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ID PMID Title PublicationDate abstract
34603337 Novel Roles of the Tim Family in Immune Regulation and Autoimmune Diseases. 2021 T cell Ig and mucin domain (Tim) protein family members were identified to be important regulators of the immune response. As their name indicates, Tim proteins were originally considered a T cell-specific markers, and they mainly regulate the responses of T helper cells. However, accumulating evidence indicates that Tims are also expressed on antigen-presenting cells (APCs), such as monocytes, macrophages, dendritic cells (DCs) and B cells, and even plays various roles in natural killer cells (NKs) and mast cells. In recent years, the expression and function of Tims on different cells and the identification of new ligands for the Tim family have suggested that the Tim family plays a crucial role in immune regulation. In addition, the relationship between Tim family gene polymorphisms and susceptibility to several autoimmune diseases has expanded our knowledge of the role of Tim proteins in immune regulation. In this review, we discuss how the Tim family affects immunomodulatory function and the potential role of the Tim family in typical autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and type 1 diabetes (T1D). A deeper understanding of the immunoregulatory mechanism of the Tim family might provide new insights into the clinical diagnosis and treatment of autoimmune diseases.
34347374 A bond between rheumatic diseases and cancer in the elderly: The interleukin-6 pathway. 2021 Oct Interleukin (IL)-6 is a soluble factor secreted by T lymphocytes, involved in antibody generation by B lymphocytes. The IL-6 pathway has risen as a pivotal pathway implicated in immune regulation and dysregulation in various rheumatic diseases. Nonetheless, elevated IL-6 levels can also play a role in cancer. Targeting the IL-6 pathway has led to innovative therapeutic approaches for rheumatic diseases and for COVID-19, particularly in the elderly. Indeed, tocilizumab, an agent targeting IL-6, has recently amassed significant attention as a promising univocal agent for different conditions. In this viewpoint, we sought to recall and describe the common pathway among osteoarthritis, rheumatoid arthritis, and cancer, suggesting that anti-IL-6 may be considered a jack-of-all-trades against inflammaging in the elderly.
34228239 CCN proteins in the musculoskeletal system: current understanding and challenges in physio 2021 Dec The acronym for the CCN family was recently revised to represent "cellular communication network". These six, small, cysteine-enriched and evolutionarily conserved proteins are secreted matricellular proteins, that convey and modulate intercellular communication by interacting with structural proteins, signalling factors and cell surface receptors. Their role in the development and physiology of musculoskeletal system, constituted by connective tissues where cells are interspersed in the cellular matrix, has been broadly studied. Previous research has highlighted a crucial balance of CCN proteins in mesenchymal stem cell commitment and a pivotal role for CCN1, CCN2 and their alter ego CCN3 in chondrogenesis and osteogenesis; CCN4 plays a minor role and the role of CCN5 and CCN6 is still unclear. CCN proteins also participate in osteoclastogenesis and myogenesis. In adult life, CCN proteins serve as mechanosensory proteins in the musculoskeletal system providing a steady response to environmental stimuli and participating in fracture healing. Substantial evidence also supports the involvement of CCN proteins in inflammatory pathologies, such as osteoarthritis and rheumatoid arthritis, as well as in cancers affecting the musculoskeletal system and bone metastasis. These matricellular proteins indeed show involvement in inflammation and cancer, thus representing intriguing therapeutic targets. This review discusses the current understanding of CCN proteins in the musculoskeletal system as well as the controversies and challenges associated with their multiple and complex roles, and it aims to link the dispersed knowledge in an effort to stimulate and guide readers to an area that the writers consider to have significant impact and relevant potentialities.
34136315 A Review of the Efficacy of Influenza Vaccination in Autoimmune Disease Patients. 2021 May 13 Patients suffering from autoimmune diseases appear to be at greater risk for developing infections with the influenza virus compared to healthy controls due to their immunosuppressive treatment, suggesting the importance of vaccination. Within this literature review, we highlight the importance, efficacy, and safety of influenza vaccination in individuals with autoimmune diseases, including systemic lupus erythematosus (SLE), Sjogren syndrome (SS), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD) in both vaccinated and unvaccinated individuals. Overall, vaccination is generally well tolerated by SLE patients and the literature recommends the inactivated influenza vaccine to SLE patients according to the recommendations and schedules for the general population and annually against seasonal influenza viruses. While the data are still unclear in patients with SS, there does seem to be a general consensus to vaccinate these individuals to prevent harmful risks of influenza disease. In patients with RA and IBD, vaccination efficacy with the inactivated influenza vaccine should be determined on a case-by-case basis, taking patient therapy into account. In light of the current pandemic and global coronavirus disease 2019 (COVID-19) crisis, it is crucial to emphasize the safety and immunogenicity of influenza vaccination in vulnerable individuals suffering from autoimmune diseases. Public health measures are recommended to protect these individuals with vaccinations, keeping in mind the possibility of the multiple COVID-19 vaccines that are currently available.
33841739 Rheumatoid arthritis associated with the occurrence, severity and extension of periodontit 2021 Apr BACKGROUND: Emerging evidence pointed to a potential association between periodontitis (PE) and rheumatoid arthritis (RA), based on shared characteristics and similarities in risk factors, immunogenetics and pathways of tissue destruction. The aim of this study was to evaluate the potential association between RA and PE, as well as the influence of risk variables in this association. MATERIAL AND METHODS: The present case-control study comprised 471 individuals (157 cases with RA and 314 controls) that underwent a full-mouth periodontal examination. The association between risk variables and the occurrence of AR and PE were evaluated through univariate and multivariate logistic analysis. RESULTS: Higher frequency (p<0.001), severity (p=0.006) and extension (p=0.018) of PE was observed among the cases when compared to controls. Variables retained in the final multivariate models for the occurrence of PE were: lower number of teeth, smoking, no use of dental floss, ≥4 daily toothbrushing and RA; for the occurrence of RA were: higher age, female gender, smoking, alcohol use and PE. It is important to stress that RA (OR=2.53; 95%CI 1.24-3.86; p<0.001) was retained in the model for PE, and PE (OR=3.12; 95%CI 1.47-4.26; p<0.001) was retained in the model for RA. CONCLUSIONS: The present study demonstrated a high frequency of PE among individuals with RA and an important association among the occurrence, severity and extension of PE and RA and smoking. Key words:Case-control study, risk factors, periodontitis, rheumatoid arthritis.
34959607 The Effect of Acknowledged and Novel Anti-Rheumatic Therapies on Periodontal Tissues-A Nar 2021 Nov 23 Rheumatoid arthritis (RA) and periodontal disease (PD) are chronic complex inflammatory diseases with several common susceptibility factors, especially genetic and environmental risk factors. Although both disorders involve a perturbation of the immune-inflammatory response at multiple levels, one major difference between the two is the different locations in which they develop. RA is triggered by an exaggerated autoimmune response that targets joints, while periodontal disease occurs as a consequence of the subgingival periodontopathogenic microbiota. Current treatment models in both pathologies involve the stratification of patients to allow therapeutic individualization according to disease stage, complexity, progression, lifestyle, risk factors, and additional systemic diseases. Therapeutic guidelines for RA comprise of five main classes of drugs: non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, glucocorticoids, and disease-modifying anti-rheumatic drugs (DMARDs): biologic and non-biologic. Although various treatment options are available, a definitive treatment remains elusive, therefore research is ongoing in this area. Several alternatives are currently being tested, such as matrix metalloproteinases (MMP) inhibitors, toll-like receptors (TLR) blockers, pro-resolution mediators, anti-hypoxia inducing factors, stem cell therapy, NLRP3 inhibitors and even natural derived compounds. Although the link between PD and rheumatoid arthritis has been investigated by multiple microbiology and immunology studies, the precise influence and causality is still debated in the literature. Furthermore, the immunomodulatory effect of anti-rheumatic drugs on the periodontium is still largely unknown. In this narrative review, we explore the mechanisms of interaction and the potential influence that anti-rheumatoid medication, including novel treatment options, has on periodontal tissues and whether periodontal health status and treatment can improve the prognosis of an RA patient.
33586127 Serum KL-6, CA19-9, CA125 and CEA are Diagnostic Biomarkers for Rheumatoid Arthritis-Assoc 2021 Mar INTRODUCTION: This study aimed to evaluate the role of tumor marker carbohydrate antigen (CA) 125 (CA125), CA19-9, carcinoembryonic antigen (CEA) and Krebs von den Lungen-6 (KL-6) in the diagnosis and determination of the severity of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. METHODS: A retrospective analysis was performed. Fifty RA patients (24 patients with ILD and 26 patients without ILD), 10 healthy subjects and 14 patients with other connective tissue disease-associated interstitial lung disease were included. Serum levels of KL-6 and tumor markers CA19-9, CA125 and CEA were measured. Chest HRCT of patients with ILD was scored quantitatively according to the degree of fibrosis. Data on the C-reactive protein, erythrocyte sedimentation rate, rheumatoid factors and anti-cyclic peptide containing citrulline (anti-CCP) were also collected. RESULTS: Serum levels of KL-6, CA19-9, CA125 and CEA in the RA-ILD group were significantly higher than those in the RA-no-ILD group. The serum KL-6 level was positively correlated with the HRCT fibrosis score (r = 0.63, p = 0.002). The logistic regression analysis showed that CA19-9 and smoking were associated with RA-ILD [OR = 1.118, 95% CI = (1.038, 1.204), p = 0.003 for CA19-9, OR = 14.969, 95% CI = (1.750, 128.043), p = 0.013 for smoking]. CONCLUSIONS: KL-6 level and tumor markers were elevated in RA-ILD, and strongly associated with the severity of ILD, supporting their value as pathogenically relevant biomarkers, which can contribute to noninvasive detection of this extra-articular disease complication.
33648502 Deciphering potential pharmacological mechanism of Sha-Shen-Mai-Dong decoction on primary 2021 Mar 1 BACKGROUND: Sha-Shen-Mai-Dong decoction (SSMD) is a classical prescription widely used in primary Sjogren's Syndrome (pSS) therapy. This study aims to explore the potential pharmacological mechanism of SSMD on pSS. METHODS: Active components of SSMD were obtained from Traditional Chinese Medicine Integrative Database and Traditional Chinese Medicine Systems Pharmacology databases and targets of SSMD were predicted by Pharmmapper and STITCH database. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out to explore the function characteristics of SSMD. The expression matrix of microarray of pSS was obtained from Gene Expression Omnibus and we obtained 162 differentially expressed genes (DEGs). Protein-protein interaction (PPI) networks were constructed to identify the hub targets. Principal component analysis (PCA) and molecular docking were conducted to further elucidate the possibility of SSMD for pSS. RESULTS: SSMD contained a total of 1056 active components, corresponding to 88 targets, among which peripheral myelin protein 2(PMP2), androgen receptor (AR) and glutamic acid decarboxylase 1(GAD1) are associated with multiple active components in SSMD and may be the core targets. Moreover, these targets were closely related to tissue pathological injury in SS, such as lacrimal gland, salivary gland and nervous system injury. GO and KEGG analysis showed that 88 targets enriched in REDOX process, transcriptional regulation and negative regulation of apoptosis process. Besides, SSMD may influence the cell proliferation, gene transcription through regulating Ras and cAMP-related signaling pathways. In addition, SSMD may show effects on immune regulation, such as macrophage differentiation, Toll-like receptor 4 signaling pathway and T-helper 1 in SS. Moreover, PPI network suggested that FN1, MMP-9 may be the hub targets in SSMD. Result of PCA and molecular docking analysis further determined the feasibility of SSMD in treating pSS. CONCLUSION: SSMD can regulate multiple biological processes by virtue of its multiple active components, thus showing prominent advantage in the treatment of pSS. The discovery of active ingredients and targets in SSMD provides valuable resources for drug research and development for pSS.
33611611 CIDP associated with Sjögren's syndrome. 2021 Aug BACKGROUND: This study addresses the challenging characterisation and differentiation of CIDP versus CIDP in association with Sjögren's syndrome to facilitate the process in clinical routine. METHODS: Patients with both CIDP and Sjögren's syndrome and CIDP without Sjögren's syndrome were compared concerning relevant differences in clinical, laboratory and electrophysiological findings. 154 patients who fulfilled the diagnostic EFNS/PNS criteria for CIDP were included in the analysis. 54 of these patients additionally fulfilled the ACR/EULAR classification criteria for Sjögren's syndrome. RESULTS: The frequency of female patients was higher in patients with CIDP and Sjögren's syndrome (52%) versus CIDP patients without Sjögren's syndrome (28%). Furthermore, the occurrence of cranial nerve impairment was significantly higher in patients with Sjögren's syndrome (39% versus 14%). There were no significant group differences in the evaluation of initial symptoms, severity of disability judged by INCAT disability scale score, presence or distribution of sensory deficits, limb weakness and the presence of ataxia, pain or dysautonomia, CSF laboratory or electrophysiological findings. CONCLUSIONS: In conclusion, our data indicate that cranial nerve impairment and female gender might represent red flags for an additional Sjögren's syndrome in patients with CIDP. The patterns of clinical disabilities and electrophysiological findings due to peripheral nerve damage are similar in both CIDP entities.
33976464 Clinical manifestations of Whipple's disease mimicking rheumatic disorders. 2021 Whipple's disease is a rare, chronic, systemic disorder caused by Tropheryma whipplei infection. The most common symptoms are weight loss, arthralgia, diarrhea and abdominal pain. Other organ involvement can also occur in the patients. Joint manifestations may mimic rheumatoid arthritis or spondyloarthritis. Arthalgia, arthritis, spondylodiscitis, bursitis and/or tenosynovitis are seen in the majority of the patients. This explains why some of the symptoms are misdiagnosed as those of rheumatic diseases. Understanding of Whipple's disease is important for differential diagnostics of several rheumatic symptoms.
34205846 Increased Risk of Sjögren's Syndrome in Patients with Obsessive-Compulsive Disorder: A Na 2021 Jun 1 Obsessive-compulsive disorder (OCD) includes a wide range of symptoms and is often associated with comorbidities. Although psychiatric involvement may be an early manifestation of Sjögren's syndrome (SS), only a few studies have demonstrated the relationship between OCD and SS. This is a nationwide cohort study identifying the risk of SS in OCD patients. We studied a longitudinal health insurance database for the period from 1999 to 2013. The study group was OCD patients with at least three outpatient visits or one hospitalization. The comparison cohort was matched by age and sex, as well as comorbidities. We calculated the risk of Sjögren's syndrome using Cox proportional hazard regression models. We performed a propensity score match for confounders and effect modifiers between the two groups. The propensity score probability was estimated through logistic regression. Primary outcome was the incidental SS. A total of 1678 patients with OCD (49% women, mean age: 35.6 years) and 3356 controls were followed up, resulting in 13,077 and 25,856 person-years, respectively. The hazard ratio for developing SS was 3.31 (95% C.I.: 1.74-6.28) in patients with OCD, compared to those without OCD after adjusting for age, sex, and comorbidities. Furthermore, the risk of SS significantly increased over the 2-year follow-up period after OCD diagnosis. We concluded that risk of SS is significantly increased in patients with OCD compared to those without OCD. Clinically, Sjögren's symptoms in OCD patients should be regularly assessed.
34128801 Factors influencing the EULAR Sjögren's Syndrome Patient-Reported Index in primary Sjögr 2021 Nov OBJECTIVES: The ESSPRI is a validated tool for measuring pain, fatigue and dryness in primary Sjögren's syndrome (pSS). We evaluated its association with disease and non-disease related variables, and its variation though the follow-up. METHODS: We included 130 pSS patients who were interviewed to register demographics, schooling, smoking, menopause, body mass index (BMI), disease duration, use of hormonal replacement, associated sicca drugs, prednisone, immunosuppressors/antimalarials, comorbidities such as diabetes mellitus, hypothyroidism, depression, fibromyalgia and scored the Charlson comorbidity index. We assessed the non-stimulated whole salivary flow (NSWSF), Schirmer-I test, ESSDAI and ESSPRI scores. In a subset of patients, we scored a second ESSPRI. RESULTS: Most patients were women, mean age 57 years and median disease duration 9.3 years. The median ESSPRI score was 6 (fatigue 6, pain 4, dryness 8). Eighty patients (61.5%) had an ESSPRI ≥5 points and were characterized by a higher prevalence of depression (OR 3.7, 95% 1.2-11.3) and lower NSWSF (OR 0.59, 95% CI 0.36-0.97). Among 62 patients with a second ESSPRI (median time 25 months), 44 (70%) experienced a decrement/increment ≥1 in the ESSPRI (16 were decrement). We did not find any of the studied variables associated with this variation, also including change in prednisone or immunosuppressors. CONCLUSIONS: An ESSPRI ≥5 (unsatisfactory symptom state) was associated with low NSWSF and depression. Most of the patients experienced a clinically significant ESSPRI variation (increment or decrement), nevertheless, we were not able to identify any variable associated with this change. Further studies would be helpful to understand the underlying causes.
33771203 Sjogren's syndrome in clinical trials of traditional Chinese medicine: protocol for the de 2021 Mar 26 BACKGROUND: Sjogren's syndrome (SS) is a chronic autoimmune rheumatic disease with an incidence of 0.03 to 0.3%. In recent years, there are an increasing number of randomized controlled trials of traditional Chinese medicine (TCM) for SS. However, there are generally some problems in these published clinical trials: lack of reporting primary or long-term outcomes and the heterogeneous in different clinical trials' outcome. Our study aims to determine the priority outcomes and standard TCM syndromes for all stakeholders and reach agreement on the COS and syndromes to be measured and reported in all future TCM trials in patients with SS. METHODS AND ANALYSIS: A phase-wise refinement approach will be used, consisting of three phases, yet complementary, sub-work phases, whereby each phase will inform the next coming phases. The following are the three phases: (I-a) identifying of a long initial list of outcomes through systematic literature review and semi-structured qualitative interviews and (I-b) identifying an initial list of TCM syndromes through (1) systematic literature review, (2) referencing ancient Chinese medical books, and (3) retrospective studies of medical records; (II) prioritization of outcomes using Delphi survey with different stakeholders, such as health professionals and patients; and (III) through consensus meetings with patients and professionals to agree on the final COS and TCM syndromes. DISCUSSION: We summarized the actions of COS into three points: direct action, indirect action, and final action. After the final COSs is completed, we will publish this research in a journal to promote communication. TRIAL REGISTRATION: Core Outcome Measures in Effectiveness Trials Initiative (COMET) number 1429 . Registered on 01 December 2019.
33404641 Dissecting the clinical heterogeneity of adult-onset Still's disease: results from a multi 2021 Oct 2 OBJECTIVES: To stratify adult-onset Still's disease (AOSD) patients in distinct clinical subsets to be differently managed, by using a multi-dimensional characterization. METHODS: AOSD patients were evaluated by using a hierarchical unsupervised cluster analysis comprising age, laboratory markers systemic score and outcomes. The squared Euclidean distances between each pair of patients were calculated and put into a distance matrix, which served as the input clustering algorithm. Derived clusters were descriptively analysed for any possible difference. RESULTS: Four AOSD patients clusters were identified. Disease onset in cluster 1 was characterized by fever (100%), skin rash (92%) and arthritis (83%), with the highest ferritin levels [mean (S.D.) 14 724  (6837) ng/ml]. In cluster 2, the onset was characterized by fever (100%), arthritis (100%) and liver involvement (90%), together with the highest CRP levels [288.10  (46.01) mg/l]. The patients in cluster 3 presented with fever (100%), myalgia (96%) and sore throat (92%). The highest systemic score values [8.88  (1.70)] and the highest mortality rate (54.2%) defined cluster 3. Fever (100%) and arthritis (90%) were the symptoms at the onset in cluster 4, which was characterized by the lowest ferritin and CRP levels [1457  (1298) ng/ml and 54.98  (48.67) mg/l, respectively]. CONCLUSION: Four distinct phenotypic subgroups in AOSD could be suggested, possibly associated with different genetic background and pathogenic mechanisms. Our results could provide the basis for a precision medicine approach in AOSD in an attempt to find a clinical and laboratory multidimensional stratification and characterization, which would drive a tailored therapeutic approach in these patients.
33323573 Does Sjogren's syndrome affect only the lacrimal gland in the eye? Time to replace the mis 2021 Jan PURPOSE: This study aimed to reveal the cause of meibomian gland disease and meibomian gland loss in patients with Sjögren's syndrome (SS) as the leading factor for dry eyes. METHODS: The study included a total of 30 patients with SS and dry eye symptoms and a control group of 50 age- and gender-matched healthy subjects. The dryness parameters of all the participants were evaluated. At first, meibography was performed to measure meibomian gland loss using noninvasive methods. Later, meibomian gland expression and secretion quality were evaluated using silt-lamp biomicroscopy. Correlations between the measurements were analyzed statistically. RESULTS: In patients with SS, MG loss was significantly greater than in the control group (19.7 ± 71%, 12.7 ± 9.6%, P < 0.001). All dry eye parameters (tear film breakup time, Schirmer's test score, OSDI, stain score, dry eye disease) were statistically significant in the SS group. There was an extremely negative correlation between upper MB loss and BUT (P = 0.08, r: 0.781). There was an extremely positive correlation between upper MB loss and staining (P = 0.015, r: 0.739). An extremely negative correlation was determined between sub-MB loss and BUT (P = 0.18, r:-0.781), and a moderately positive significant correlation was found between sub-MB loss and staining (P = 0.031, r: 0.659). CONCLUSION: The results of this study demonstrated that patients with SS were at a higher risk of being exposed to meibomian gland loss, which directly leads to the severe dry eye symptoms associated with SS.
31034046 Treatment of Sjögren's syndrome: current therapy and future directions. 2021 May 14 SS is usually described as having severe fatigue, dryness, diffuse pain, glandular swelling, and various extraglandular (systemic) manifestations. Clinical trials have generally failed because the vast majority of enrolled patients had no extraglandular manifestations at the time of enrolment but suffered from fatigue, dryness and pain that did not significantly respond to the study medication. A number of hypotheses on the pathogenesis of pSS have been put forward, including disturbances of innate and adaptive immunity as well as abnormalities of the interface between immune disorders and the neuro-endocrine system related to lacrimal and secretory gland dysfunction. Thus, future therapies must be designed for improvement of the symptoms of dry eyes and dry mouth, extraglandular disease, and fatigue and cognitive deficits. Given the inadequacies and limitations of current treatment options, we suggest that innovative directions involving interactions with neuroscientists and neuropsychiatrists together or combined with new immune targeting may be hold promise for better treating pSS.
34694689 Asymptomatic myocardial dysfunction was revealed by feature tracking cardiac magnetic reso 2021 Dec AIM: To evaluate subclinical left ventricular (LV) regional dysfunction in patients with primary Sjögren's syndrome (pSS) using feature tracking cardiac magnetic resonance (FT-CMR) imaging and to identify pSS characteristics independently associated with LV regional dysfunction. METHOD: Fifty patients with pSS and 20 controls without cardiovascular disease underwent non-contrast CMR imaging. Labial gland biopsy was performed in 42 patients (84%). Disease activity was assessed using the European League Against Rheumatism Sjögren's syndrome disease activity index (ESSDAI). LV global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were measured using FT-CMR. RESULTS: No significant differences in cardiovascular risk factors were found between the pSS group and controls. The pSS group had significantly lower GLS (P = .015) and GCS (P = .008) than the control group. Multiple linear regression analysis indicated that GCS was significantly associated with Raynaud's phenomenon (P = .015), focus score ≥2 (P = .032), and total ESSDAI score ≥8 (P = .029). CONCLUSION: FT-CMR can reveal subclinical LV regional dysfunction in patients with pSS without cardiovascular disease. Furthermore, patients with pSS and Raynaud's phenomenon, a focus score ≥2, or an ESSDAI score ≥8 were considered to be at high risk for myocardial dysfunction.
34418167 A rare case of pulmonary nocardiosis comorbid with Sjogren's syndrome. 2021 Sep BACKGROUND: Nocardia is an opportunistic pathogen, which occurs in patients with autoimmune diseases and immune dysfunction, and can cause bacteremia and other life-threatening complications. The clinical manifestations of Nocardia pneumonia are similar to tuberculous and other clinical common bacterial pneumonia, but its antibacterial treatments are different and detection methods are unique, which may lead patients to suffer for many years due to clinical misdiagnosis and missed diagnosis. METHODS: Imaging and laboratory examinations were performed for preliminary diagnosis, and next-generation sequencing was used to identify the exact species type of Nocardia in the bronchoalveolar lavage fluid (BALF) of the patient. RESULTS: Imaging and laboratory parameters preliminarily implied that the patient was infected with Nocardia with Sjogren's syndrome (SS), and NGS showed that the strain was N. terpenica. CONCLUSIONS: Accurate etiological diagnosis and corresponding antibiotics are key to improve the prognosis of pulmonary nocardiosis in this case. Nocardia pneumonia is rare in clinical practice; it is of great medical significance to improve the understanding of pulmonary nocardiosis.
34298409 Interferon (IFN)-stimulated gene 15: A novel biomarker for lymphoma development in Sjögre 2021 Sep OBJECTIVE: We investigated whether interferon (IFN) induced genes could serve as biomarkers for the detection of lymphoma development among patients with Sjögren's syndrome (SS). METHODS: Total RNA was extracted from 98 labial minor salivary glands (LMSG) biopsies of SS patients [61 not complicated by lymphoma (SS-nL) and 37 complicated by Non-Hodgkin Lymphoma (NHL) (SS-L)] and 67 matched peripheral blood (PB) samples, as well as from 30 LMSG biopsies and 17 matched PB derived from sicca controls (SC). RNA sequencing was performed in LMSG biopsies of high and low risk SS patients for lymphoma development and SC. Expression analysis of type I (MX-1, IFIT-1, IFI44 and ISG-15) and type II IFN induced (CXCL9/MIG-1, GBP-1) genes was performed by real time PCR. RESULTS: ISG-15 transcript levels were significantly higher in SS-L patients compared to SS-nL patients in both LMSG tissues and PB specimens. Additionally, MIG-1 was found to display higher expression values in LMSG tissues, but not in PB derived from SS-L patients compared to the SS-nL group. A coordinate expression in PB/LMSG of type I IFN (ISG-15, MX-1 and IFI44), but not type II IFN induced genes was also observed. CONCLUSION: ISG-15 gene expression was able to distinguish SS-nL and SS-L at both periphery and tissue level and therefore could represent a novel biomarker for lymphoma development among SS patients. PB and LSMG seem to share a common transcriptional profile of type I IFN pathway.
34045583 Gene expression alterations in salivary gland epithelia of Sjögren's syndrome patients ar 2021 May 27 Sjögren's syndrome (SS) is a complex autoimmune disease associated with lymphocytic infiltration and secretory dysfunction of salivary and lacrimal glands. Although the etiology of SS remains unclear, evidence suggests that epithelial damage of the glands elicits immune and fibrotic responses in SS. To define molecular changes underlying epithelial tissue damage in SS, we laser capture microdissected (LCM) labial salivary gland epithelia from 8 SS and 8 non-SS controls for analysis by RNA sequencing (RNAseq). Computational interrogation of gene expression signatures revealed that, in addition to a division of SS and non-SS samples, there was a potential intermediate state overlapping clustering of SS and non-SS samples. Differential expression analysis uncovered signaling events likely associated with distinct SS pathogenesis. Notable signals included the enrichment of IFN-γ and JAK/STAT-regulated genes, and the induction of genes encoding secreted factors, such as LTF, BMP3, and MMP7, implicated in immune responses, matrix remodeling and tissue destruction. Identification of gene expression signatures of salivary epithelia associated with mixed clinical and histopathological characteristics suggests that SS pathology may be defined by distinct molecular subtypes. We conclude that gene expression changes arising in the damaged salivary epithelia may offer novel insights into the signals contributing to SS development and progression.