Onset Of Autoimmune Diseases Research Articles

Denervation-Induced Sarcopenia Model.

Rheumatoid arthritis (RA) is an important risk factor for sarcopenia. Physical inactivity, systemic inflammatory factors, and medication directly or indirectly induce skeletal muscle loss in RA patients. The sarcopenia-induced systemic or local proinflammatory microenvironment also contributes to the onset and progression of autoimmune disease. Accumulated evidence suggests the importance of treatment and management of sarcopenia in patients with RA to improve their long-term prognosis. To elucidate the relationship between skeletal muscle and systemic immune homeostasis, a denervation-induced skeletal muscle-losing mouse model is introduced in this chapter. By developing local amyotrophy in the sciatic nerve-dominant area in a RA model, the underlying mechanism of sarcopenia in RA could be assessed. Also, an examination of the efficacy of anti-rheumatic regents on sarcopenia and the influence of sarcopenia management on RA improvement is also achievable.

Identification of Biomarker IL2Rβ in Ankylosing Spondylitis via Multi-Chip Integration Analysis of Gene Differential Expression.

Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease that affects axial joints such as the spine. Early diagnosis is essential to improve treatment outcomes. The purpose of this study is to uncover underlying genetic diagnostic features of AS. We downloaded gene expression data from the Gene Expression Omnibus (GEO) database for three studies of groups of healthy and AS samples. After preprocessing and normalizing the data, we employed linear models to identify significant differentially expressed genes (DEGs) and further integrated the differential genes to acquire reliable differential transcriptional markers. Gene functional enrichment analysis was conducted to obtain enriched pathways and regulatory gene interactions were extracted from pathways to further elucidate pathway networks. Seventy-three reliably differentially expressed genes (DEGs) were integrated by differential analysis. Utilizing the regulatory relationships of the 21 Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway genes that were enriched in the analysis, a regulatory network of 622 genes was constructed and its topological properties were further analyzed. Functional enrichment analysis found 73 DEGs that were strongly associated with immune pathways like Th17, Th1 and Th2 cell differentiation. Using KEGG combined with DEGs, six hub genes (KLRD1, HLA-DRB3, HLA-DRB5, IL2Rβ, CD247, and CXCL10) were suggested from the network. Of these, the IL2Rβ gene was significantly differentially expressed compared with the normal control. IL2Rβ (Interleukin-2 receptor beta) is strongly associated with the onset and progression of autoimmune joint diseases, and may be used as a potential biomarker of AS. This study offers new characteristics that can help in the diagnosis and individualized therapy of AS.

Mechanisms of Regulation Allergic and Autoimmune Reactions by Bacterial Origin Bioregulators

Relevance. The increase in allergic and autoimmune diseases observed in recent decades highlights the need for therapy and prevention, which requires detailed research into the mechanisms of their occurrence. The onset and progression of allergic and autoimmune diseases are influenced by genetic predisposition, lifestyle, environmental factors, and disruptions in the coordinated operation of the immune system, and as a consequence of immune homeostasis. Treatment of these diseases is primarily symptomatic and often accompanied by undesirable side effects. Immune system disorders in various pathologies have their own characteristics for each type of disease, and at the same time have common mechanisms. Considering the presence of a large number of various microorganisms in the human body, taking their influence into account is of paramount importance. Microorganisms are a source of biologically active molecules, the action of which can either prevent and reduce the severity of the disease or exacerbate it. The aim of this study was to analyze the cytokine profile of the effects of fragments of cell walls of Gram-negative and Gram-positive bacteria - lipopolysaccharide (LPS) and muramyl peptide (MP), as well as nisin - an antimicrobial peptide of bacterial origin on human mononuclear cells. Materials and Methods. Mononuclear cells were obtained from peripheral blood of healthy volunteers using Cell separation media Lympholyte CL 5015, and were cultured in the presence of LPS, GMDP and bacteriocin nisin. The cytokine activity of LPS, GMDP and bacteriocin nisin was examined using the multiplex cytokine analysis; the analysis of surface markers was determined flow cytometry. Results and Discussion. It was shown that bacterial cell wall fragments to a much greater extent than nisin induce the production of cytokines, chemokines, and growth factors. It was established that LPS and MP increase the expression of CD11c on dendritic cells, while bacteriocin nisin does not affect the increase of CD11c+ DCs. LPS and MP in the conducted ex vivo studies did not affect the emergence of CCR7. Conclusion. Bacterial origin bioregulators trigger a negative feedback mechanism by inducing the synthesis of anti-inflammatory factors, that can prevent the inflammatory process. Understanding the molecular mechanisms of the influence of bacterial origin bioregulators on the human body opens new approaches in the prevention and development of personalized therapy strategies.

Tregs protect against invariant NKT cell-mediated autoimmune colitis and hepatitis.

Immunomodulatory T cells play a pivotal role in protection against (auto)immune-mediated diseases that open perspectives for therapeutic modulation. However, how immune regulatory networks operate in vivo is less understood. To this end, we focused on FOXP3+CD4+CD25+ regulatory T cells (Tregs) and invariant natural killer T (iNKT) cells, two lymphocyte populations that independently regulate adaptive and innate immune responses. In vitro, a functional interplay between Tregs and iNKT cells has been described, but whether Tregs modulate the function and phenotype of iNKT cell subsets in vivo and whether this controls iNKT-mediated autoimmunity is unclear. Taking advantage of the conditional depletion of Tregs, we examined the in vivo interplay between iNKT and Treg cells in steady state and in preclinical models of liver and gut autoimmunity. Under non-inflamed conditions, Treg depletion enhanced glycolipid-mediated iNKT cell responses, with a general impact on Type 1, 2 and 17 iNKT subsets. Moreover, in vivo iNKT activation in the absence of Tregs suppressed the induction of iNKT anergy, consistent with a reduction in programmed cell death receptor 1 (PD-1) expression. Importantly, we unveiled a clear role for an in vivo Treg-iNKT crosstalk both in concanavalin A-induced acute hepatitis and oxazolone-induced colitis. Here, the absence of Tregs led to a markedly enhanced liver and gut pathology, which was not observed in iNKT-deficient mice. Taken together, these results provide evidence for a functional interplay between regulatory T cell subsets critical in controlling the onset of autoimmune disease.

T helper (Th) cell profiles and cytokines/chemokines in characterization, treatment, and monitoring of autoimmune diseases

Autoimmune diseases (AD) consist of a spectrum of disease entities whose etiologies are very complex and still not well understood. Every individual has the potential for developing AD under appropriate conditions because the body contains lymphocytes that are potentially reactive with self-antigens. The aims of this study are to (1) explore the flow cytometry method to identify the frequency of various circulating CD4+ T helper (Th) cell-subsets, including Th1, Th2, Th9, Th17, Th17.1, and Th22; (2) In parallel, to examine multiplex ELISA method for pathogenic inflammatory cytokines/chemokines, and (3) To assess the correlation of expression of T cell-subsets with serum cytokines/chemokines and understand its clinical importance with available AD treatments. We analyzed Th17, Th17.1, Th22, Th2, Th1, and Th9 Th cell populations and compared the concentrations of 67 cytokines/chemokines in healthy as well as AD-diagnosed patients. We observed that patients with autoimmune markers had significantly elevated percentages of naïve (Th17, Th22, and Th9) as well as memory (Th17 and Th22) Th cell-subsets, along with increased concentrations of cytokines/chemokines (Eotaxin, TNFβ, and FABP4). The percentage of Th cell-subsets correlated positively or negatively with the production of cytokines/chemokines of patients diagnosed with AD. Our study demonstrates that the naïve and memory Th cell-subsets with positive correlations to cytokines/chemokines show new diagnostic markers to predict the patients' outcome, while the negative correlation of cytokines/chemokines shows the response to autoimmune therapies. Our findings of Th cell-subsets by flow cytometry and cytokines/chemokines by multiplex ELISA suggest that CCR6+ Th cell-subsets (Th17, Th17.1, Th22, and Th9) contribute to our understanding of the pathogenesis of AD and identify the new onset of AD from the autoimmune spectrum. Our findings highlight the importance of CCR6+ as a possible marker in the characterization, treatment, and monitoring of AD.

Thyroid Autoimmunity and SARS-CoV-2 Infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological culprit of COronaVIrus Disease 19 (COVID-19), can enter the cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which has been found in several tissues including in endocrine organs, such as the ovaries, testes, pancreas, and thyroid. Several thyroid disorders have been associated with SARS-CoV-2 infection [subacute thyroiditis (SAT), thyrotoxicosis, and non-thyroidal illness syndrome (NTIS)] and, in part, they are believed to be secondary to the local virus replication within the gland cells. However, as documented for other viruses, SARS-CoV-2 seems to interfere with several aspects of the immune system, inducing the synthesis of autoantibodies and triggering latent or new onset autoimmune disease (AID), including autoimmune thyroid disease (AITD), such as Hashimoto Thyroiditis (HT) and Graves' disease (GD). Several mechanisms have been hypothesized to explain this induction of autoimmunity by SARS-CoV-2 infection: the immune system hyper-stimulation, the molecular mimicry between the self-antigens of the host and the virus, neutrophils extracellular traps, and finally, the virus induced transcriptional changes in the immune genes; nonetheless, more evidence is needed especially from large, long-term cohort studies involving COVID-19 patients, to establish or reject this pathogenetic relationship.

Regulating the regulatory T cells as cell therapies in autoimmunity and cancer.

Regulatory T cells (Tregs), possess a pivotal function in the maintenance of immune homeostasis. The dysregulated activity of Tregs has been associated with the onset of autoimmune diseases and cancer. Hence, Tregs are promising targets for interventions aimed at steering the immune response toward the desired path, either by augmenting the immune system to eliminate infected and cancerous cells or by dampening it to curtail the damage to self-tissues in autoimmune disorders. The activation of Tregs has been observed to have a potent immunosuppressive effect against T cells that respond to self-antigens, thus safeguarding our body against autoimmunity. Therefore, promoting Treg cell stability presents a promising strategy for preventing or managing chronic inflammation that results from various autoimmune diseases. On the other hand, Tregs have been found to be overactivated in several forms of cancer, and their role as immune response regulators with immunosuppressive properties poses a significant impediment to the successful implementation of cancer immunotherapy. However, the targeting of Tregs in a systemic manner may lead to the onset of severe inflammation and autoimmune toxicity. It is imperative to develop more selective methods for targeting the function of Tregs in tumors. In this review, our objective is to elucidate the function of Tregs in tumors and autoimmunity while also delving into numerous therapeutic strategies for reprogramming their function. Our focus is on reprogramming Tregs in a highly activated phenotype driven by the activation of key surface receptors and metabolic reprogramming. Furthermore, we examine Treg-based therapies in autoimmunity, with a specific emphasis on Chimeric Antigen Receptor (CAR)-Treg therapy and T-cell receptor (TCR)-Treg therapy. Finally, we discuss key challenges and the future steps in reprogramming Tregs that could lead to the development of novel and effective cancer immunotherapies.

A Comprehensive Review of 16 Existing Reviews that Investigate the Influence of Stress on the Onset and Exacerbation of Autoimmune Diseases

A Comprehensive Review of 16 Existing Reviews that Investigate the Influence of Stress on the Onset and Exacerbation of Autoimmune Diseases

Network Pharmacology-based Analysis to Investigate Bioactive from the Root of Astragalus membranaceus against Immunomodulatory Protein and their Role in Autoimmune Thyroiditis (AIT)

Background The thyroid is the prime organ of infection during the onset of autoimmune disease. The disease is known as Autoimmune thyroiditis (AIT). In recent times, AIT has been alarming worldwide, with growing attention towards pharmaceutical companies for finding new drugs for therapy. The present investigation aims to use a multi-targeting approach to identify the best compound from the root of Astragalus membranaceus for synergistic therapy of AIT. Materials and Methods To explore the mechanism of action of the compounds, the present study uses network pharmacology-based methods. Totally, 48 genes involved in AIT were collected from the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG). Gene ontology (GO) annotation, disease ontology, and pathway enrichment analysis were conducted. The chemical structure of the compounds from A. membranaceus was retrieved from the PubChem database. To study the toxic and pharmacological efficiency of the chemical structure, absorption, distribution, metabolism, excretion, and toxicity (ADMET) screening was performed. Results The ononin and astroside were identified as suitable with all the pharmacokinetic properties can be employed to identify the disease targets. The intersection between the compound target (C-T-N) and the AIT-related genes was identified. Totally 16 genes among the C-T networks of ononin and astroside have shown interaction with thyroid disease-related pathways and signaling pathways. Consequently, the overlapping genes between the C-T network and AIT-related genes were determined as IL2. However, from the pathway enrichment, AIT-related genes have been involved in several viral infection pathways. The genes involved in infection pathways are also targeted by ononin and astroside. Conclusion The underlying mechanism of action of the compounds on AIT-related pathways was also determined. Therefore, a network pharmacology-based strategy will provide new insight into AIT therapy. However, further studies are required to validate the investigation that can prove bioactive as a promising candidate for the treatment of AIT.

Factors associated with intention for revaccination among patients with adverse events following immunization

ObjectivesIndividuals and healthcare providers may be uncertain about the safety of revaccination after an adverse event following immunization (AEFI). We identified factors associated with physician recommendation for revaccination and participant intention to be revaccinated among patients with adverse events following immunization (AEFIs) assessed in the Canadian Special Immunization Clinic (SIC) Network from 2013 to 2019. MethodsThis prospective observational study included patients assessed in the Canadian Special Immunization Clinic Network from 2013 to 2019 for an AEFI who required additional doses of the vaccine temporally associated with their AEFI. Participants underwent standardized assessment and data collection. Physician recommendations regarding revaccination and participant intent for revaccination were recorded. AEFI impact on daily activities and need for medical attention was captured as low, moderate, high impact and serious (e.g., requiring hospitalization). Multivariable logistic regression analysis identified factors associated with physician recommendation and participant intention for revaccination, controlling for province of assessment. ResultsPhysician recommendation was significantly associated with the type of AEFI and AEFI impact. Compared to large local reaction, physician recommendation for revaccination was reduced for immediate hypersensitivity (aOR: 0.24 [95% CI: 0.08–0.76]) and new onset autoimmune disease (aOR: 0.16; 95% CI: 0.04–0.69). Compared to low impact AEFIs, physician recommendation was reduced for moderate (aOR: 0.22 [95% CI: 0.07–0.65]), high impact (aOR: 0.08 [95% CI: 0.02–0.30]), and serious AEFIs (aOR: 0.11 [95% CI: 0.03–0.37]). Participant intention for revaccination was significantly associated with AEFI impact, with reduced odds for high versus low impact AEFIs (aOR: 0.12 [95% CI: 0.04–0.42]). ConclusionPhysicians appear to use AEFI type and impact to guide recommendations while patients use primarily AEFI impact to form intentions for revaccination. The findings may help inform counselling for patients with AEFIs.

Evaluation of autoantibody profile in healthy subjects after mRNA vaccination against COVID-19.

SARS-CoV-2 severe acute respiratory syndrome has rapidly spread worldwide since 2019. All scientific and technological forces have concentrated towards the formulation of vaccines to contain the disease. In less than one year (December 2020) a first messenger RNA vaccine (Comirnaty, BioNTech/Pfizer) was authorized. However, the research community has wondered about possible side effects on the immune system, given the vaccines administration in phase 4. This study aims to evaluate the mRNA vaccine impact on the development of possible positive autoantibody profile in healthcare workers without any previous underlying pathology, after first, second and booster dose of Pfizer vaccine, by determining: circulating immune complexes concentrations (CIC); anti-myeloperoxidase (MPO) and anti-proteinase 3 (PR3) autoantibodies, the presence of antinuclear antibodies (ANA) and subsequent second level tests (extractable nuclear antigen (ENA) screen, double-strand DNA, extractable nuclear antigen (ANA) profile). The subjects were divided according to anti-SARS-CoV-2 IgG RBD antibodies increasing concentrations in: Group I<10 BAU/ml (N=114); Group II>1000 BAU/ml (N=112); Group III>2500 BAU/ml (N=78). Our data show no autoreactive response changes over time in healthy subjects after vaccination. In fact, evaluation of ANA, CIC, anti-MPO, anti-PR3 and the detection of specific autoantigens, did not display significant variations. The results suggest the exclusion of a correlation between the administration of the vaccine and the possible onset of autoimmune disorders. Nevertheless, further investigations will be needed to test for any long-term side effects on an ever-growing population.

Current understanding of CTLA-4: from mechanism to autoimmune diseases.

Autoimmune diseases (ADs) are characterized by the production of autoreactive lymphocytes, immune responses to self-antigens, and inflammation in related tissues and organs. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is majorly expressed in activated T cells and works as a critical regulator in the inflammatory response. In this review, we first describe the structure, expression, and how the signaling pathways of CTLA-4 participate in reducing effector T-cell activity and enhancing the immunomodulatory ability of regulatory T (Treg) cells to reduce immune response, maintain immune homeostasis, and maintain autoimmune silence. We then focused on the correlation between CTLA-4 and different ADs and how this molecule regulates the immune activity of the diseases and inhibits the onset, progression, and pathology of various ADs. Finally, we summarized the current progress of CTLA-4 as a therapeutic target for various ADs.

Immunoassay Detects Salivary Anti-SSA/Ro-52 Autoantibodies in Seronegative Patients with Primary Sjögren's Syndrome.

The diagnostic work-up for Sjögren's syndrome is challenging and complex, including testing for serum autoantibodies to SSA/Ro and a labial salivary gland biopsy. Furthermore, the diagnosis is often delayed. In this study, we tested the hypothesis that anti-SSA/Ro autoantibodies are detectable in the saliva of patients with primary Sjögren's syndrome (pSS) because the disease affects the salivary glands, and these autoantibodies display greater discriminatory performance in saliva than in serum. SSA/Ro-52 Ags were used to develop what is, to our knowledge, a novel quantitative electrochemical-based immunoassay: the electric field-induced release and measurement (EFIRM) platform. The clinical utility was determined by measuring salivary anti-SSA/Ro-52 autoantibodies in patients with pSS and sicca (n = 34), patients without pSS with sicca (n = 35), and healthy subjects (n = 41). The statistical analysis of discrimination included the area under the receiver operating characteristic curve. Salivary anti-SSA/Ro-52 autoantibodies were measured in 94% (32 of 34) of patients with pSS with 85% (29 of 34) seropositivity. Four of the five seronegative patients with pSS had EFIRM-measurable anti-SSA/Ro-52 autoantibodies in saliva. Additionally, 60% (21 of 35) of the seronegative patients without pSS who had sicca had EFIRM-detectable SSA/Ro-52 autoantibodies in saliva, indicating the onset of autoimmune disease. Two of the 41 healthy control subjects had EFIRM-detectable SSA/Ro-52 autoantibodies in their saliva. Salivary SSA/Ro-52 autoantibodies significantly discriminated patients with pSS or patients with the initial stage of autoimmune disease from healthy subjects with an area under the receiver operating characteristic curve of 0.91. Our findings suggest that the proposed saliva SSA/Ro-52 immunoassay improves early and accurate diagnosis of seronegative patients with pSS and patients with early-onset autoimmune disease.

Evaluation of C4 Gene Copy Number in Pediatric Acute Neuropsychiatric Syndrome

Pediatric acute-onset neuropsychiatric syndrome (PANS) is an abrupt-onset neuropsychiatric disorder. PANS patients have an increased prevalence of comorbid autoimmune illness, most commonly arthritis. In addition, an estimated one-third of PANS patients present with low serum C4 protein, suggesting decreased production or increased consumption of C4 protein. To test the possibility that copy number (CN) variation contributes to risk of PANS illness, we compared mean total C4A and total C4B CN in ethnically matched subjects from PANS DNA samples and controls (192 cases and 182 controls). Longitudinal data from the Stanford PANS cohort (n = 121) were used to assess whether the time to juvenile idiopathic arthritis (JIA) or autoimmune disease (AI) onset was a function of total C4A or C4B CN. Lastly, we performed several hypothesis-generating analyses to explore the correlation between individual C4 gene variants, sex, specific genotypes, and age of PANS onset. Although the mean total C4A or C4B CN did not differ in PANS compared to controls, PANS patients with low C4B CN were at increased risk for subsequent JIA diagnosis (hazard ratio = 2.7, p value = 0.004). We also observed a possible increase in risk for AI in PANS patients and a possible correlation between lower C4B and PANS age of onset. An association between rheumatoid arthritis and low C4B CN has been reported previously. However, patients with PANS develop different types of JIA: enthesitis-related arthritis, spondyloarthritis, and psoriatic arthritis. This suggests that C4B plays a role that spans these arthritis types.

Incident autoimmune diseases in association with SARS-CoV-2 infection: a matched cohort study.

To investigate whether the risk of developing an incident autoimmune disease is increased in patients with prior COVID-19 disease compared to those without COVID-19, a large cohort study was conducted. A cohort was selected from German routine health care data. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through December 31, 2020. Patients were matched 1:3 to control patients without COVID-19. Both groups were followed up until June 30, 2021. We used the four quarters preceding the index date until the end of follow-up to analyze the onset of autoimmune diseases during the post-acute period. Incidence rates (IR) per 1000 person-years were calculated for each outcome and patient group. Poisson models were deployed to estimate the incidence rate ratios (IRRs) of developing an autoimmune disease conditional on a preceding diagnosis of COVID-19. In total, 641,704 patients with COVID-19 were included. Comparing the incidence rates in the COVID-19 (IR=15.05, 95% CI: 14.69-15.42) and matched control groups (IR=10.55, 95% CI: 10.25-10.86), we found a 42.63% higher likelihood of acquiring autoimmunity for patients who had suffered from COVID-19. This estimate was similar for common autoimmune diseases, such as Hashimoto thyroiditis, rheumatoid arthritis, or Sjögren syndrome. The highest IRR was observed for autoimmune diseases of the vasculitis group. Patients with a more severe course of COVID-19 were at a greater risk for incident autoimmune disease. SARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection. Key Points • In the 3 to 15 months after acute infection, patients who had suffered from COVID-19 had a 43% (95% CI: 37-48%) higher likelihood of developing a first-onset autoimmune disease, meaning an absolute increase in incidence of 4.50 per 1000 person-years over the control group. • COVID-19 showed the strongest association with vascular autoimmune diseases.

REAL WORLD AND MENDELIAN RANDOMIZATION ANALYSES OF THE IMPACT OF AUTOIMMUNE DISEASE ON CLINICAL CHARACTERISTICS IN LYMPHOMA

Background: Previous studies have shown associations between the risk of lymphoma and autoimmune diseases (AIDs). Mendelian randomization (MR) can estimate causal effects of a modifiable exposure on outcomes. Herein, we estimated causal effects of AID on lymphoma using MR and analyzed clinical signatures in patients of AID-associated lymphoma. Methods: A two-sample MR framework was conducted to estimate the causal effect of genetic liability for AID on lymphoma. We enrolled in patients with a history for at least one year of AID, who diagnosed with lymphoma at Shandong Provincial Hospital. For each lymphoma case, 1 lymphoma-free AID individual was identified as a control. Measures of relative risk were calculated using conditional logistic regression. Results: Strong evidence of a potential causal effect of AID on the risk of lymphoma was found (p = 0.040). Slopes of MR regressions and causal estimates associated with each SNP are illustrated (Figure 1). In the examination of the association between single autoimmune disease and lymphoma, the only potential causal effect of Sjögren syndrome (SS) was detected (p < 0.01). There was no heterogeneity, and these effects were robust to various MR assumptions. 55 cases of lymphoma were collected and matched to 110 controls randomly selected. The number of patients according to AID lymphoma subtypes were described using heatmap (Figure 2). The median age at AID was 60 years, and the median lymphoma-diagnosing age was 40 years. The clinical course from AID to lymphoma varies considerably, with a median time of 10 years. There was a female predominance (n = 29, 52.7%). Cases with a history of rheumatoid arthritis (RA) accounted for 32.73% (n = 18), followed by psoriasis (PsO) (n = 9). Baseline characteristics of patients and controls did not significantly differ in sex, age at AID onset, age of matching time or duration of AID. Cohorts as generated by the matching process were balanced. The most represented subtype was NHL (n = 45), of which 15 were DLBCL. Among those patients, 7 were GCB type and 1 was non-GCB type. According to incomplete IHC results, 23/28 patients expressed CD20. Ki67 index of 15 patients was greater than or equal to 60%. Median follow-up for surviving patients was 49.5 months. The 1-, 3-, and 5-year OS rates were 72.5%, 45%, and 22.5%, respectively. On univariate analysis, factors including sex, type of AID, age at AID/lymphoma and disease duration were not related to lymphoma risk. The assessment of ORs for the history of RA and PsO revealed no significantly increased risks for lymphoma (OR 1.027 for RA, 1.022 for PsO). Keyword: aggressive B-cell non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

Association between air pollution exposure and outpatient visits for dermatomyositis in a humid subtropical region of China: a time-series study.

In recent years, a growing number of studies have found that air pollution plays critical roles in the onset and development of autoimmune diseases, but few studies have shown an association between air pollutants and dermatomyositis (DM). We sought to investigate the relationship between short-term exposure to air pollution and outpatient visits for DM and to quantify the burden of DM due to exposure to air pollutants in Hefei, China. Daily records of hospital outpatient visits for DM, air pollutants and meteorological factors data in Hefei from January 1, 2018 to December 31, 2021 were obtained. We used a distributed lag non-linear model (DLNM) in conjunction with a generalized linear model (GLM) to explore the association between air pollution and outpatient visits for DM, and conducted stratified analyses by gender, age and season. Moreover, we used attributable fraction (AF) and attributable number (AN) to reflect the burden of disease. A total of 4028 DM clinic visits were recorded during this period. High concentration nitrogen dioxide (NO2) exposure was associated with increased risk of DM outpatient visits (relative risk (RR) 1.063, 95% confidence interval (CI) 1.015-1.114, lag 0-5). Intriguingly, exposure to high concentration ozone (O3) was associated with reduced risk of outpatient visits for DM (RR 0.974, 95% CI 0. 0.954-0.993, lag 0-6). The results of stratified analyses showed that the cold season (vs. warm season) were more susceptible to outpatient visits for DM associated with NO2 and O3 exposure. In addition, we observed that an increased risk of DM outpatient visits was attributable to high concentration NO2 exposure, while high concentration O3 exposure was associated with a decreased risk of DM outpatient visits. This study provided a scientific basis for the etiology research and health protection of DM.

Helicobacter pylori infection may influence prevalence and disease course in myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD) similar to MS but not AQP4-IgG associated NMOSD.

Helicobacter pylori (Hp) persists after colonizing the gut in childhood, and potentially regulates host immune system through this process. Earlier studies have shown that Hp infection in childhood, may protect against MS in later life. Such an association was not seen with AQP4-IgG positive NMOSD, while the association with MOGAD is unclear. To evaluate frequency of Hp IgG among patients with MOGAD, MS, NMOSD and matched controls and its effect on disease course. To ascertain whether childhood socio economic factors were linked to prevalence of Hp infection. In all, 99 patients diagnosed to have MOGAD, 99 AQP4 IgG+ NMOSD, 254MS and 243 matched controls were included. Patient demographics, diagnosis, age at disease onset, duration and the last recorded expanded disability status scale (EDSS) were obtained from our records. Socioeconomic and educational status was queried using a previously validated questionnaire. Serum HpIgG was detected using ELISA kits (Vircell, Spain). Frequency of Hp IgG was significantly lower among MOGAD (28.3% vs 44%, p-0.007) and MS (21.2% vs 44%, p-0.0001) but not AQP4-IgG+ NMOSD patients (42.4% vs 44%, p-0.78) when compared to controls. Frequency of Hp IgG in MOGAD & MS patients combined (MOGAD-MS) was significantly lower than those with NMOSD (23.2% vs 42.4%, p- 0.0001). Seropositive patients with MOGAD- MS were older (p-0.001. OR -1.04, 95% CI- 1.01- 1.06) and had longer disease duration (p- 0.04, OR- 1.04, 95% CI- 1.002- 1.08) at time of testing. Educational status was lower among parents/caregivers of this study cohort (p- 0.001, OR -2.34, 95% CI- 1.48-3.69) who were Hp IgG+. In developing countries Hp infection may be a significant environmental factor related to autoimmune demyelinating CNS disease. Our preliminary data suggests that Hp may exert a differential influence -a largely protective role for MS-MOGAD but not NMOSD and may influence disease onset and course. This differential response maybe related to immuno-pathological similarities between MOGAD and MS in contrast to NMOSD. Our study further underscores the role of Hp as a surrogate marker for poor gut hygiene in childhood and its association with later onset of autoimmune diseases.

Autoimmune skin disorders and SARS-CoV-2 vaccination - a meta-analysis.

The coronavirus SARS-CoV-2, which is the cause of COVID-19 disease in infected patients, has led to an ongoing worldwide pandemic. Although SARS-CoV-2 vaccination had a dramatic positive effect on the course of COVID-19, there has been increasing evidence of adverse effects after SARS-CoV-2 vaccination. This meta-analysis highlights the association between SARS-CoV-2 vaccination and de novo induction or aggravation of inflammatory and autoimmune skin diseases. A systematic meta-analysis of the literature on new onset or worsening of inflammatory and autoimmune diseases after SARS-CoV-2 vaccination was performed according to the PRISMA guidelines. The search strategy included following terms: "COVID-19/SARS-CoV-2 vaccine bullous pemphigoid/pemphigus vulgaris/systemic lupus erythematosus/dermatomyositis/lichen planus/leukocytoclastic vasculitis." Moreover, we describe representative cases from our dermatology department. The database-search in MEDLINE identified 31 publications on bullous pemphigoid, 24 on pemphigus vulgaris, 65 on systemic lupus erythematosus, nine on dermatomyositis, 30 on lichen planus, and 37 on leukocytoclastic vasculitis until June 30th, 2022. Severity and response to treatment varied among the described cases. Our meta-analysis highlights a link between SARS-CoV-2 vaccination and new onset or worsening of inflammatory and autoimmune skin diseases. Moreover, the extent of disease exacerbation has been exemplified by cases from our dermatological department.

Origin, phenotype and autoimmune potential of T cells in human immune system mice receiving neonatal human thymus tissue.

Robust human immune system (HIS) mice are created using human fetal thymus tissue and hematopoietic stem cells (HSCs). A HIS mouse model using neonatal human thymus tissue and umbilical cord blood (CB) HSCs (NeoHu) was recently described. We improved the model by removing the native murine thymus, which can also generate human T cells, and demonstrated definitively the capacity of human T cells to develop in a grafted neonatal human thymus. Human T cells derived from the neonatal thymus tissue appeared in peripheral blood early post-transplantation and CB-derived T cells appeared later. Naïve T cells were demonstrated in peripheral blood but effector memory and T peripheral helper phenotypes predominated later, in association with development of autoimmunity in some animals. Treatment of thymus grafts with 2-deoxyglucose (2-DG) increased the proportion of stem cells derived from injected HSCs, delayed onset of autoimmune disease, reduced early T cell reconstitution, and reduced effector/memory T cell conversion. Younger neonatal human thymus tissue was associated with improved T cell reconstitution. While the NeoHu model bypasses the need for fetal tissue, it has yet to demonstrate equivalent reconstitution to fetal tissue, though 2-DG can improve results by removing native thymocytes prior to transplantation.