Autoimmune Diseases Research Articles

Cancer and Autoimmune Diseases as Two Sides of Chronic Inflammation - and the Method of Therapy.

Chronic inflammation is associated with a prolonged increase in various inflammatory factors. According to clinical data, it can be linked with both cancer and autoimmune diseases in the same patients. This raises the critical question of how chronic inflammation relates to seemingly opposing diseases - tumors, in which there is immunosuppression, and autoimmune diseases, in which there is over-activation of the immune system. In this review, we consider chronic inflammation as a prerequisite for both immune suppression and an increased likelihood of autoimmune damage. We also discuss potential disease-modifying therapies targeting chronic inflammation, which can be helpful for both cancer and autoimmunity. On the one hand, pro-inflammatory factors persisting in the areas of chronic inflammation stimulate the production of anti-inflammatory factors due to a negative feedback loop, eliciting immune suppression. On the other hand, chronic inflammation can bring the baseline immunity closer to the threshold level required for triggering an autoimmune response using the bystander activation of immune cells. Focusing on the role of chronic inflammation in cancer and autoimmune diseases may open prospects for more intensive drug discovery for chronic inflammation.

Hospitalization after hydroxychloroquine initiation in patients with heart failure with preserved ejection fraction and autoimmune disease.

Hydroxychloroquine (HCQ) reduces cardiovascular events among patients with autoimmune disorders and is being evaluated as a therapeutic option for populations with high-risk cardiovascular disease. However, recent studies have raised concerns about HCQ use and cardiovascular events. To assess the association of HCQ initiation with heart failure-related and all-cause hospitalizations among patients with heart failure and preserved ejection fraction (HFpEF). We conducted a cohort study of patients aged ≥18 years with diagnosed HFpEF and autoimmune disease using MarketScan Commercial and Medicare Supplemental databases (2007-2019). Patients were required to initiate HCQ after their first HFpEF diagnosis (HCQ users) or not (HCQ nonusers). For the patients in the HCQ users group, the first HCQ prescription date was assigned as the index date. Index date for the HCQ nonuser group was assigned by prescription-time distribution matching HCQ users, by utilizing the number of days from HFpEF diagnosis to the first HCQ prescription. After 1:≥3 propensity score (PS) matching, Cox proportional hazards regression models were used to compare HF-related and all-cause hospitalizations between users and nonusers. After PS matching, 2229 patients (592 HCQ users and 1637 HCQ nonusers) were included. After controlling for covariates, patients who received HCQ had lower risks of HF-related hospitalization (adjusted hazard ratio, 0.44; 95% CI, 0.24-0.82) and all-cause hospitalization (adjusted hazard ratio, 0.69; 95% CI, 0.57-0.83) compared with patients not using HCQ. Among patients with HFpEF and autoimmune disease, initiation of HCQ use was associated with a decreased risk of HF-related and all-cause hospitalizations.

Hypertension and Cardiovascular Outcomes in Inflammatory and Autoimmune Diseases: A Systematic Review and Meta-analysis.

This review aimed to investigate the prevalence of hypertension and cardiovascular (CV) complications in various inflammatory and autoimmune diseases (IAD). Despite recent improvements in the management of IAD, patients with IAD still have an increased CV mortality and CV complications, mostly related to CV risk factors such as hypertension and inflammation. We systematically searched MEDLINE and EMBASE libraries for controlled studies involving hypertension and CV complications in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriasis including psoriatic arthritis (PsA), Sjogren's syndrome (SS), or antineutrophil cytoplasmic antibody-associated vasculitis (AAV) between January 2000 and March 2022. We extracted data on the prevalence of hypertension and CV complications. Then, random-effects meta-analyses and exploratory multivariate meta-regression were performed to explore factors related to the prevalence of hypertension.Of 2726 studies screened, 122 were selected for the meta-analysis. The prevalence of hypertension was higher among patients with IAD than controls, with an overall unadjusted odds ratio (OR) [95% confidence interval] of 1.67 [1.58-1.76] and an adjusted OR of 1.36 [1.24-1.50]. All diseases were found to be associated with increased risk of hypertension: SLE, adjusted OR 3.40 [1.93-6.00]; psoriasis, OR 1.32 [1.16-1.51]; PsA, OR 1.49 [1.15-1.94]; RA, OR 1.28 [1.04-1.58]; SS, OR 2.02 [1.19-3.44]. Age and female sex were significantly associated with hypertension in patients with IAD. The risk of CV complications was increased: ischemic heart disease, adjusted OR 1.38 [1.21-1.57]; cerebrovascular disease, OR 1.37 [1.03-1.81]; heart failure, OR 1.28 [1.05-1.55]; atherosclerotic plaques presence, OR 2.46 [1.84-3.29].The prevalence of hypertension and CV complications is higher among patients with IAD. Screening and management of hypertension appears to be of paramount importance in these patients.

Characterization of anti-EBNA-1 antibodies and exploration of their molecular mimicry potential in an EBV-infected Sjögren's syndrome patient

There is a potential link between autoimmune diseases and Epstein-Barr virus (EBV) infections, with EBV playing a substantial role in the onset of Sjögren's syndrome (SjS). Some EBV proteins could mimic host self-antigens post-infection, leading to molecular mimicry. This similarity may cause the immune system to attack its tissues mistakenly. Among the various proteins associated with EBV, nuclear antigen 1 (EBNA-1) is essential for the latent replication of infected cells and is prevalent in all EBV-related diseases. In the study, single-chain variable fragment (scFv) antibodies targeting EBNA-1 were isolated using phage display technology from a primary SjS patient who also had a chronic active EBV infection. The specific clones were enriched after panning, and the binding activity of selected scFvs targeting EBNA-1 was confirmed. Sequence analysis indicated that the scFvs exhibiting positive signals could be grouped into five clones, all of which used homologous heavy chain V regions derived from germline Vh4-39, and two types of light chain V regions stemming from germline Vλ1-44 and Vλ3-15. These scFvs were found to exhibit a high degree of somatic mutations, likely indicative of antigen selection. Of the scFvs, P1-3 demonstrated the strongest binding affinity to EBNA-1, exhibiting a determined value of 7.3 x 10-8 M, and showed cross-reactivity to the SjS associated La/SSB self-antigen. The experimental results combined with AlphaFold 3 predictions revealed a potential epitope for scFv P1-3 binding to EBNA-1. Additionally, scFv P1-3 could also cross-bind to the modeled structure of La/SSB. We inferred a possible structural correlation between EBNA-1 and La/SSB involving an X2AX6PG epitope motif. This research contributes to our understanding of the structural basis of the interactions between antibodies and EBNA-1, shedding light on the VH and VL gene usage of anti-EBNA-1 antibodies in EBV-infected SjS patients and the potential origins of autoantibodies.

Vitiligo is associated with an increased risk of cardiovascular diseases: a large-scale, propensity-matched, US-based retrospective study

Vitiligo is an autoimmune disease, characterized by specific destruction of melanocytes. While associations with numerous comorbid conditions, which potentially increase the risk of cardiovascular diseases have been described, data on the risk for cardiovascular disease is inconclusive. To address this relevant knowledge gap, this study aims to identify the risk of cardiovascular disease in vitiligo. The US Collaborative Network was accessed using the TriNetX platform, allowing retrospective data retrieval from electronic health records (EHRs) from 57 US based health care organizations (HCOs). Patients with vitiligo and controls were identified by their respective ICD10 codes. Risk of onset of several cardiovascular diseases was determined in patients within 15 years after diagnoses. A total of 94 diagnoses with a prevalence of ≥1% in both cohorts, which consisted of 96,581 individuals per group after propensity-score-matching, were identified. Of those, 54 displayed an increased risk in vitiligo. None of the cardiovascular diseases investigated were associated with a decreased risk in patients with vitiligo. Specifically, cerebral infarction occurred in 1.3% of patients with vitiligo, and 1.0% in controls. This difference translated into a hazard ratio (HR) of 1.21 (95% confidence interval [CI] 1.11-1.32, padj<0.001). Venous thromboembolism was recorded in 1.34% of cases and 1.02% of controls without vitiligo, resulting in an increased HR of 1.27 (95% CI 1.171-1.38, padj<0.001). Further, major adverse cardiovascular events (MACE) as a composite endpoint was evaluated. The risk for MACE was increased following a vitiligo diagnosis (HR 1.28, 95% CI 1.22-1.35, padj<0.001), which persisted in both sensitivity analyses. Patients with vitiligo display an increased risk of onset of cardiovascular diseases as compared to healthy individuals. Thus, vitiligo might require more precise monitoring and systemic treatment. This research was supported by the Schleswig-Holstein Excellence-Chair Program from the State of Schleswig Holstein, by the Excellence Cluster Precision Medicine in Chronic Inflammation (DFG, EXC 2167), and by DFG Individual Grant LU 877/25-1.

PEGylated lipid polymeric nanoparticles for management of rheumatoid arthritis

PEGylation, an extensively used surface modification method for nanoparticles (NPs), continues to hold promise for optimizing therapy for various medical conditions by achieving efficient and selective delivery of multiple therapeutics and nanocarriers. Rheumatoid arthritis is a chronic autoimmune and inflammatory disease treated mainly by disease-modifying antirheumatic drugs (DMARDs) (e.g., leflunomide); however, these drugs suffer from systemic exposure and adverse effects. Leflunomide (LEF) was loaded into PEGylated (PEG)-lecithin chitosan nanoparticles (LCNPs) to enhance its therapeutic efficacy and safety profile. LEF-PEG-LCNPs showed a particle size of 115.31 ±3.24 nm, a zeta potential of 31.3±1.8 mV, an entrapment efficiency of 89.63 ±2.25 %, and an improved release profile than non-pegylated LCNPs and LEF-pure. Fourier transform-infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and transmission electron microscopy (TEM) were also performed. The effects of orally administrated LEF-pure, LEF-marketed, LEF-LCNPs and LEF-PEG-LCNPs against Complete Freund’s Adjuvant (CFA)-induced rheumatoid arthritis (RA) in rats were investigated. LEF-PEG-LCNPs showed more significant inhibition of paw edema (72.74%), rheumatoid factor RF (40.76%), TNF-α (55.6%), IL-6 (47.42%), ALT (80.59%), and AST (39.83%) as compared to positive control. Furthermore, histopathological studies showed a nearly normal appearance of bone trabecular tissue, liver, kidney, lung, and heart. This highlights LEF-PEG-LCNPs as an exceptional anti-rheumatoid arthritis therapy compared to pure and marketed formulations.

AIPs-DeepEnC-GA: Predicting Anti-inflammatory Peptides using Embedded Evolutionary and Sequential Feature Integration with Genetic Algorithm based Deep Ensemble Model

Inflammation is a biological response to harmful stimuli including infections, damaged cells, tissue injuries, and toxic chemicals. It plays an essential role in facilitating tissue repair by eliminating pathogenic microorganisms. Currently, numerous therapies are applied to treat autoimmune and inflammatory diseases. However, these conventional anti-inflammatory medications are often labor-intensive, costly, and associated with adverse side effects. Recently, researchers have identified anti-inflammatory peptides (AIPs) as a cost-effective alternative for treating several inflammatory diseases, due to their high selectivity for target cells with minimal side effects. In this study, we introduce a novel computational predictor, AIPs-DeepEnC-GA, developed to accurately predict AIP samples. The training sequences are encoded using a novel n-spaced dipeptide-based position-specific scoring matrix (NsDP-PSSM) and Pseudo position-specific scoring matrix (PsePSSM)-based embedded evolutionary features. Additionally, the reduced- amino acid alphabet (RAAA-11), and composite Physiochemical properties (CPP) are employed to capture cluster-physiochemical properties based on structural information. A hybrid feature strategy is then applied, integrating embedded evolutionary features, CPP and RAAA-11 descriptors to overcome the limitations of individual encoding methods. Minimum redundancy and maximum relevance (mRMR) is utilized to select the optimal features. The selected features are trained using four different deep-learning models. The predictive labels generated by these models are provided to a genetic algorithm to form a deep-ensemble training model. The proposed AIPs-DeepEnC-GA model achieved a ∼15% increase in predictive accuracy, reaching 94.39%, and a 19% improvement in the area under the curve (AUC), achieving a value of 0.98 using training sequences. For independent datasets, our method obtained improved accuracies of 91.87%, and 89.21%, with AUC values of 0.94 and 0.92 for Ind-I, and Ind-II, respectively. Our proposed AIPs-DeepEnC-GA model demonstrates an 11% improvement in predictive accuracy over existing AIPs computational models using training samples. The efficacy and reliability of this model make it a promising tool for both in drug development and research academia.

Metformin (The Miracle Drug) Kinetics in Different Diseases such as Cancer

: Metformin, a miracle drug that was introduced a century ago, could be considered for various aspects of diseases such as diabetes (type 1 and 2), cancer prevention or chemotherapy, metabolic and neurodegenerative disease. It is well known that the frequency of cancer is higher in patients with type 2 diabetes mellitus. This review aims to provide updated information regarding clinical pharmacokinetics and the mechanism of action of Metformin in different diseases such as cancer. Diabetes type 1 is another chronic autoimmune disease detected usually in early childhood due to immune-mediated devastation of insulin-producing pancreatic beta-cells. Because of the lack of effective therapeutic approaches, its prevalence is increasing. Regarding cancer, an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths were reported in 2020 worldwide. By 50-60% bioavailability, the main route of metformin excretion is through urine. Its mechanism of action is based on 1) initiation of adenosine monophosphate-activated kinase, 2) block proinflammatory paths in perivascular adipose tissue, 3) decrease in monocyte-to-macrophage differentiation in vascular tissues, and 4) improvement in endothelial function. Metformin induces adenosine monophosphate-activated protein kinase signaling and suppresses gluconeogenesis. Antitumor properties of Metformin include a decrease in reactive oxygen species generation and inducing autophagy. In addition to glucose-lowering effects, Metformin has moderate anti-inflammatory and antioxidative effects. It could improve lipid profile and reduce overweight individuals' body mass and arterial blood pressure. In type 1 diabetes, Metformin reduces the requirement for daily insulin and improves glycemia. Its long-term use decreases cardiovascular events. In addition to inhibiting the synthesis of lipids via a reduction in oxidative stress, Metformin inhibits inflammation and increases energy metabolism. Finally, by reducing micro- and macro-vascular consequences, mortality-related diabetes and cancer decline by metformin administration. Therefore, in addition to diabetes, Metformin could reduce the proliferation of cancer cells and the possibility of malignancies in different types of cancer.

Hyaluronic acid modified prussian blue analogs/TiO₂ janus nanostructures through efficient charge separation to enhance photocatalytic-driven dual gas for achieve multimodal treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the abnormal proliferation of fibroblast-like synoviocytes and changes in the joint synovium, including elevated reactive oxygen species, decreased pH, and reduced oxygen content. In this study, we synthesized a novel nanocomposite material, namely HA-PBA-TiO2 Janus nanocomposite, by in situ etching in prussian blue analogs doped with Co and Ni, followed by the growth of TiO2 nano-flowers and encapsulation in hyaluronic acid. When these janus nanoparticles diffused to the inflammatory sites of RA, they exhibited outstanding photocatalytic water-splitting ability under 660 nm laser irradiation, generating H2 and O2. This capability helps ameliorate the hypoxic microenvironment at RA inflammatory sites by eliminating reactive oxygen species (ROS) and enhancing antioxidation and oxygenation. Furthermore, owing to the doping of Co and Ni, HA-PBA-TiO2 exhibits photothermal conversion capability, which significant damage to FLS upon exposure to 660 nm laser irradiation, thereby controlling their aberrant proliferation. Through a series of in vitro and in vivo experiments, we validated the significant therapeutic efficacy of HA-PBA-TiO2 in treating RA, highlighting its broad prospects for application.

IGLON5 Frequency in Idiopathic REM Sleep Behavior Disorder: A Multicenter Study.

Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD. Participants were enrolled in the North American Prodromal Synucleinopathy cohort with polysomnography-confirmed iRBD, free of parkinsonism and dementia. Plasma samples were systematically screened for the autoantibodies IGLON5, DPPX, LGI1, and CASPR2 using plasma IgG cell-based assay. Positive or equivocal results were confirmed by repeat testing, plus tissue-based indirect immunofluorescence assay for IGLON5. Of 339 samples analyzed, 3 participants (0.9%) had confirmed positive IGLON5 autoantibodies in the cell-based assay, which were confirmed by the tissue-based assay. An additional participant was positive for CASPR2 with low titer by cell-based assay only (of lower clinical certainty). These cases exhibited a variety of symptoms including dream enactment, cognitive decline, autonomic dysfunction, and motor symptoms. In 1 IGLON5 case and the CASPR2 case, evolution was suggestive of typical synucleinopathy, suggesting the possibility that findings were incidental. However, 2 participants with IGLON5 died before diagnosis was clinically suspected, with a final clinical picture highly suggestive of autoimmune disease. Our finding that nearly 1% of a large iRBD cohort may have a serious but potentially treatable autoantibody syndrome has important clinical implications. In particular, it raises the question of whether autoantibody testing for IGLON-5-IgG should be widely implemented for participants with iRBD, considering the difficulty in diagnosis of autoimmune diseases, their response to treatment, and the potential for rapid disease progression. However, any routine testing protocol will also have to consider costs and potential adverse effects of false-positive findings. NCT03623672.

Optic Neuritis and its Prevalence in Immunocompromised Patients: A Review Article

Optic neuritis is an inflammation that affects the optic nerve, causing vision loss, eye pain, and changes in color perception. The condition can be associated with autoimmune diseases such as multiple sclerosis (MS) or infections, especially in immunocompromised individuals such as HIV/AIDS patients or those undergoing chemotherapy. In these individuals, optic neuritis usually results from opportunistic infections like toxoplasmosis and syphilis, complicating diagnosis and treatment. In immunocompetent patients, optic neuritis may indicate autoimmune diseases like MS or neuromyelitis optica (NMO), with better prognoses when treated early with corticosteroids. However, in immunocompromised individuals, the prognosis tends to be worse due to underlying infections and a limited response to immunosuppressive treatment. The management of optic neuritis involves anti-inflammatory therapies and, in cases of infections, specific antimicrobials. Continuous clinical and visual follow-up is also crucial. Studies suggest that clinical outcomes vary depending on the etiology and the patient's immune status, highlighting the need for personalized therapeutic strategies. Early diagnosis is critical to improving vision and quality of life for patients.

The Role of Gut Microbioma in Human Health: Exploring the Impact on Metabolism, Immunity, and Neurological Disorders

Abstract: The human microbiota has been progressively accepted for its role in sustaining overall health and well-being. The gut microflora vigorously communicates with the host metabolic system that exert influence on the progression, maturation, immune cells development and immune homeostasis maintenance. For the proper functioning of the immune system a diversified and steady gut microflora is needed, while “Dysbiosis” or an imbalance in the gut microbioma will lead to autoimmune and inflammatory diseases. The gut microbiota provides shape to our immune response and contribute to host protection against pathogen or bacterium through mechanisms such as the transformation of pro- inflammatory cytokine production, regulatory T-cell inductor and by intestinal mucosaql barrier. In addition to gut microbiota can affect our neurological function and play a key role in the pathogenesis of psychological disorders such as autism, depression, anxiety, Parkinson and Alzheimer’s disease. Gut microbiota can regulate neurological disorders by supplementing them with fecal transplantation, probiotics and antibiotics. An important parameter to consider gut microbioma disorder is Firmicutes/ Bacteroidetes.

Pathogenesis of psoriatic arthritis: new insights from a bone marrow perspective.

Psoriatic arthritis is an immune-mediated disease that primarily affects the skin and joints. It falls under the umbrella term of rheumatic diseases, which describes a group of closely related yet distinct disorders with many common underlying molecular pathways. Despite the distinct clinical manifestation of each disorder, the shared therapeutic strategies attest to the commonality of cellular and molecular underpinnings. Herein we provide a concise yet comprehensive overview of the interleukin (IL)-23/IL-17 axis and its involvement in mechanistic pathways leading to the pathogenesis of this dual skin and joint clinical manifestation which is characteristic of psoriatic arthritis and other rheumatic diseases. The interconnection between activated innate immune cells and adaptive immunity has transformed current thinking to include other organs such as the bone marrow as potential tissue of disease origin. A plethora of animal models and genetic studies converge on the critical role of IL-23/IL-17 axis, and highlight the importance of myeloid cell activation as common pathways between autoinflammatory and autoimmune diseases and chronic inflammation. These findings underscore the intricate immune mechanisms involved in inflammatory arthritis and highlight molecular mechanisms in disease pathogenesis. These insights pave the way for the development of novel diagnostic and therapeutic strategies, with a focus on translating these findings into improved clinical practice.

Associations vulvar lichen sclerosus with autoimmune thyroid diseases.

Vulvar lichen sclerosus (VLS) is defined as a chronic inflammatory skin disease that most often involves lesions on the mucous membranes of the vulva with a tendency to progress to the anal skin. The etiopathogenesis of VLS remains unknown and is likely multifactorial. Data emphasize the role of immunological factors - more than 25% of VLS cases coexist with autoimmune diseases. The purpose of the present study was to determine the correlation of the prevalence of anti-thyroid antibodies - IgG class antibodies against thyroid peroxidase and IgG class antibodies against thyroglobulin in women with vulvar lichen sclerosus, and the appropriateness of screening tests for autoimmune thyroid diseases in women with vulvar lichen sclerosus. Fifty women with vulvar lichen sclerosus were enrolled in the study. The control group consisted of 41 healthy women. A detailed medical history was taken with all patients, followed by laboratory determinations - anti-thyroid antibodies - IgG class antibodies against thyroid peroxidase and IgG class antibodies against thyroglobulin. Antibodies to thyroid peroxidase were present in 12% of the study group with vulvar lichen sclerosus and 4.88% of the control group, and this difference was not statistically significant (p = 0.41). Anti-thyroglobulin antibodies were detected in 4% of the patients with vulvar lichen sclerosus and 4.88% of the control group, and this difference was not statistically significant either (p = 0.76). The study did not confirm the association of VLS with autoimmune thyroid diseases. Undoubtedly, based on the data available in the literature, further studies are needed to determine the mechanisms behind the association between vulvar lichen sclerosus and autoimmune thyroid diseases.

Discovery and Total Synthesis of Anhydrotuberosin as a STING Antagonist for Treating Autoimmune Diseases

Excessive activation of the stimulator of the interferon gene (STING) pathway has been identified as a significant contributor to various autoimmune diseases, such as STING‐associated vasculopathy with infantile‐onset (SAVI) and inflammatory bowel disease (IBD). However, discovering effective STING antagonists for treating STING‐mediated autoimmune disorders remains challenging. Herein, we identified the natural product anhydrotuberosin (ATS) as a potent STING antagonist by a high‐throughput chemical screen and follow‐up biological validations. However, the limited supply from natural product isolation impeded the pharmacological evaluations of ATS. Accordingly, we developed a concise and scalable total synthesis of ATS in 6 steps. Enabled by total synthesis, we further extensively investigated ATS’s mode of action and evaluated its therapeutic potential. Remarkably, ATS inhibits STING signaling in PBMCs derived from three SAVI patients. ATS showed decent pharmacokinetic parameters and strongly alleviated tissue inflammation in DSS‐induced IBD colitis and Trex1‐/‐ autoimmune animal models with low toxicity. Collectively, this research lays the foundation for developing novel STING antagonists as an effective therapy for autoinflammatory and autoimmune diseases.

Low-dose aspirin improves blood perfusion of obstetric anticardiolipin syndrome in China.

This study evaluates the endometrial receptivity of obstetric anticardiolipin syndrome (OAPS) patients using various ultrasound indicators and the efficacy of low-dose aspirin (LDA) treatment. This retrospective study recruited patients from Shanghai Ren Ji Hospital, China from January 2022 to December 2023. Doppler parameters of the endometrium and uterine artery blood flow were recorded to assess the endometrial receptivity of OAPS patients compared with normal pregnant women and an other immune diseases group. The receiver operating characteristic curve was used to predict the risk of OAPS patients. Doppler parameters of OAPS patients were conducted repeatedly after a 2-month period of treatment with LDA. Compared with normal pregnant women, the OAPS group showed remarkably increased endometrial perfusion resistance (PI, RI, S/D) and uterine artery perfusion resistance (RI and S/D) (P < 0.001) and had good predictive values (area under the curve = 0.806, 0.976, 0.942, 0.902, and 0.901, respectively). The endometrial thickness of the OAPS group was much thinner than that of the normal group (P < 0.001). Uterine blood flow impedance PI showed no difference in both groups (P = 0.68). In comparison to other autoimmune diseases, the OAPS group also showed an increasing trend in the resistance of endometrium and uterine artery blood flow. After LDA treatment, there was an obvious improvement in the endometrial blood flow perfusion in the OAPS group (P < 0.01). Compared with the normal group and other autoimmune diseases, the resistance of endometrial and uterine artery blood flow in the OAPS group was increased significantly. The Doppler index showed the predictive value of OAPS, and it was confirmed that LDA could enhance blood perfusion among OAPS women.

Association between vulvar lichen sclerosus and celiac disease in woman.

Vulvar lichen sclerosus (VLS) is a chronic inflammatory condition involving mainly the genital area with an undetermined aetiology. Recent studies show that in up to 34% of cases in adult women, VLS coexists with allergies or autoimmune diseases like celiac disease (CD), among others. However, literature data relating strictly to the co-occurrence of celiac disease and Duhring's disease (DH) in patients with VLS are very limited. In our study, we sought to clarify the possible relationship between vulvar lichen sclerosus in adult women and celiac disease in its cutaneous form. The aim of the study was to demonstrate the presence of celiac disease-specific antibodies in women with VLS. The control group consisted of 41 healthy women, and the study group consisted of 50 women aged 24-83 years with diagnosed vulvar lichen sclerosus who were hospitalized in the Department of Gynaecology, Obstetrics and Gynaecologic Oncology of the Bonifraters Medical Centre in Katowice. There were no significant differences in blood serum levels of CD-specific antibodies between both groups. The study conducted did not confirm the association between vulvar lichen sclerosus and celiac disease or Duhring's disease. The main limitation of the research was the small size of the study and control groups. Further studies on a larger group of patients are needed. They could clarify the possible mechanisms behind the co-occurrence of these two conditions. Earlier diagnostic will help prevent the development of severe and irreversible complications.

Reactive arthritis in connective tissue diseases; one should be vigilant for joint tuberculosis.

The incidence of tuberculosis (TB) is increasing worldwide. Bone and joint TB are the most common types of extra-pulmonary TB, but can easily be misdiagnosed, since articular TB commonly mimics other joint diseases, including reactive and degenerative arthritis, and articular manifestations associated with systemic autoimmune diseases. Furthermore, patients with systemic auto-immune diseases are often more prone to mycobacterial infection. The diagnosis of joint TB can be made using a combination of the following methods: clinical evaluation, imaging, tuberculin skin test, interferon-gamma release assays, nucleic acid amplification tests, and Gene X-pert MTB/rifampicin assay.

The Type 1 Diabetes T Cell Receptor and B Cell Receptor Repository in the AIRR Data Commons: a practical guide for access, use and contributions through the Type 1 Diabetes AIRR Consortium.

Human molecular genetics has brought incredible insights into the variants that confer risk for the development of tissue-specific autoimmune diseases, including type 1 diabetes. The hallmark cell-mediated immune destruction that is characteristic of type 1 diabetes is closely linked with risk conferred by the HLA class II gene locus, in combination with a broad array of additional candidate genes influencing islet-resident beta cells within the pancreas, as well as function, phenotype and trafficking of immune cells to tissues. In addition to the well-studied germline SNP variants, there are critical contributions conferred by T cell receptor (TCR) and B cell receptor (BCR) genes that undergo somatic recombination to yield the Adaptive Immune Receptor Repertoire (AIRR) responsible for autoimmunity in type 1 diabetes. We therefore created the T1D TCR/BCR Repository (The Type 1 Diabetes T Cell Receptor and B Cell Receptor Repository) to study these highly variable and dynamic gene rearrangements. In addition to processed TCR and BCR sequences, the T1D TCR/BCR Repository includes detailed metadata (e.g. participant demographics, disease-associated parameters and tissue type). We introduce the Type 1 Diabetes AIRR Consortium goals and outline methods to use and deposit data to this comprehensive repository. Our ultimate goal is to facilitate research community access to rich, carefully annotated immune AIRR datasets to enable new scientific inquiry and insight into the natural history and pathogenesis of type 1 diabetes.

Incidence and risk of autoimmune disease in patients with a previous diagnosis of myocarditis - a nationwide Danish register-based cohort study

Abstract Introduction Myocarditis is a severe condition with an acute onset characterized by myocardial inflammation. The aetiology is heterogenous ranging from viral infections to autoimmune diseases (AD). However, it is currently unknown if patients with a first-time diagnosis of myocarditis are at higher risk of developing an autoimmune disease (AD) at a later stage. Purpose To estimate the risk of developing AD in patients with a first-time diagnosis of myocarditis during 20 years of follow-up. Methods Data source and study design: Nationwide register-based cohort study using data from Danish national administrative registers containing data on ICD-10 codes of diagnoses, prescription of pharmaceuticals, as well as date of birth and death on all Danish citizens. Study population: All Danish patients with a diagnosis of myocarditis from 2002-2020. Patients with previous diagnosis of AD were excluded. A control population without a diagnosis of myocarditis nor AD was sex and aged matched 1:5. Endpoints: Receiving a diagnosis of AD out of 35 recognized AD, and all-cause mortality. Statistics: Cumulative incidence of AD diagnosis was calculated by use of Aalen-Johansen estimation and all-cause mortality rate by Kaplan-Meier estimation. Hazard ratio (HR) by multivariate Cox regression modelling, standardized to sex, age, and comorbidities. Standardized relative (RR) and absolute (AR) risk derived from Cox regression by estimated Average Treatment Effect. Continuous variables are presented as median [1st quartile, 3rd quartile]. Results Study population: Myocarditis cohort: n=2,684. Control cohort: n=13,420. Median follow-up time: 9.5 years [5.4, 14.6]. Median age: 46 years [28, 67]. 69.5 % were of male sex. Comorbidities including hypertension, heart failure, and ischemic heart disease were significantly more common in patients with myocarditis. Autoimmune disease: At 20 years of follow-up, the cumulative incidence of AD diagnosis was 14.1% in the myocarditis cohort, and 5.8% in the control cohort. Adjusted HR for AD diagnosis in myocarditis vs. control cohorts was 2.65 (95% CI 2.19-3.17). Adjusted RR at 1 and 20 years of follow-up was 2.26 (95% CI 2.13-3.11) and 2.47 (95% CI 2.03-2.90), respectively. Figure 1 (left) shows AR of developing an AD at 20 years of follow-up, stratified by sex and age group. Mortality: Kaplan-Meier all-cause mortality was 40.5% in the myocarditis cohort, and 28.5% in the control cohort. Adjusted HR: 1.84 (95% CI 1.67-2.03). Adjusted RR at 1 and 20 years of follow-up: 1.77 (95% CI 1.60-1.93) and 1.31 (95% CI 1.25-1.36), respectively. Figure 1 (right) shows stratified AR of all-cause mortality at 20 years of follow-up. Conclusions Patients with a diagnosis of myocarditis had a significantly higher risk of developing AD in addition to significantly higher all-cause mortality compared to patients without previous myocarditis diagnosis. These findings suggest underlying and subsequent AD should be considered in patients with myocarditis.20-year AR of AD and all-cause mortalityICD-10 codes of AD investigated