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RMD Open May 2024This study aimed to identify risk factors contributing to diverse pregnancy outcomes in primary Sjögren's syndrome (pSS) cases.
OBJECTIVES
This study aimed to identify risk factors contributing to diverse pregnancy outcomes in primary Sjögren's syndrome (pSS) cases.
METHODS
A retrospective analysis was conducted on pregnant individuals with pSS, who received outpatient or inpatient care across multiple hospitals in Anhui Province, China, from January 2015 to December 2022.
RESULTS
This study included 164 pregnant women with pSS and 328 control subjects, with no statistically significant difference in average age between the two groups. Analysis of pregnancy outcomes revealed that, compared with the control group, pregnant women in the pSS group were more likely to experience miscarriages, both spontaneous (12.80% vs 1.52%, p<0.001) and therapeutic (6.10% vs 0.91%, p<0.05). The proportion of placental abnormalities detected during prenatal ultrasound in women from the pSS group was higher (14.63% vs 6.40%, p<0.05). In the analysis of pregnancy outcomes for live-born neonates, a higher incidence of congenital heart abnormalities was observed in the pSS group (27.34% vs 12.03%, p<0.05). While there were no significant differences between the pSS pregnancies in terms of both normal and adverse pregnancy outcomes, a comparison of fetal survival and fetal loss in pSS pregnancies revealed a greater use of prophylactic anticoagulant therapy in the fetal survival group. Notably, the application of low molecular weight heparin (LMWH) emerged as an independent protective factor for fetal survival.
CONCLUSIONS
Compared with non-autoimmune controls, pregnancy in women with pSS presents more challenges. Importantly, we observed that the use of LMWH as anticoagulant therapy is an independent protective measure for fetal survival.
Topics: Humans; Female; Pregnancy; Sjogren's Syndrome; Adult; Pregnancy Outcome; Retrospective Studies; Pregnancy Complications; Risk Factors; China; Abortion, Spontaneous; Case-Control Studies; Heparin, Low-Molecular-Weight
PubMed: 38806189
DOI: 10.1136/rmdopen-2023-003616 -
Heliyon May 2024N7-methylguanosine (m7G) plays a crucial role in mRNA metabolism and other biological processes. However, its regulators' function in Primary Sjögren's Syndrome (PSS)...
OBJECTIVES
N7-methylguanosine (m7G) plays a crucial role in mRNA metabolism and other biological processes. However, its regulators' function in Primary Sjögren's Syndrome (PSS) remains enigmatic.
METHODS
We screened five key m7G-related genes across multiple datasets, leveraging statistical and machine learning computations. Based on these genes, we developed a prediction model employing the extreme gradient boosting decision tree (XGBoost) method to assess PSS risk. Immune infiltration in PSS samples was analyzed using the ssGSEA method, revealing the immune landscape of PSS patients.
RESULTS
The XGBoost model exhibited high accuracy, AUC, sensitivity, and specificity in both training, test sets and extra-test set. The decision curve confirmed its clinical utility. Our findings suggest that m7G methylation might contribute to PSS pathogenesis through immune modulation.
CONCLUSIONS
m7G regulators play an important role in the development of PSS. Our study of m7G-realted genes may inform future immunotherapy strategies for PSS.
PubMed: 38803884
DOI: 10.1016/j.heliyon.2024.e31307 -
Seminars in Arthritis and Rheumatism May 2024Classification criteria aim to identify a homogenous population of patients for research. We aimed to quantify how well phase-III trials in connective tissue diseases...
INTRODUCTION
Classification criteria aim to identify a homogenous population of patients for research. We aimed to quantify how well phase-III trials in connective tissue diseases (CTDs) represent a real-world cohort.
METHODS
A comprehensive review of all major published phase-III trials in CTDs was performed (clinicaltrials.gov). Classification criteria utilised most commonly in clinical trials were applied to a multicentre unselected CTD cohort.
RESULTS
There were 42 CTD trials identified, with no trials in mixed (MCTD) or undifferentiated CTD (UCTD). The majority of trials (N = 38, 90 %) required patients to meet classification criteria for their respective disease. Eight (19.0 %) excluded patients with overlapping CTDs and a further two (4.8 %) excluded specific overlapping features, such as pulmonary arterial hypertension. One study explicitly allowed overlap syndromes. Our real-world CTD cohort included 391 patients. Patients with UCTD or MCTD (91/391, 23.3 %) would be excluded from participation in clinical trials for not having an eligible diagnosis. Of patients with primary Sjögren's syndrome (pSS), SLE, systemic sclerosis (SSc) or idiopathic inflammatory myopathy (IIM), 211/300 (70.3 %) met the classification criteria for their respective diagnosis and 24/211 (11.4 %) met criteria for >1 CTD. In total, 187/391 (47.8 %) would be eligible for recruitment, based upon their physician diagnosis, and most stringent trial eligibility criteria.
CONCLUSION
In an unselected, real-world CTD cohort, up to half of patients are ineligible for clinical trials due to not meeting classification criteria, overlapping features or a lack of trials within their primary disease. To address this inequality in access to novel therapies, clinical trial design should evolve eligibility criteria in CTDs.
PubMed: 38796923
DOI: 10.1016/j.semarthrit.2024.152463 -
Journal of Personalized Medicine Apr 2024Functional gastrointestinal disorders (FGIDs), including functional dyspepsia (FD) and irritable bowel syndrome (IBS), are characterized by chronic and recurrent...
BACKGROUND
Functional gastrointestinal disorders (FGIDs), including functional dyspepsia (FD) and irritable bowel syndrome (IBS), are characterized by chronic and recurrent gastrointestinal symptoms. Clinically, FD and IBS often resemble gastrointestinal dysmotility caused by autoimmune autonomic neuropathy. We examined the seropositive frequency of autoantibodies against ganglionic nicotinic acetylcholine receptors (gnAChRs) in patients presenting with FGIDs.
OBJECTIVE
To elucidate the seropositivity of gnAChR antibodies and the clinical features of seropositive FD and IBS.
MATERIALS AND METHODS
We measured autoantibodies against the gnAChR α3 and β4subunits using luciferase immunoprecipitation systems. Serum samples from patients with any autonomic symptoms were obtained from hospitals in Japan between January 2012 and August 2018 (1787 serum samples of 1381 patients). We selected FD and IBS patients and compared the clinical characteristics and prevalence of autonomic symptoms between those with seropositive and seronegative IBS and FD.
RESULTS
Nine IBS and two FD cases (one comorbid case with IBS) were found. We found four patients (36.4%) in whom gnAChR antibodies were positive in these eleven patients. Sicca symptoms were observed in three of four cases (75%) of seropositive FGID compared with zero of seven cases (0%) of seronegative FGID.
CONCLUSIONS
We found patients with gnAChR antibodies in FD and IBS patients. These data will be valuable for elucidating the pathophysiology of these FGIDs and developing new treatment strategies.
PubMed: 38793066
DOI: 10.3390/jpm14050485 -
International Journal of Molecular... May 2024Sjögren's disease (SjD) is a heterogeneous autoimmune disease characterized by severe dryness of mucosal surfaces, particularly the mouth and eyes; fatigue; and chronic... (Review)
Review
Sjögren's disease (SjD) is a heterogeneous autoimmune disease characterized by severe dryness of mucosal surfaces, particularly the mouth and eyes; fatigue; and chronic pain. Chronic inflammation of the salivary and lacrimal glands, auto-antibody formation, and extra-glandular manifestations occur in subsets of patients with SjD. An aberrant expression of long, non-coding RNAs (lncRNAs) has been described in many autoimmune diseases, including SjD. Here, we review the current literature on lncRNAs in SjD and their role in regulating X chromosome inactivation, immune modulatory functions, and their potential as biomarkers.
Topics: Humans; Sjogren's Syndrome; RNA, Long Noncoding; Biomarkers; Animals; X Chromosome Inactivation; Gene Expression Regulation
PubMed: 38791207
DOI: 10.3390/ijms25105162 -
Genes May 2024Sjögren's disease (SjD) is a common systemic autoimmune disease that affects mainly women. Key pathologic features include the infiltration of exocrine glands by...
BACKGROUND
Sjögren's disease (SjD) is a common systemic autoimmune disease that affects mainly women. Key pathologic features include the infiltration of exocrine glands by lymphocytes and the activation of B lymphocytes with the production of autoantibodies. We aimed to analyze the transcriptome of circulating B cells from patients with SJD and healthy controls to decipher the B-cell-specific contribution to SJD.
METHODS
RNA from peripheral blood B cells of five untreated female patients with SjD and positive ANA, positive anti-SSA (both Ro-52 and Ro-60), positive anti-SSB and positive rheumatoid-factor, and five healthy controls was subjected to whole-transcriptome sequencing. A false discovery rate of < 0.1 was applied to define differentially expressed genes (DEG).
RESULTS
RNA-sequencing identified 56 up and 23 down DEG. Hierarchal clustering showed a clear separation between the two groups. Ingenuity pathway analysis revealed that these genes may play a role in interferon signaling, chronic mycobacterial infection, and transformation to myeloproliferative disorders.
CONCLUSIONS
We found upregulated expression of type-I and type-II interferon (IFN)-induced genes, as well as genes that may contribute to other concomitant conditions, including infections and a higher risk of myeloproliferative disorders. This adds insight into the autoimmune process and suggests potential targets for future functional and prognostic studies.
Topics: Humans; Sjogren's Syndrome; Female; B-Lymphocytes; Middle Aged; Transcriptome; Gene Expression Profiling; Interferons; Adult; Autoantibodies; Aged
PubMed: 38790257
DOI: 10.3390/genes15050628 -
Journal of Autoimmunity May 2024Autoreactive B cells and interferon (IFN) signature are hallmarks of primary sjögren's syndrome (pSS), but how IFN signaling pathways influence autoantibody production...
OBJECTIVES
Autoreactive B cells and interferon (IFN) signature are hallmarks of primary sjögren's syndrome (pSS), but how IFN signaling pathways influence autoantibody production and clinical manifestations remain unclear. More detailed studies hold promise for improved diagnostic methodologies and personalized treatment.
METHODS
We analyzed peripheral blood T and B cell subsets from 34 pSS patients and 38 healthy donors (HDs) at baseline and upon stimulation regarding their expression levels of type I and II IFN signaling molecules (STAT1/2, IRF1, IRF9). Additionally, we investigated how the levels of these molecules correlated with serological and clinical characteristics and performed ROC analysis.
RESULTS
Patients showed elevated IFN pathway molecules, including STAT1, STAT2 and IRF9 among most T and B cell subsets. We found a reduced ratio of phosphorylated STAT1 and STAT2 in patients in comparison to HDs, although B cells from patients were highly responsive by increased phosphorylation upon IFN stimulation. Correlation matrices showed further interrelations between STAT1, IRF1 and IRF9 in pSS. Levels of STAT1 and IRF9 in T and B cells correlated with the IFN type I marker Siglec-1 (CD169) on monocytes. High levels of STAT1 and IRF9 within pSS B cells were significantly associated with hypergammaglobulinemia as well as anti-SSA/anti-SSB autoantibodies. Elevated STAT1 levels were found in patients with extraglandular disease and could serve as a biomarker for this subgroup (p < 0.01). Notably, IRF9 levels in T and B cells correlated with EULAR Sjögren's syndrome disease activity index (ESSDAI).
CONCLUSION
Here, we provide evidence that in active pSS patients, enhanced IFN signaling incl. unphosphorylated STAT1 and STAT2 with IRFs entertain chronic T and B cell activation. Furthermore, increased STAT1 levels candidate as biomarker of extraglandular disease, while IRF9 levels can serve as biomarker for disease activity.
PubMed: 38788537
DOI: 10.1016/j.jaut.2024.103243 -
Farmacia Hospitalaria : Organo Oficial... May 2024To study the physicochemical and microbiological stability over 90 days of two preservative-free methylprednisolone sodium succinate (MTPSS) 1 and 10 mg/mL eye drops...
OBJECTIVE
To study the physicochemical and microbiological stability over 90 days of two preservative-free methylprednisolone sodium succinate (MTPSS) 1 and 10 mg/mL eye drops for use in ocular pathologies such as Sjögren's syndrome and dry eye syndrome.
METHOD
The two eye drops were prepared from injectable MTPSS (Solu-moderin® and Urbason®), water for injection and normal saline solution. In accordance with ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use) guidelines, they were then stored in triplicate under refrigerated conditions (5±3 °C), at room temperature (25±2 °C), and at 40 °C (±2 °C). In accordance with the USP (United States Pharmacopeia), physicochemical controls of the active ingredient content were carried out by HPLC-UV (High Performance Liquid Chromatography with Ultraviolet detection), together with controls of pH, osmolality, and visual examination. Microbiological sterility was also tested under refrigerated conditions up to 30 days in open containers and up to 90 days in closed ones.
RESULTS
The eye drops stored at 5 °C were the most stable; in the 1 mg/mL eye drops, degradation of the drug fell below 90% from day 21, and in the 10 mg/mL eye drops, from day 42. pH change did not vary by ≥1 unit in formulations stored at 5 °C, unlike the other formulations. Changes in osmolality did not exceed 5% on day 90 in any storage conditions. Samples of non refrigerate eye drops at 10 mg/mL, presented a white precipitate from day 14 and 28, respectively. Non-refrigerated 1 mg/mL eye drops presented suspended particles on day 90. There were no color changes. Microbiological analysis showed that sterility was maintained for over 90 days in the closed containers, although microbial contamination was detected from day 21 in the open containers.
CONCLUSIONS
1 mg/mL MTPSS eye drops show physicochemical and microbiological stability for 21 days under refrigeration, compared to 42 days for 10 mg/mL eye drops stored under the same conditions. However, since they do not include preservatives in their composition, they should not be used for more than 7 days after opening.
PubMed: 38782645
DOI: 10.1016/j.farma.2024.04.021 -
JCI Insight May 2024Dendritic cell inhibitory receptor (DCIR) is a C-type lectin receptor selectively expressed on myeloid cells, including monocytes, macrophage, dendritic cells, and...
Dendritic cell inhibitory receptor (DCIR) is a C-type lectin receptor selectively expressed on myeloid cells, including monocytes, macrophage, dendritic cells, and neutrophils. Its role in immune regulation has been implicated in murine models and human genome-wide association studies (GWAS), suggesting defective DCIR function associates with increased susceptibility to autoimmune diseases such as rheumatoid arthritis, lupus and Sjogren's syndrome. However, little is known about the mechanisms underlying DCIR activation to dampen inflammation. Here, we developed anti-DCIR agonistic antibodies that promote phosphorylation on DCIR's immune receptor tyrosine-based inhibitory motifs (ITIM) and recruitment of SH2 containing protein tyrosine phosphatase-2 (SHP2) for reducing inflammation. We also explored the inflammation resolution by depleting DCIR+ cells with antibodies. Utilizing a human DCIR knock-in mouse model, we validated the anti-inflammatory properties of the agonistic anti-DCIR antibody in experimental peritonitis and colitis. These findings provide critical evidence for targeting DCIR to develop transformative therapies for inflammatory diseases.
PubMed: 38781017
DOI: 10.1172/jci.insight.176064 -
Archives of Rheumatology Mar 2024The aim of our study was to investigate whether TNFAIP3, PTPN22, and TRAF1-5 single nucleotide polymorphisms (SNPs) are associated with susceptibility, severity, or...
OBJECTIVES
The aim of our study was to investigate whether TNFAIP3, PTPN22, and TRAF1-5 single nucleotide polymorphisms (SNPs) are associated with susceptibility, severity, or serological markers in primary Sjögren's syndrome (pSS).
PATIENTS AND METHODS
The cases and controls study was conducted between December 2021 and June 2022. TNFAIP3 rs10499194C/T, rs6920220G/A, and rs2230926T/G, PTPN22 rs2476601C/T and rs33996649G/A, and TRAF1-C5 rs10818488G/A polymorphisms were genotyped in 154 female pSS patients (mean age: 45.2±6.8 years) and 313 female control subjects (mean age: 50.3±7.5 years) using the TaqMan® SNP genotyping assay. An association analysis between TNFAIP3, PTPN22, and TRAF1-C5 SNPs and susceptibility, clinical characteristics, and serological markers of pSS was performed. Interactions between TNFAIP3, PTPN22, and TRAF1-C5 SNPs were also evaluated in patients and controls.
RESULTS
The genotype and allele frequencies showed no association with susceptibility, severity, or serological markers of pSS. Nevertheless, several interactions between TNFAIP3 and TRAF1-C5 or TNFAIP3, PTPN22, and TRAF1-C5 genotypes were associated with susceptibility to pSS (p<0.01).
CONCLUSION
Individual TNFAIP3, PTPN22, and TRAF1-C5 SNPs are not associated with susceptibility, severity, or serological markers of pSS. However, genetic interactions between TRAF1-C5 and TNFAIP3 or TNFAIP3, PTPN22, and TRAF1-C5 SNPs are risk factors for pSS.
PubMed: 38774701
DOI: 10.46497/ArchRheumatol.2024.10108