Sjögren's Syndrome Research Articles

Association Between Quantitative Sialoscintigraphy and Antibody Profiles in Patients With Sjögren or Sicca Syndrome.

This study analyzed the association between anti-Ro/SSA and anti-La/SSB antibody levels with quantitative and visual sialoscintigraphy patterns in patients suspected of having Sjögren or sicca syndrome. Medical records of patients who underwent sialoscintigraphy between April 2020 and May 2022 were reviewed. Associations between antibody levels and sialoscintigraphy parameters were evaluated using linear regression. Receiver operating characteristic curve analysis was used to identify antibody cutoff values for predicting flat-type patterns and the risk of Sjögren or sicca syndrome. Of the 170 patients (mean age, 56.6 years; 78.8% female), 95.3% had dry mouth and eyes, 30% experienced polyarthralgia, and 66.5% were prescribed hydroxychloroquine. The most common sialoscintigraphy finding was the median-type time-activity curve (TAC) pattern. Anti-Ro/SSA and anti-La/SSB levels were significantly correlated with maximum accumulation or maximum secretion in the salivary glands. Receiver operating characteristic analysis for anti-Ro/SSA predicting a flat-type TAC pattern showed an area under the curve (AUC) of 0.659 to 0.780, with specificity between 82.1% and 86.3% for antibody levels greater than 85.2 units. Anti-Ro/SSA levels greater than 49.75 units predicted a higher risk of Sjögren or sicca syndrome, with an AUC of 0.622 and 83.9% specificity. Anti-La/SSB levels had no significant predictive value, with an AUC of 0.554. Anti-Ro/SSA levels greater than 85.2 units were strong predictors of flat-type TAC patterns, indicating near-total salivary gland dysfunction and supporting their diagnostic utility in Sjögren or sicca syndrome.

Decreased prevalence and altered clinical phenotype of systemic sclerosis and other autoimmune connective tissue diseases in type 1 and type 2 diabetes: A cross-sectional observational study.

Evidence has demonstrated that autoimmune diseases tend to coexist at a higher rate than expected, reflecting a common pathogenic pathway. In this study, we investigate the co-occurrence of systemic sclerosis, systemic lupus erythematosus, and Sjogren syndrome in patients with type 1 and type 2 diabetes mellitus. Our data were obtained using the 2019 Healthcare Cost and Utilization Project, and International Classification of Diseases, 10th Revision diagnosis codes were used to identify patients with systemic sclerosis, systemic lupus erythematosus, lupus nephritis, and Sjogren syndrome, as well as patients with type 1 and type 2 diabetes. We utilized Statistical Analysis System 9.4 for all analyses and included designated weight values to produce nationally representative estimates. The prevalence of systemic sclerosis among patients with type 1 diabetes mellitus and type 2 diabetes mellitus was significantly lower than that for the non-diabetes mellitus control group (0.0007% vs 0.09%, p-value = 0.0064 and 0.01% vs 0.07%, p-value < 0.0001), respectively. Similarly, there was a significant decrease in the prevalence of systemic sclerosis with lung involvement in patients with type 1 and type 2 diabetes mellitus, with a statically significant difference in type 2 diabetes mellitus versus nondiabetic group (0.001% vs 0.006%, p-value < 0.0001). We noted a similar pattern regarding the prevalence of systemic lupus erythematosus and lupus nephritis in patients with type 1 and 2 diabetes. Similarly, there was a significant decrease in the prevalence of Sjogren syndrome in patients with type 1 diabetes and type 2 diabetes. The collected data demonstrates an inverse relation between some autoimmune connective tissue diseases and diabetes. This suggests that these diseases and diabetes mellitus may have different immune pathogenesis. There was also a significantly lower incidence of organ complications such as lupus nephritis and systemic sclerosis lung disease among patients with diabetes, suggesting that diabetes and treatment of diabetes may alter the clinical expression of these disorders.

Functional assessment of major salivary glands using scintigraphy

To demonstrate a methodology of scintigraphy imaging interpretation considering pixel intensity values in groups of patients presenting lupus erythematosus, Sjögren’s Syndrome (SS), SS associated to systemic lupus erythematosus, parotiditis, drug-induced sialorrhea and salivary glands disease-free. Material and methods: A total of 36 salivary gland scintigraphy images that were from patients with lupus erythematosus, SS, SS combined lupus, parotiditis, and drug-induced sialorrhea were assessed. The pixel intensity of the scintigrams was also evaluated using the standardized grayscale at 8 bits, Images were analyzed under a region of interest (ROI) of 2 cm2 at maximum uptake using ImageJ. Results: Significant differences between the groups were obtained both for parotid (p=0.026) and submandibular glands (p=0.0952). Statistical significant differences were observed in post-hoc tests between Lupus combined with SS patients, for parotid and submandibular glands, when compared to normal group (p=0.04 and p=0.03 respectively). Pixel values were higher for Lupus combined with SS patients, representing a lower uptake. Conclusion: The pixel intensity assessment was able to differentiate and point to lower salivary flow rates for the systemic lupus erythematosus combined with SS patients when compared to other disorders affecting the salivary gland function.

Establishment of human minor salivary gland organoids in laminin-GelMA hydrogel from healthy individuals and Sjögren’s disease patients

Biopsies of human minor salivary glands (hMSGs), located beneath the oral mucosa, are crucial for a definitive clinical diagnosis of Sjögren’s Disease (SjD)。Although organoids from various exocrine glands have been cultured, organoids comprising the diverse cell types of hMSGs have not yet been successful. In this study, we established long-term cultures of hMSGs organoids derived from both healthy individuals and patients with SjD. The organoids, cultured in artificial laminin-GelMA hydrogel, retain distinct phenotypic and functional characteristics of the native glands, both when stimulated with neurotransmitters in vitro and upon transplantation in vivo. Single-cell RNA sequencing revealed that organoids from healthy individuals and from SjD patients exhibit unique phenotypic differences. Furthermore, treatment with tofacitinib enhanced the proliferation of patient organoids by inhibiting the JAK-STAT pathway, suggesting a potential therapeutic strategy for further investigation. Here, we derived organoids from healthy individuals as potential transplant material in regeneration medicine, and developed SjD hMSG organoids for use as a disease model for exploring SjD pathogenesis and developing therapeutic strategies.

Autoimmune dysphagia.

Dysphagia is a complication of several autoimmune rheumatic diseases and otorhinolaryngologists are likely to be involved in the assessment and management of patients with such conditions. This review provides an update on rheumatic diseases that may cause swallowing impairment, with particular focus on the epidemiology, pathophysiology and management of dysphagia in these conditions. Dysphagia is a common complication of the following rheumatic diseases: idiopathic inflammatory myopathies, systemic sclerosis, Sjogren's syndrome, systemic lupus erythematosus and rheumatoid arthritis. It may also be a complication of rarer autoimmune conditions such as Bechet's syndrome, sarcoidosis and granulomatosis with polyangiitis. All three stages of swallowing (oral, pharyngeal and oesophageal) may be impaired in these conditions. Both medical therapy and surgical intervention play an important role in the management of autoimmune dysphagia. The investigation and management of autoimmune dysphagia requires close collaboration between rheumatologists and otorhinolaryngologists. There is a need for further research to establish standardised guidelines on the assessment and management of autoimmune dysphagia.

Impact of risk factors for oral candidiasis in patients with Sjögren's syndrome

Background: Sjogren's Syndrome (SS) is an autoimmune disease in which the body attacks the exocrine glands. The characteristics of this syndrome involve dysfunction and destruction of the exocrine glands, leading to oral manifestations. Patients with Sjogren's Syndrome are at a significantly higher risk of developing oral cavity diseases. Common oral manifestations found in Sjogren's Syndrome include sialadenitis, lichen planus, and salivary swelling. Material and Methods: The literature review was carried out in Pubmed, ScienceDirect, and Researchgate as well as various relevant sources with the keywords: “Oral Candidiasis", “Sjogren’s Syndrome", "Oral Cavity Lesions”, "Flow Saliva", and "Oral Health." Conclusion: In patients with Sjogren's Syndrome, the saliva flow tends to decrease, which can increase the risk of higher levels of Candida albicans bacteria, thereby raising the likelihood of developing Oral Candidiasis.

Therapeutic potential of interleukin-17 neutralization in a novel humanized mouse model of Sjögren’s disease

Sjögren’s disease (SjD) is a chronic autoimmune disease, in which the immune system targets exocrine glands and leads to dryness symptoms. There is an increasing need to develop novel therapeutic approach as the treatment plan has not been changed in the past decade. However, findings in mouse model may not be directly applied in patients, given the substantial differences of immune system between human and mice. In the present study, using antigens derived from human salivary A-253 cells, we established experimental Sjögren’s syndrome (ESS) in mice with human immune system (HIS). HIS-ESS mice exhibited key features of human disease, including salivary hypofunction, increased serum levels of autoantibodies and tissue destruction in the salivary glands. Phenotypic analysis revealed enhanced effector B and T cell subsets, including Th1, Th17 and T follicular helper (Tfh) cells in HIS-ESS mice, while multiplex imaging analysis suggested enlarged B cell follicles and expanded memory B cells. IL-17 neutralization therapy significantly ameliorated disease pathology at both acute and chronic stages, in which B cells were mainly affected, to the less extent Th1 and Tfh cells in HIS-ESS mice. Together, HIS-ESS mouse model highly recapitulated SjD features and immunopathogenesis, which may serve as a useful tool in drug screening and pre-clinical studies.

Network meta-analysis of integrated traditional Chinese and Western medicine in the treatment of Sjogren’s syndrome

ObjectiveTo evaluate efficacy and safety of traditional Chinese medicine (TCM) combined with Western medicine in treatment of Sjogren’s syndrome (SS).MethodsCNKI, WanFang, VIP, CBM, Sinomed, PubMed, Embase, and Web of Science were searched to collect randomized controlled trials (RCTs) of TCM combined with conventional western medicine (CWM) in treating SS from the time of their estalishment to May 2023. The researchers independently screened the literature and extracted data for quality evaluation. Analyses were performed using Review Manager (version 5.4) and R-4.3.1.ResultsA total of 66 RCTs were included, with a sample size of 5,052, involving four kinds of TCM (total glucosides of paeony capsules, tripterygium glycosides tablet, Xinfeng capsule and Jinju Qingrun capsule) and three kinds of CWM(hydroxychloroquine sulfate, Iguratimod and glucocorticoid). The network meta-analysis results showed that IGU + HCQ + TGP ranked the highest in reducing ESR and IgG and improving the Schirmer test when the three drugs were combined. When the two drugs are combined, IGU + GC and TGT + TGP are good choices for reducing erythrocyte sedimentation rate (ESR) and Immunoglobulin G (IgG). Although TGP + HCQ vs. HCQ had the most studies, TGP combined with HCQ did not rank high in each outcome indicator. It is recommended to use TGT and XFG in decreasing ESR and IgG for a single drug. JJQR have an advantageous role in relieving xerostomia and dry eyes.ConclusionTCM combined with CWM has a very significant effect on treating SS compared with CWM alone. According to the network meta-analysis, the best intervention measures of different TCMs for different outcome indicators were obtained.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42023451845].

HIPK3 hypomethylation as a potential epigenetic biomarker in rheumatic immune diseases with emphasis on rheumatoid arthritis.

This study aimed to explore the potential of HIPK3 DNA methylation as a biomarker for rheumatoid arthritis (RA) by examining its methylation levels in various rheumatic immune diseases and analyzing its correlation with clinical indicators. We recruited 368 participants, including patients with RA, ankylosing spondylitis (AS), GOUT, psoriatic arthritis (PSA), sjogren's syndrome (SS), systemic lupus erythematosus (SLE), dermatomyositis (DM), and healthy controls (HC), and MethylTargetTM targeted region methylation sequencing technology was employed to analyze the DNA methylation levels of HIPK3 (cg15692052). We analyzed the HIPK3 methylation levels and correlated them with common clinical indicators. Transcriptome data from the GEO dataset (GSE93272) were also analyzed to assess HIPK3 mRNA expression levels in RA patients. Statistical analyses included Spearman correlation, One-Way ANOVA, Kruskal-Wallis tests, and ROC curve analysis. HIPK3 methylation levels were significantly lower in the RA, SLE, and DM groups compared to the HC group (P < 0.05). RA subgroups based on RF and CCP statuses also showed lower HIPK3 methylation levels compared to the HC group (P < 0.05). Analysis of the GEO dataset revealed significantly elevated HIPK3 mRNA expression in RA patients (P < 0.05). A negative correlation was found between HIPK3 methylation levels and ESR (r = -0.14, P = 7.1e-3), CRP (r = -0.25, P = 4.1e-7), RF (r = -0.18, P = 5.2e-4), and DAS28-CRP (r = -0.12, P = 0.04) in the RA group. ROC analysis indicated that HIPK3 methylation levels had high diagnostic value for RA (AUC = 0.742), SLE (AUC = 0.701), and DM (AUC = 0.948), especially in distinguishing seronegative RA (AUC = 0.612, 0.747, 0.836) and differentiating RA from AS (AUC = 0.788). The study suggests that HIPK3 hypomethylation in peripheral blood is associated with RA and correlated with inflammatory markers, such as CRP. HIPK3 methylation levels have potential as a novel biomarker for RA diagnosis and predicting inflammation trends, showing particular promise in differentiating RA from other types of arthritis. Key Points • MethylTargetTM targeted region methylation sequencing technology was employed to analyze the DNA methylation levels of HIPK3 (cg15692052). • HIPK3 methylation levels have potential as a novel biomarker for RA diagnosis and predicting inflammation trends.

Clinical characteristics and results of patients who underwent minor salivary gland biopsy with the suspicion of Sjogren syndrome

Objective: To evaluate the value and accuracy of biopsy in diagnosing Sjogren syndrome (SS) by evaluating the results of patients who underwent mınor salivary gland biopsy (MSGB) with the suspicion of SS. Material and Methods: The study was planned with a retrospective assessment of 127 patients with a biopsy performed for SS diagnosis. The clinical and laboratory characteristics of the patients who underwent MSGB were recorded from their files. SS diagnosis was placed using the rating system according to 2016 ACR/EULAR classification criteria or based on expert opinion. Results: 113 patients met the ınclusion criteria. 72 patients diagnosed with SS. 56 were diagnosed according to the 2016 ACR/EULAR classification criteria and 16 were diagnosed according to expert opinion. There were 57 patients with positive MSGB outcomes (55 SS, 2 not SS). There were 56 patients with MSGB negative outcomes (17 SS, 39 not SS). The sensitivity of MSGB for SS diagnosis was 76.4%, and the specificity was 95.1%. Conclusion: All of our patients had antibody test results, but the number of objective tests included in the classification criteria such as salivary flow rate and Schirmer was low. Although MSGB is considered an invasive technique, it appears to be safe technique as long as it is performed by experienced professionals. It will assist in the final decision for patients with SS suspicion and who cannot undergo other objective tests.

Headaches in Sjogren's disease: A narrative review.

To review the most common types of primary and secondary headaches that are associated with Sjogren's disease (SjD). Sjogren's disease is a chronic systemic autoimmune disease that typically presents with xerophthalmia, xerostomia, and arthralgias. Sensory and motor neuropathies are commonly reported neurological complications with SjD. Primary and secondary headaches are also frequent neurological complications associated with SjD, which may be under-recognized. In this study, researchers conducted a literature review through the platforms of PubMed and Google Scholar with the keywords: (1) Sjogren's syndrome, (2) Sjogren's disease, (3) headache, (4) migraine, (5) tension-type headache, (6) aseptic meningitis, (7) cerebral venous sinus thrombosis, and (8) idiopathic intracranial hypertension. Included articles involved a study population of patients with both SjD and headache. There were no exclusion criteria. A total of 54 articles were identified, and 31 articles were utilized for study analysis. In patients with SjD, headaches were a frequently reported neurological complaint. The most common types of primary headaches associated with SjD were found to be migraine and tension-type headache. Patients with SjD were more likely to report severe, debilitating headaches compared to the general population. Furthermore, patients with SjD have been found to experience dangerous types of secondary headaches, including aseptic meningitis and cerebral venous sinus thrombosis. Headaches are a common neurological complication in patients with SjD. Current literature suggests that there is an increased risk of both primary and secondary headaches in individuals with SjD compared to the general population and that headaches may occur throughout the clinical course of the disease. There are also reports of patients who experience the onset of primary and secondary headaches prior to the diagnosis of SjD. SjD has been linked to dangerous, life-threatening conditions that cause headaches, which require urgent recognition and treatment. Therefore, it is important to have a higher index of suspicion for patients who present with headaches and clinical symptoms of SjD, such as xerophthalmia and xerostomia. Utilizing a detailed history, physical examination, and neuroimaging can assist clinicians to recognize and diagnose types of headaches in patients with SjD to prevent dangerous complications.

A rare case of late-onset spondyloenchondrodysplasia with immune dysregulation presenting as adult-onset monogenic lupus.

Spondyloenchondrodysplasia is classified as an interferonopathy resulting from recessive mutations in the ACP5 gene and manifests with various clinical features, including distinctive skeletal dysplasia, neurological abnormalities, immune dysfunction resembling systemic lupus erythematosus (SLE) and Sjogren's syndrome. While SLE is typically considered multifactorial and more prevalent in adulthood, a subset of approximately 10%-25% of childhood cases arise from monogenic form. Among these, spondyloenchondrodysplasia accounts for only a rare fraction of monogenic lupus cases, with only 22 reported instances in the literature. This paper presents a new case of spondyloenchondrodysplasia-immune dysregulation (SPENCDI) in an adult patient born to nonconsanguineous parents. The patient was diagnosed with SPENCDI and exhibited immune neutropenia, anti-dsDNA positivity, platyspondyly, immune deficiency, and a homozygous variant (c.155A > C, p. Lys52Thr) in the ACP5 gene, previously classified as pathogenic. Notably, the patient achieved successful clinical management through the initiation of baricitinib treatment, a Janus kinase inhibitor. SPENCDI represents an uncommon cause of SLE in adulthood. Clinicians should be vigilant of underlying Mendelian inheritance when encountering patients with associated features. While treatments for both Mendelian and non-Mendelian SLE are similar, Janus kinase inhibitors like baricitinib show potential for managing interferon-signature monogenic SLE cases.

Sjögren's Disease and Gastroesophageal Reflux Disease: What Is Their Evidence-Based Link?

Sjögren's disease (SjD), or primary Sjögren's syndrome (pSS), is a heterogeneous chronic autoimmune disorder with multiple clinical manifestations that can develop into non-Hodgkin's lymphoma in mucosa-associated lymphoid tissue. SjD is one of the autoimmune diseases with the maximum delayed diagnosis due to its insidious onset, heterogeneous clinical features and varied course. It is increasingly recognized that extraglandular manifestations represent a clinical challenge for patients with SjD. The European League Against Rheumatism (EULAR) Sjögren's Syndrome (SS) Disease Activity Index (ESSDAI) is a systemic disease activity index designed to measure disease activity in patients with primary Sjogren's syndrome. It consists of 12 domains: cutaneous, pulmonary, renal, articular, muscular, peripheral nervous system, central nervous system, hematological, glandular, constitutional, lymphadenopathy and lymphoma, biological. More than a quarter of patients with pSS may have systemic features that are not included in the ESSDAI classification, i.e., various cardiovascular, ophthalmic, ENT, and other systemic or organ involvement that increase the magnitude of the systemic phenotype in the disease. The ESSDAI also excludes the gastrointestinal (GI) tract, and unfortunately, GI manifestations are not routinely assessed. Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal disorders, impairing quality of life and consuming a large volume of medical resources. Recently carried out the Mendelian randomized trial confirmed the causal link between SjD and gastroesophageal reflux disease (GERD) and showed that GERD is a risk factor for SjD. This review aims to provide an overview of the research describing evidenced based links between Sjögren's disease and gastroesophageal reflux disease, with the intention of ensuring that any systemic pathology in Sjögren's disease is properly assessed and that management of the disease is directed towards the patient. A comprehensive literature search was carried out on PubMed, Web of Science, Scopus and the Cochrane Library databases. Two researchers searched for published studies indexed from inception to 1 September 2024 using the keywords 'Sjögren's syndrome' OR 'Sjögren's disease' AND 'gastroesophageal reflux disease' AND 'microbiota' OR microbiota dysbiosis'. We limited our search for scientific articles to human studies, and only included articles in English. Overall, there is a lack of evidence-based studies assessing the association between GERD and Sjögren's disease and the changes in the microbiota associated with GERD in a multidisciplinary setting. Such studies are needed for the future, as this will improve the early diagnosis of Sjögren's disease and the personalized management of the disease.

Safety and Efficacy of Ianalumab in Patients With Sjögren's Disease: 52-Week Results From a Randomized, Placebo-Controlled, Phase 2b Dose-Ranging Study.

To report 52-week safety and efficacy of ianalumab from phase 2b dose-finding study in patients with Sjögren's disease (SjD). Patients randomly received (1:1:1:1) ianalumab (5, 50, or 300 mg) or placebo subcutaneously every 4 weeks till week 24 (treatment period [TP]1). At week 24, patients on 300 mg were re-randomized to continue 300 mg or receive placebo till week 52 (TP2), patients on placebo were switched to ianalumab 150 mg, while patients on 5 and 50 mg directly entered post treatment safety follow-up. Patients who discontinued treatment early or completed treatment entered safety follow-up (≥20 weeks). During TP1, 190 patients were randomized (placebo=49, 5 mg=47, 50 mg=47, 300 mg=47). Of these 190 patients, 90 (47.4 %; 43 continued 300 mg and 47 received placebo) entered TP2, and 81/90 (90.0%) completed the study treatment. By week 52, efficacy was sustained in patients who continued 300 mg in TP2 (ESSDAI, ESSPRI, PaGA, PhGA change from week 24: -1.45, -0.46, -4.69, -6.86, respectively). Stimulated salivary flow rates and autoantibody levels numerically improved in the 300 mg group. Treatment-emergent adverse events were not dose-dependent, except for injection-site reactions. Cases of decreased neutrophil counts (CTCAE v4.03 grade 3 according to laboratory listings) were observed in 3 patients during the post-treatment follow-up, occurring at 3.5, 5.5, and 3 months, after the last ianalumab administration. None were associated with infection except one incidental finding of asymptomatic cytomegalovirus infection (IgM+). In patients with SjD, ianalumab 300 mg demonstrated sustained efficacy through week 52 and a favorable safety profile up to two years of follow-up.

The Relationship Between Systemic Immune Inflammatory Level and Dry Eye in Patients with Sjögren's Syndrome.

Background and objectives: Sjögren Syndrome (SS) is a chronic, systemic, and progressive autoimmune disease in which inflammatory processes play a role. Dry eyes or mouth are present in approximately 95-98% of patients with pSS. This study aimed to evaluate the relationship between SII level and disease activity as well as dry eye involvement in patients with pSS. Materials and methods: A cross-sectional design was employed, and a total of 28 female patients who were aged 18-65 years and were diagnosed with pSS were involved. The Sjögren Syndrome Disease Activity Index (ESSDAI) was calculated in patients. The Schirmer test was applied to all patients. The relationship between SII level and disease activity as well as dry eye involvement in pSS patients was evaluated. Results: In our study, a strong positive correlation was found between the SII value and pSS disease activity, while a negative correlation was found between the Schirmer test, which shows dry eye findings, and eye drying time, and a positive correlation was found with the OSDI. Conclusions: this study reported a correlation between hematological parameters and the development of dry eye in pSS. NLR, PLR, and SII showed statistically significant changes in pSS patients.

The Impact of IgG Fc-Glycosylation on Disease Dynamics in Primary Sjögren's Disease- Insights from the Belgian Sjögren's Syndrome Transition Trial.

Glycans attached to the fragment crystallizable region (Fc) of IgG antibodies influence their pro- or anti-inflammatory effector function. We aimed to explore the interrelation between the Fc-glycosylation profile and disease transition, disease activity and outcome in patients with suspected and confirmed primary Sjögren's Disease (SjD). IgG Fc-sialylation and IgG Fc-galactosylation serum levels were determined in 300 patients from the Belgian Sjögren's Syndrome Transition Trial (BeSSTT). This cohort includes both suspected and confirmed SjD patients meeting the 2016 ACR/EULAR criteria. Salivary gland involvement was evaluated through ultrasonography (Hocevar score 0-48) and histopathology (focus score). The relative amount of sialylated and galactosylated IgG was determined by capillary electrophoresis after using the endoS endoglycosidase based assay. SjD patients exhibited significantly lower sialylation and galactosylation levels versus asymptomatic anti-SSA carriers and sicca patients. Lower sialylation and galactosylation levels were significantly associated with an increase in B-cell activation markers and distinct autoantibody profiles, particularly with multiple autoantibody reactivities. They were also linked to histopathological salivary gland alterations, higher Hocevar scores and importantly with risk factors for non Hodgkin lymphoma (NHL) development. In contrast, mono-anti-Ro60 positive and anti-SSA negative SjD patients had normal IgG Fc-glycosylation. This study points to a novel role of IgG Fc-glycosylation in SjD in predicting disease transition, monitoring disease activity, and risk stratification for NHL development.

Efficacy of combined administration of Baekhogainsam-Tang and low-dose pilocarpine on frequent intractable xerostomia: Study protocol for a randomized controlled trial.

Intractable xerostomia is defined as the subjective perception of dry mouth and persistent salivary gland hypofunction. Pilocarpine is an approved salivary sialagogue that is frequently prescribed for the treatment of intractable xerostomia; however, it often exhibits more side effects at high-doses and limited effectiveness at low-doses. Baekhogainsam-Tang (BIT) is a common herbal formula used by patients complaining of sore throats and thirst. It seems that BIT can compensate for the insufficient effect of low-dose pilocarpine. However, no clinical trials have studied the efficacy of combined administration of BIT and low-dose pilocarpine for intractable xerostomia. We aim to assess the non-inferior efficacy and fewer side effects of combined administration of BIT and low-dose pilocarpine compared with the administration of high-dose pilocarpine. A randomized, open-label, parallel-group, multi-center trial will be conducted. A total of 120 patients with Sjogren's syndrome having an unstimulated salivary flow rate (SFR) ≤0.1 mL/min or who have undergone radiotherapy to the head and neck with an unstimulated SFR ≤0.25 mL/min will be recruited competitively. They will be randomly allocated to either the experimental or control groups. The experimental group will receive BIT herbal granules three times and pilocarpine (2.5-mg) four times daily; meanwhile, the control group will receive only 5-mg pilocarpine four times daily for 12 weeks. The primary outcome is unstimulated SFR after 12 weeks of treatment. Secondary outcomes are stimulated SFR after 12 weeks of medication, as well as differences and mean percentage changes in unstimulated and stimulated SFR, visual analog scale, salivary scintigraphy, and questionnaires for both oral symptoms and quality of life during the clinical trial. An independent T test or Mann-Whitney U test will be performed to compare values between the two groups. The Paired T test or Wilcoxon signed-rank test will be performed to compare intragroup continuous values. This trial will be significant evidence on the efficacy and safety of combined use of BIT and low-dose pilocarpine to treat intractable xerostomia. The Clinical Research Information Service of the Republic of Korea (ISRCTN, KCT0005982). Registered on 10 February 2021.

A descriptive analysis of 21 patients with pulmonary amyloidosis: An observational study.

Pulmonary amyloidosis is an extremely rare disease, often detected incidentally because of its asymptomatic nature and potential to result in fatal outcomes. In this study, we aimed to present the clinical and radiological features of patients diagnosed with pulmonary amyloidosis by biopsy. This descriptive study included 21 patients with pathologically diagnosed pulmonary amyloidosis. Pulmonary amyloidosis was classified as diffuse alveolar-septal amyloidosis (DASA), cystic amyloidosis (CPA), tracheobronchial amyloidosis (TBA), nodular amyloidosis (NPA), and extraparenchymal pulmonary amyloidosis (pleural and mediastinal lymph node). Clinical, bronchoscopic, and radiological specific characteristics were presented in detail to be used for differential diagnosis. The median age of the patients was 63 (40-83) years, and 14 (66.7%) were male. Twenty patients (95.2%) presented with at least 1 comorbidity. All patients diagnosed with tracheobronchial amyloidosis were symptomatic at presentation, whereas those diagnosed with NPA/extraparenchymal amyloidosis were often asymptomatic. The patients included 1 case of DASA, 1 case of CPA, 10 cases of NPA, 6 cases of TBA, and 3 cases of extraparenchymal amyloidosis involving the mediastinal lymph node and pleura. Sixteen patients (76.2%) were classified as localized amyloidosis, while 5 patients (23.8%) were classified as systemic amyloidosis following the diagnosis of multiple myeloma, monoclonal gammopathy of undetermined significance, systemic lupus erythematosus, Sjogren's syndrome, and B-cell lymphoma. Bronchoscopic biopsies were sufficient for diagnosis, and notably, even transbronchial needle aspiration could be a useful diagnostic method. During the follow-up, we observed that the disease remained stable without progression. However, it is important to note that patients with concurrent malignancies experience fatal outcomes. In conclusion, it is crucial to distinguish pulmonary amyloidosis from other pulmonary diseases such as malignancies, infectious diseases, and interstitial lung diseases, which may have similar clinical and radiological findings. Bronchoscopic diagnostic methods are usually sufficient for the diagnosis. Although patients with pulmonary involvement mostly remain stable during long-term follow-up without progression, it is important to consider the risk of malignancy.

Classification of salivary gland biopsies in Sjögren's syndrome by a convolutional neural network using an auto-machine learning platform.

The histopathological analysis of minor salivary gland biopsies, particularly through the quantification of the Focus Score (FS), is pivotal in the diagnostic workflow for Sjögren's Syndrome (SS). AI-based image recognition using deep learning models has demonstrated potential in enhancing diagnostic accuracy and efficiency in preclinical research. The primary aim of this investigation was to utilize an auto-machine learning (autoML) platform for the automated segmentation and quantification of FS on histopathological slides, aiming to augment diagnostic precision and speed in SS. A cohort comprising 86 patients with sicca syndrome (37 diagnosed with SS based on the 2016 ACR/EULAR Classification Criteria and 49 non-SS) was selected for an in-depth histological examination. A repository of 172 slides (two per patient) was assembled, encompassing 74 slides meeting the classificatory thresholds for SS (FS ≥ 1, indicative of lymphocytic infiltration) and 98 slides showcasing normal salivary gland histology. The autoML platform utilized (Giotto, L2F, Lausanne Switzerland) employed a Convolutional Neural Network (CNN) architecture (ResNet-152) for the training and validation phases, using a dataset of 172 slides. The developed model exhibited a reliability score of 0.88, proficiently distinguishing SS cases, with a sensitivity of 89.47% (95% CI: 66.86% to 98.70%) and a specificity of 88.24% (95% CI: 63.56% to 98.54%). The model found histological slides of suboptimal quality (e.g., those compromised during fixation or staining processes) to be the most challenging for accurate classification. AutoML platforms offer a rapid and flexible approach to developing machine learning models, even with smaller datasets, as demonstrated in this study for SS. These platforms hold significant potential for enhancing diagnostic precision and efficiency in both clinical and research settings. Multicentric studies with larger patient cohorts are essential for thorough evaluation and validation of this innovative diagnostic approach.

Accuracy of Labial Salivary Gland Biopsy in Suspected Cases of Sjogren's Syndrome.

Sjögren's syndrome (SS) is a chronic autoimmune disorder primarily characterized by dysfunction of the exocrine glands, leading to dryness of the eyes and mouth (sicca symptoms). Labial salivary gland biopsy (LSGB) is a key diagnostic tool used to confirm SS through histopathological analysis. LSGB evaluates lymphocytic infiltration in the salivary glands, a hallmark of SS. Despite its utility, discrepancies between LSGB results and other diagnostic methods, like serology and clinical examination, persist. Given the potential for false negatives, especially in early-stage or mild diseases, LSGB is often used alongside other diagnostic tools. Assessing its diagnostic accuracy and correlation with clinical, demographic, and serological factors is critical for improving diagnostic precision in SS. This study aims to evaluate the diagnostic accuracy of LSGB in suspected SS cases, focusing on its correlation with clinical diagnoses, serological markers, and demographic factors. It also investigates whether LSGB can serve as a standalone diagnostic tool or should be integrated with other methods to enhance accuracy. This retrospective study evaluated 166 patients who underwent LSGB for suspected SS. Results were classified as "suggestive" or "not suggestive" of SS based on the histopathological evidence of lymphocytic infiltration. The relationship between LSGB outcomes and various demographics, serological markers, and the presence of other autoimmune diseases was examined. Statistical analyses assessed the significance of these associations. Categorical data were presented by frequency with percentage, and continuous data by mean with standard deviation (SD). Analyses were conducted using the Statistical Package for the Social Sciences (SPSS) version 27.0, with a P-value < 0.05 considered statistically significant. Among the 166 patients, 55 (33.1%) had LSGB results suggestive of SS, while 111 (66.9%) had non-suggestive findings. A significant association was found between antinuclear antibody (ANA) positivity and suggestive LSGB results (P = 0.003), indicating that ANA-positive patients were more likely to show histopathological evidence of SS. No significant associations were found with other serological markers, except for a near-significant trend with anti-Ro (anti-Ro/SSA antibodies) (P = 0.062). Age did not significantly influence biopsy outcomes (P = 0.580). The presence of other autoimmune diseases was significantly associated with suggestive LSGB findings (P = 0.034). LSGB remains a valuable diagnostic tool for SS, especially when serological and clinical findings are inconclusive. The study confirmed significant associations between ANA positivity and suggestive LSGB results, as well as the influence of other autoimmune diseases on histopathological outcomes. While Schirmer's test may detect ocular dryness, its correlation with LSGB findings was limited. LSGB should not be used as a standalone diagnostic measure but integrated with other tools, including serology and imaging, to improve accuracy. Future research should explore combining LSGB with salivary gland ultrasonography (SGUS) to enhance the detection of SS, particularly in early-stage or seronegative patients.