectively, with no significant differences (z = 0.228, p = 0.820). CONCLUSIONS: The CLIA and the Siemens immunonephelometric assay appeared to have good consistency with comparable diagnostic value in detecting IgGSc, especially IgG4, and IgG1 that can accurately identify IgG4-RD or pSS in clinical practice.

Single-cell transcriptomics unveil profiles and interplay of immune subsets in rare autoimmune childhood Sjögren's disease.

Childhood Sjögren's disease represents critically unmet medical needs due to a complete lack of immunological and molecular characterizations. This study presents key immune cell subsets and their interactions in the periphery in childhood Sjögren's disease. Here we show that single-cell RNA sequencing identifies the subsets of IFN gene-enriched monocytes, CD4+ T effector memory, and XCL1+ NK cells as potential key players in childhood Sjögren's disease, and especially in those with recurrent parotitis, which is the chief symptom prompting clinical visits from young children. A unique cluster of monocytes with type I and II IFN-related genes is identified in childhood Sjögren's disease, compared to the age-matched control. In vitro regulatory T cell functional assay demonstrates intact functionality in childhood Sjögren's disease in contrast to reduced suppression in adult Sjögren's disease. Mapping this transcriptomic landscape and interplay of immune cell subsets will expedite the understanding of childhood Sjögren's disease pathogenesis and set the foundation for precision medicine.