Chronic Immune Diseases Research Articles

Rise of a CD27- IgD- CD11c+ B cells population in kidney recipients achieving long-term graft stability under immunosuppression.

The use of immunosuppressive treatment is required to prevent rejection events, even a long time after kidney transplantation despite rare recipients achieving long-term graft stability without the need for immunosuppressive treatment, called operationally tolerant patients (TOLs). We comprehensively investigate the immune system of long-term IS recipients (LTTs) and TOLs to highlight their shared and unique immune features. Blood immune cell phenotyping was performed by spectral cytometry. Samples from 34 individuals were analyzed, including 6 LTTs, 8 TOLs, 10 stable patients at 1 year posttransplantation (STAs), and 10 healthy volunteers. B cells differed between LTTs and TOLs with a decreased total B-cell frequency and the acquisition of a memory phenotype in LTTs whereas a naive phenotype is maintained in TOLs. The frequencies of IgD-CD27- B cells and CD11c+ memory B cells are increased in LTTs, with an exhausted phenotype, evoked by a significant decrease in CD25 expression. These CD11c+ B cells display an exhausted phenotype similar to those found in several chronic immune diseases in which they have been shown to participate in their pathophysiology, suggesting active chronic inflammation in LTTs. Altogether, these data indicate that precautions should be taken to minimize IS use.

Ultra-low doses of microARNs restore a strong immune response in patients with Chronic Active Epstein-Barr Virus infection (CAEBV)

Chronic active Epstein-Barr Virus infection (CAEBV) is an abnormal response of the immune system to EBV infection, characterized by the absence of anti-EBNA (EBV Nuclear Antigens) IgG and associated with chronic fatigue and several immune related diseases. We present here an innovative therapeutic approach of CAEBV based on the use of ultra-low doses of non-coding RNAs (ncRNAs) involved in the host-virus interaction. We performed a retrospective study on 26 patients treated with our remedy. All the patients expect one developed positive EBNA IgG within eighteen months of starting treatment. Among the 25 cases that seroconverted, 75% report a significant improvement of their symptoms, especial of chronic fatigue. This study gives the proof of the efficiency of ultra-low doses of ncRNAs in restoring a strong immune response against EBV. More generally, this therapeutic approach can potentially be used in almost all pathologies.

Health-related quality of life in severe hypersensitivity reactions: focus on severe allergic asthma and hymenoptera venom anaphylaxis-a cross-sectional study.

Growing evidence reveals the important role of clinical psychological factors in chronic-immune diseases. The aim of this study was to investigate Health-Related Quality of Life (HR-QoL), depression, anxiety, and alexithymia in patients with severe hypersensitivity reactions such as Severe Allergic Asthma (SAA) and Hymenoptera Venom Anaphylaxis (HVA). The Short-Form Health Survey-36 (SF-36), the Beck Depression Inventory Questionnaire (BDI-II), the Hamilton Anxiety Rating Scale (HAM-A) and the Toronto Alexithymia Scale (TAS-20) were used to assess HR-QoL and clinical psychological features of patients with SAA and HVA. Overall, 78 patients were recruited. Patients with SAA (n = 35) reported lower scores for physical functioning [65 (58-75) vs. 90 (85-95); p = <0.001], role limitations due to physical health [25 (0-50) vs. 62 (50-75); p = 0.004], bodily pain [47.5 (41.1-61.3) vs. 55.5 (55-96); p = 0.001], general health [40 (30-60) vs. 70 (50-80); p = 0.0003] and social functioning [50 (37.5-62.5) vs. 62.5 (54.9-75); p = 0.007] while higher scores for depressive symptoms [14 (11-15.4) vs. (9.5 (6-15.4); p = 0.05)] compared to HVA patients (n = 43). All the dimensions of SF-36 were negatively correlated with anxiety (r from -0.26 to -0.66; p all < 0.01) and depressive symptoms (r from -0.44 to -0.73; p all < 0.001). Alexithymia was negatively correlated with vitality (r = -0.28; p = 0.02) and mental health (r = -027; p = 0.03). Additionally, patients with alexithymia (38% of participants) showed higher levels of depressive symptoms [9.5 (10-19) vs. 14 (6-13.9); p = 0.005] and anxiety levels [31 (27.9-35) vs. 24 (16-33.9); p = 0.02]; they also showed less vitality [40 (39.9-50) vs. 55 (50-60) p = 0.01], social functioning [50 (37.5-62.5) vs. 62.5 (50 vs. 75); p = 0.01] and mental health [48 (44-60) vs. 68 (56-76); p = 0.004]. Clinical psychological features due to severe hypersensitive reactions may contribute to the patient's perceived HR-QoL. Focused clinical psychological interventions should be promoted to improve the clinical management of such conditions.

One carbon metabolism and its implication in health and immune functions.

One carbon (1C) metabolism is critical for cellular viability and physiological homeostasis. Starting from its crucial involvement in purine biosynthesis to posttranslational modification of proteins, 1C metabolism contributessignificantly to the development and cellular differentiation through methionine and folate cycles that are pivotal for cellular function. Genetic polymorphisms of several genes of these pathways are implicated in disease pathogenesis and drug metabolism. Metabolic products of 1C metabolism have significant roles in epigenetic modifications through DNA and histone protein methylation. Homocysteine is a product that has clinical significance in the diagnosis and prognosis of several critical illnesses, including chronic immune diseases and cancers. Regulation of the function and differentiation of immune cells, including T-cells, B-cells, macrophages, and so forth, are directly influenced by 1C metabolism and thus have direct implications in several immune disease biology. Recent research on therapeutic approaches is targeting nuclear, cytoplasmic, and mitochondrial 1C metabolism to manage and treat metabolic (i.e., type 2 diabetes), neurodegenerative (i.e., Alzheimer's disease), or immune (i.e., rheumatoid arthritis) diseases. 1Cmetabolism is being explored for therapeutic intervention as a common determinant for a spectrum of immune and metabolic diseases. Identifying the association or correlation between essential metabolic products of this pathway and disease onset or prognosis would further facilitate the clinical monitoring of diseases.

Alexithymia and asthma: a systematic review.

Growing evidence from scientific research elucidates the important role of alexithymia in chronic immune diseases. This Review aims to explore the presence of alexithymia in patients affected by asthma and clarify its associations with other involved psychological and physical factors. In January 2023, according to PRISMA guidelines, a systematic search using PubMed and Scopus was conducted. Twenty-six studies were eligible based on inclusion criteria. Alexithymia was significantly present in asthma patients, with most studies reporting a higher prevalence (from 9 to 62.8%) than in control groups (approximately 10%). The coexistence of asthma and alexithymia was associated with a worse quality of life, psychiatric comorbidity, poor symptom control, and difficulty in recognizing exacerbations of the disease. These results suggest that alexithymia can negatively impact the management of asthma. For this reason, we recommend an accuracy assessment in clinical settings and the implementation of psychological interventions to promote the emotional and physical wellbeing of asthmatic patients.

Diffuse large B-cell lymphoma presenting as sternal mass in a patient with ankylosing spondylitis: a case report study.

The authors present a rare case of primary diffuse large B-cell lymphoma of the sternum in a 41-year-old Iranian woman with ankylosing spondylitis (AS). Physical examination revealed a 7×7.5cm firm swelling of the anterior midline chest wall above the breasts, and MRI showed a lesion within the sternal marrow with an associated soft-tissue mass in the anterior aspect of the sternum. Following core-needle biopsy under ultrasound guidance, a histopathological study demonstrated diffuse sheets of large noncleaved atypical cells with large multilobated prominent nuclei and fine chromatin compatible with diffuse large B-cell lymphoma. Primary and exclusive involvement of the sternum is an uncommon presentation of lymphoma. Radiological, histological, and clinical characteristics of primary bone lymphoma can resemble those of other medical disorders. Although infrequent, existing evidence shows that AS seems to be associated with a small but significant risk for malignancy. Even though inflammatory involvement of the anterior chest wall could be a common clinical finding in patients with AS, it is recommended that anterior chest wall pain or any mass almost always needs comprehensive assessment and imaging evaluation in such patients to avoid any delayed diagnosis, misdiagnosis, and ensuing morbidity or mortality.

The immune-supportive diet in allergy management: Anarrative review and proposal.

The role of nutrition is increasingly recognized in the management of chronic immune diseases. However, the role of an immune-supportive diet as adjuvant therapy in the management of allergic disease has not been similarly explored. This review assesses the existing evidence for a relationship between nutrition, immune function, and allergic disease from a clinical perspective. In addition, the authors propose an immune-supportive diet to enhance dietary interventions and complementing other therapeutic options for allergic disease from early life to adulthood. A narrative review of the literature was conducted, to determine the evidence of the relationship between nutrition and immune function, overall health, epithelial barrier function, and gut microbiome, particularly in relation to allergy. Studies on food supplements were excluded. The evidence was assessed and utilized to develop a sustainable immune-supportive diet to complement other therapies in allergic disease. The proposed diet consists of a highly diverse range of fresh, whole, and minimally processed plant-based and fermented foods supplemented with moderate amounts of nuts, omega-3-rich foods and animal-based products in proportional amounts of the EAT-Lancet diet, such as (fatty) fish, (fermented) milk products which may be full-fat and eggs, lean meat or poultry, which may be free-range or organic.

Adaptogens - use, history and future

Adaptogens are synthetic compounds or plant extracts that have the ability to increase the body's efficiency in the presence of stress stimuli. Extracts from ginseng, Eleutherococcus senticosus, Rhaponticum carthamoides, roseroot and chinensis are the best known plant adaptogens. The aim of this work is to assess the use of plant adaptogens in the past and present, and to outline the prospects for their future use. The use of natural adaptogens by humans has a rich history - they are used to treat many diseases, improve memory or reduce the effects of stress. Half a century ago, plant adaptogens were first used in competitive sports due to their effect on increasing the body's resistance to stress and improving physical endurance. Although many people now take plant adaptogens, human clinical trials are still very limited. Information obtained while writing this paper indicates that plant adaptogens may provide a number of benefits in the treatment of chronic fatigue, cognitive dysfunction and immune diseases.

Ready-To-Eat Rocket Salads as Potential Reservoir of Bacteria for the Human Microbiome.

Reportedly, Western-type diets may induce the loss of key microbial taxa within the gastrointestinal microbiota, promoting the onset of noncommunicable diseases. It was hypothesized that the consumption of raw vegetables could contribute to the maintenance of the intestinal microbial community structure. In this context, we explored bacteria associated with commercial rocket salads produced through different farming practices: traditional (conventional, organic, and integrated) and vertical farming. Viable counts of mesophilic bacteria and lactic acid bacteria (LAB) were performed on plate count agar (PCA) and de Man-Rogosa-Sharpe (MRS) agar at pH 5.7, whereas metataxonomics through 16S rRNA gene sequencing was used to profile total bacteria associated with rocket salads. We found that rocket salads from vertical farming had much fewer viable bacteria and had a bacterial community structure markedly different from that of rocket salads from traditional farming. Furthermore, although α- and β-diversity analyses did not differentiate rocket samples according to farming techniques, several bacterial taxa distinguished organic and integrated from conventional farming salads, suggesting that farming practices could affect the taxonomic composition of rocket bacterial communities. LAB were isolated from only traditional farming samples and belonged to different species, which were variably distributed among samples and could be partly associated with farming practices. Finally, the INFOGEST protocol for in vitro simulation of gastrointestinal digestion revealed that several taxonomically different rocket-associated bacteria (particularly LAB) could survive gastrointestinal transit. This study suggests that commercial ready-to-eat rocket salads harbor live bacteria that possess the ability to survive gastrointestinal transit, potentially contributing to the taxonomic structure of the human gut microbiota. IMPORTANCE Western-type diets are composed of foods with a reduced amount of naturally occurring microorganisms. It was hypothesized that a microbe-depleted diet can favor the alteration of the human intestinal microbial ecosystem, therefore contributing to the onset of chronic metabolic and immune diseases currently recognized as the most significant causes of death in the developed world. Here, we studied the microorganisms that are associated with commercial ready-to-eat rocket salads produced through different farming practices. We showed that rocket salad (a widely consumed vegetal food frequently eaten raw) may be a source of lactic acid bacteria and other microbes that can survive gastrointestinal transit, potentially increasing the biodiversity of the intestinal microbiota. This deduction may be valid for virtually all vegetal foods that are consumed raw.

Does the trained immune system play an important role in the extreme longevity that is seen in the Sardinian blue zone?

Villages in the island of Sardinia in the Mediterranean that display exceptional longevity are clustered within a defined mountainous region. Because of their unique location we hypothesize that these villages had a unique infectious disease exposure relevant to the observed successful longevity. These highland villages had a significant exposure to malaria in the first half of the 20th century after which malaria was eliminated due to vector control mechanisms. In addition, there is likely a high incidence of Helicobacter pylori infections among shepherds in Sardinia, the primary occupation of many living in the LBZ, as well as helminth infections among children. This suggests that individuals living in the LBZ had a unique infectious disease exposure. Specifically, we hypothesize that the continued high exposure of residents in the LBZ to these infectious agents prior to the 1950s lead to the generation of a uniquely trained (or imprinted) immune system. Once some of these diseases were eliminated in the latter half of the century, individuals within the LBZ were equipped with a trained immune system that was uniquely capable of not only responding effectively to common infections but also responding in a manner that maximized maintaining tissue health. In addition, there are lifestyle factors that also favor such a trained immune system. This hypothesis may help explain the slow progression of chronic immune mediated diseases as well as other chronic non-transmissible age-related diseases seen in the Sardinian LBZ and serve as a template for future studies that support or refute this hypothesis.

Differential genotypes of TNF-α and IL-10 for immunological diagnosis in discoid lupus erythematosus and oral lichen planus: A narrative review.

Discoid lupus erythematosus and oral lichen planus are chronic systemic immune system-mediated diseases with unclear etiology and pathogenesis. The oral mucosa is the common primary site of pathogenesis in both, whereby innate and adaptive immunity and inflammation play crucial roles. The clinical manifestations of discoid lupus erythematosus on the oral mucosa are very similar to those of oral lichen planus; therefore, its oral lesion is classified under oral lichenoid lesions. In practice, the differential diagnosis of discoid lupus erythematosus and oral lichen planus has always relied on the clinical manifestations, with histopathological examination as an auxiliary diagnostic tool. However, the close resemblance of the clinical manifestations and histopathology proves challenging for accurate differential diagnosis and further treatment. In most cases, dentists and pathologists fail to distinguish between the conditions during the early stages of the lesions. It should be noted that both are considered to be precancerous conditions, highlighting the significance of early diagnosis and treatment. In the context of unknown etiology and pathogenesis, we suggest a serological and genetic diagnostic method based on TNF-α and IL-10. These are the two most common cytokines produced by the innate and adaptive immune systems and they play a fundamental role in maintaining immune homeostasis and modulating inflammation. The prominent variability in their expression levels and gene polymorphism typing in different lesions compensates for the low specificity of current conventional diagnostic protocols. This new diagnostic scheme, starting from the immunity and inflammation of the oral mucosa, enables simultaneous comparison of discoid lupus erythematosus and oral lichen planus. With relevant supportive evidence, this information can enhance physicians’ understanding of the two diseases, contribute to precision medicine, and aid in prevention of precancerous conditions.

Pain and Fatigue Improvements in Patients Treated with Repository Corticotropin Injection Across Five Indications: A Narrative Review.

Repository corticotropin injection (RCI; Acthar® Gel) is approved by the US Food and Drug Administration (FDA) for use in 19 indications, including for the treatment of selected patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), symptomatic sarcoidosis, uveitis, and keratitis. Despite treatment with disease-modifying antirheumatic drugs, many patients with RA, SLE, and other chronic inflammatory rheumatic diseases continue to be affected by severe pain and fatigue, indicating a need for other therapies. To examine the clinical data regarding the impact of RCI treatment on pain and fatigue in selected populations, this review included English-language peer-reviewed publications of clinical trials of any size and cohort studies with more than 10 patients that included pain and/or fatigue based on patient-reported outcomes (PROs) and/or physician-assessed measures in adults following treatment with RCI for RA, SLE, symptomatic sarcoidosis, uveitis, or keratitis. Literature searches identified eight studies that met these criteria. Four studies (reported in five publications) were in patients with RA or SLE, two in patients with sarcoidosis, one in patients with uveitis, and one in patients with noninfectious keratitis. Across the different types of studies assessed (clinical trials, chart reviews, real-world evidence), the results were consistent with respect to the impact of RCI treatment on improving pain and fatigue. As summarized in this review, data from patient- and physician-reported outcome measures in eight studies demonstrate that, in addition to improving more traditional efficacy measures, RCI may also improve pain and fatigue in patients with RA, SLE, symptomatic sarcoidosis, uveitis, and noninfectious keratitis.

Dendrobium officinale leaf polysaccharides regulation of immune response and gut microbiota composition in cyclophosphamide-treated mice

In this study, the polysaccharides extracted from Dendrobium officinale leaf (DOLP) was used in immune deficiency mice to evaluate the bioactivity. Thymus and spleen indices were calculated while the alleviation of the colon and liver histopathological progression was evaluated by H&E staining. The data indicated that DOLP improved immunity status by restoring the gut barrier and atrophy of immune organs. Cytokines levels as marker of inflammation were determined using ELISA in serum and colon. Which proved that DOLP inhibited the expression of pro-inflammatory cytokines (TNF-α, TGF- β1, IL-6, IL-1β) and promoted the expression of anti-inflammatory cytokines (IL-10). Short chain fatty acids (SCFAs) levels and microbial composition in feces were determined using GS and high-throughput sequencing. DOLP improved gut microbiota by increasing the relative abundance of total bacteria and probiotics such as Bacteroides, Lactobacillus and Lachnospiraceae. Therefore, DOLP has potential effect for the treatment of chronic immune diseases.

ORTHOPAEDIC IMPLANT RELATED INFECTION

Implant is widely used to correct deformation, to stabilize fracture site, and promote bone healing in several orthopaedic surgeries. The use of implant is usually having a higher risk of developing infection. Although the use of antibiotic prophylaxis and antimicrobial impregnated biomaterial are used in cases of surgeries. But, the emerging superbugs which resistant to antibiotics, biofilms formation, and chronic immune suppressing diseases and lifestyles are challenging issues to make good osteosynthesis. Author use orthopaedic implant related infection to explain about the infection associated with the use of orthopaedic implants. This article attempts to discuss about infection associated with orthopaedic implant surgeries and treatment possible to treat the infection during implant placement.

Abstract 17062: Reversible Golimumab Induced Cardiomyopathy - First Reported Case Report

Case Presentation: An 80 year old female with medical history of hypertension, diabetes mellitus, chronic atrial fibrillation presented with four weeks of lower extremity edema and dyspnea. Notably, she had also been taking Golimumab for 6 months for Rheumatoid Arthritis (RA). Vital signs on presentations were: Temp:99 F, HR: 140bpm, BP: 105/64, oxygen saturation of 88% on room air. Physical exam revealed crackles at the mid lower lung fields bilaterally and 2+ lower extremity edema. EKG showed new ST inversions in lead 1, avF and V2. Troponin T was elevated to 0.11 ng/ml and proBNP was 21,246 pg/ml. Chest X Ray showed cardiomegaly with diffuse alveolar opacities. Transthoracic echocardiogram (TTE) revealed severely reduced left ventricular systolic function with LVEF of 25-29%, left ventricular regional wall hypokinesis and mildly reduced right ventricular systolic function. All findings were new compared to her last TTE 3 months prior, which showed preserved biventricular systolic function. Coronary angiography revealed no coronary artery disease. The patient was started on intravenous furosemide, and her home beta blocker and ARB were resumed. The patient’s Golimumab was discontinued given prior reports of TNF alpha inhibitor induced cardiomyopathy. Over the ensuing days, she was aggressively diuresed with improvement in oxygenation and ultimately discharged home. Three months after discontinuation of Golimumab, repeat TTE showed normalization of biventricular systolic function. Discussion: TNF alpha inhibitors have revolutionized the treatment of chronic immune mediated inflammatory diseases. Several TNF alpha inhibitors have been associated with cardiomyopathy, however there remains a paucity of evidence regarding cardiotoxicity with Golimumab. We now present, to our knowledge, the first reported case of reversible heart failure due to Golimumab in an 80 year old woman with RA. Golimumab, like other TNF alpha inhibitors, represents a historic advancement in the treatment of immune mediated inflammatory diseases. However, our case implicates this innovative drug in cardiotoxicity similar to other TNF alpha inhibitors. Further prospective studies are needed to establish a stronger correlation between Golimumab and cardiotoxicity.

ANTIOXIDANT CAPACITY IN PATIENTS WITH ORAL LICHEN PLANUS AND HEALTHY SUBJECTS-A COMPARATIVE STUDY

BACKGROUND AND AIM: Oral lichen planus is a common chronic inammatory disease of the oral mucosa with malignant potential. There are various antioxidant systems in body uid which can neutralize the reactive species. Impaired function of these systems leads to oxidative damage in the tissues and can result in the inappropriate activation of the immune system.Thus reduced antioxidant defense and increased oxidative stress may play an important role in etiology of many chronic immune mediated diseases such as: diabetes, psoriasis, vitiligo. Analyzing the antioxidant capacity in patients with OLP is of signicant value as it can provide essential clues in the etiology of the diseases and help in better management of the disease.This study aimed to assess and compare the antioxidant capacity of oral lichen planus patients and healthy subjects. MATERIALS AND METHODS:This study included 50 oral lichen planus patients and 50 healthy subjects . DPPH Assay is used to assess the antioxidant capacity in OLP patients and healthy subjects. The percentage scavenging of DPPH radical gave the antioxidant activity of the sample. RESULTS:Antioxidant level were reduced in the OLP group while comparing it with the control group. Mean antioxidant level in OLP group was 0.6 and that of the control group was 1.6. Comparison of mean antioxidant levels between the OLP group and control group showed signicant (p&lt;0.0001) difference. The difference between the reticular and erosive OLP group showed signicant difference with p value less than 0.0001. CONCLUSION:Antioxidant level signicantly decreased in OLP group compared to control group.Erosive OLP patients show low antioxidant level compared to reticular OLP patients.The ndings of present study support the hypothesis of the association between antioxidant capacity and OLP.

TYK2 inhibition and its potential in the treatment of chronic inflammatory immune diseases.

Immune-mediated chronic inflammatory diseases have emerged as a leading cause of morbidity and mortality in Western countries over the last decades. Although multiple putative factors have been suspected to be causally related to the diseases, their overarching etiology remains unknown. This review article summarizes the current state of scientific knowledge and understanding of the role of non-receptor tyrosine kinases, with a special focus on the Janus kinase TYK2 in autoimmune and immune mediated diseases as well as on the clinical properties of its inhibition. A panel of experts in the field discussed the scientific evidence and molecular rationale for TYK2 inhibition and its clinical application. Reviewing this meeting, we aim at providing an integrated overview of the clinical profile of TYK2 inhibition and its potential in targeted pharmacological therapy of chronic autoimmune and immune-mediated diseases, with a special focus on inflammatory diseases of the skin.

Time trends of chronic immune diseases by year of birth in Danish registries.

Chronic immune diseases are often reported to be on the rise and are speculated to share early life risk factors. Here, we investigated year of birth as a common denominator for time trends using the consistent data source of the Danish National Patient Registry with 35years nationwide coverage. Observational nationwide birth cohort registry study, where persons born in Denmark since 1953 were investigated for chronic immune diseases per person years at risk. Outcomes were defined by inpatient hospitalizations in pre-chosen age bins by year of birth in 5year bins. A population of 3.8 million persons born in Denmark since 1953 was investigated for a total sum of 68 million person years in the ages 5-34years. We found increasing trends by year of birth for juvenile arthritis age 10-14, adult asthma age 20-24, inflammatory bowel diseases age 20-24, and multiple sclerosis age 25-29, whereas type 1 diabetes age 15-19 was declining until birth year mid 1980s followed by a subsequent increase. Childhood asthma age 5-9 inpatient hospitalizations were relatively stable over time. Nationwide introduction of measles, mumps, rubella vaccine in 1987 did not alter the trends. Hospitalization for the chronic immune diseases adult asthma, juvenile arthritis, inflammatory bowel diseases and multiple sclerosis showed a general increasing trend by birth year in recent 35years while diabetes 1 and childhood asthma seemed stable in this period. These results were not affected by the introduction of vaccinations against the major childhood viral infections.

T cell protein tyrosine phosphatase protects intestinal barrier function by restricting epithelial tight junction remodeling.

Genome-wide association studies revealed that loss-of-function mutations in protein tyrosine phosphatase non-receptor type 2 (PTPN2) increase the risk of developing chronic immune diseases, such as inflammatory bowel disease (IBD) and celiac disease. These conditions are associated with increased intestinal permeability as an early etiological event. The aim of this study was to examine the consequences of deficient activity of the PTPN2 gene product, T cell protein tyrosine phosphatase (TCPTP), on intestinal barrier function and tight junction organization in vivo and in vitro. Here, we demonstrate that TCPTP protected against intestinal barrier dysfunction induced by the inflammatory cytokine IFN-γ by 2 mechanisms: it maintained localization of zonula occludens 1 and occludin at apical tight junctions and restricted both expression and insertion of the cation pore-forming transmembrane protein, claudin-2, at tight junctions through upregulation of the inhibitory cysteine protease, matriptase. We also confirmed that the loss-of-function PTPN2 rs1893217 SNP was associated with increased intestinal claudin-2 expression in patients with IBD. Moreover, elevated claudin-2 levels and paracellular electrolyte flux in TCPTP-deficient intestinal epithelial cells were normalized by recombinant matriptase. Our findings uncover distinct and critical roles for epithelial TCPTP in preserving intestinal barrier integrity, thereby proposing a mechanism by which PTPN2 mutations contribute to IBD.

Characterization of the blood microbiota in children with Celiac disease.

Celiac Disease (CD) is an autoimmune disorder triggered by gluten ingestion that can develop in genetically predisposed individuals. Alterations in the gut microbiota have been suggested to contribute to development of autoimmune conditions including CD. Recent work suggests the existence of a blood microbiota. Evidence that alterations in the blood microbiota potentially influence the development of chronic immune based diseases is increasing. However, there is no published literature regarding the blood microbiota in children, including those with CD. This study aimed to characterize the diversity and taxonomic composition of the blood microbiota of children with CD compared to controls. Whole blood samples were collected from children with active CD, CD in remission, and control subjects and 16S rRNA sequencing was utilized to analyze the blood microbiota. We found 16s rRNA present throughout all pediatric blood samples, providing evidence for the presence of a pediatric blood microbiota. We found significant differences in beta diversity and in abundance of certain taxa (Campylobacterales order, Odoribacteraceae and Helicobacteraceae families, Odoribacter genus and species, and Bacteroides acidifaciens species) between subjects with active CD and controls. These taxa have been previously reported to be associated with immune response and gut-inflammatory diseases. We did not find significant differences between subjects with active and remission CD or between remission CD and controls. Conclusions: We provide evidence for a pediatric blood microbiota and identified higher beta diversity and alterations in the composition of blood microbiota in subjects with active CD compared to controls.