Non-autoimmune Diseases Research Articles

Analysis of risk factors for autoimmune thyroid disease based on blood indicators and urinary iodine concentrations.

The aim of this study was to elucidate the relationships between thyroid hormones, lifestyle factors, biochemical markers, and autoimmune thyroid disease (AITD), thereby identifying the factors influencing the development of these diseases. The study encompassed 517 patients with AITD and 549 patients with non-autoimmune thyroid disease. Demographic and clinical data were collected, and various laboratory indicators, including urinary iodine and thyroid hormones, were measured and compared between the groups. Lasso regression was employed to select the independent variables, while logistic regression analysis determined the factors associated with the development of AITD. The prevalence of drinking alcohol history, median urinary iodine, and TSH concentrations proved significantly greater in the AITD group compared to the control group, while FT3 levels demonstrated lower values within the AITD group (p<0.05). Furthermore, there was a significant difference in the distribution of iodine nutrition status between the two groups (p<0.05). Both univariate and multivariate logistic regression analyses revealed significant associations among excessive iodine intake, drinking alcohol history, TSH, FT3, and the development of AITD. Excessive iodine intake and drinking alcohol history are implicated in an augmented risk of developing AITD. The prevention of AITD may necessitate the regular monitoring of TSH and FT3 concentrations.

Expression of integrin α4β1 and α4β7 on B cells correlates with autoimmune responses in Graves’ disease

BackgroundIntegrins are upregulated on endothelial cells and T-lymphocytes in autoimmune thyroid disease (AITD), potentially contributing to immune response localization. The role of integrins on B-cells in AITD remains unclear. MethodsPeripheral blood samples were collected from healthy controls (n = 56), patients with Graves’ disease (GD) (n = 37) and Hashimoto’s thyroiditis (HT) (n = 52). Ultrasound-guided fine-needle aspiration (FNA) of the thyroid was performed in patients with non-autoimmune thyroid disease (nAITD) (n = 19), GD (n = 11), and HT (n = 40). Integrins α4β7, α4β1, and αEβ7 in B cells were measured by flow cytometry. Serum zonulin levels were quantified via ELISA. Associations of integrins on B cells with thyroid hormones, thyroid autoantibodies, AITD duration, and zonulin were analyzed. ResultsHT patients exhibited lower α4β7 and higher α4β1 expression on B cells compared to healthy controls and GD patients. While α4β7 was predominant on circulating B cells, the dominant integrin expressed on intrathyroidal B cells varied with specific thyroid diseases. In GD patients, α4β7 and α4β1 expression on circulating B cells correlated positively and negatively with thyroid function and thyroid stimulating immunoglobulins (TSI) levels, respectively. Intrathyroidal α4β1+ B cells positively correlated with TSH levels in HT patients. Additionally, serum zonulin was elevated in HT patients, and intrathyroidal α4β7+ B cells and α4β1+ B cells correlated negatively and positively with zonulin levels, respectively. Integrin αEβ7 on B cells showed no significant association with AITD. ConclusionIntegrins expressed on B cells potentially play a role in the pathogenesis of AITD and might serve as immune biomarkers for the disease.

Effects of long-term magnesium L-threonate supplementation on neuroinflammation, demyelination and blood–brain barrier integrity in mice with neuromyelitis optica spectrum disorder

In clinical practice, we found cerebrospinal fluid magnesium concentration significantly lower in neuromyelitis optica spectrum disorder (NMOSD) patients compared to controls with non-autoimmune encephalitis neurological diseases. To investigate the effects and potential mechanisms of long-term magnesium supplementation on neuroinflammation, demyelination, and blood–brain barrier (BBB) integrity in NMOSD, we used two models: (1) NMOSD mouse model, which was induced by intraperitoneal injection of purified NMO-IgG to experimental autoimmune encephalomyelitis (EAE) mice, and (2) cultured human cerebral microvascular endothelial cells/D3 (hCMEC/D3). In the NMOSD mouse model, Magnesium L-threonate (MgT) pretreatment alleviated NMO-IgG–induced effects, including AQP4 loss, leukocyte infiltration, astrocyte and microglia activation, demyelination, decreased tight junction (TJ) protein expression, and neurological deficits. In vitro, MgT pretreatment ameliorated NMO-IgG induced damage to TJ protein expression in a (transient receptor potential melastatin 7) TRPM7-dependent manner. Magnesium supplementation shows potential protective effects against NMOSD, suggesting it may be a novel therapeutic approach for this condition. The beneficial effects appear to be mediated through preservation of blood–brain barrier integrity and reduction of neuroinflammation and demyelination.

Assessment of thiol-disulfide and glutathione homeostasis after levothyroxine replacement in individuals with autoimmune or nonautoimmune hypothyroidism.

Thyroid hormones are known to affect the biosynthesis and degradation of antioxidant compounds, suggesting a possible link between hypothyroidism and oxidative stress. However, there is no clear consensus in the literature regarding this association. The aim of this study was to evaluate oxidative stress markers (extracellular thiol-disulfide homeostasis and intracellular glutathione homeostasis) in patients with hypothyroidism due to autoimmune (Hashimoto's thyroiditis) or nonautoimmune thyroid disease rendered euthyroid after levothyroxine replacement. The study included 116 patients admitted to the Taksim Training and Research Hospital (Istanbul, Türkiye). Of these, 50 had hypothyroidism due to Hashimoto's thyroiditis (HT group), 30 had nonautoimmune hypothyroidism (NAIH group), and 36 were healthy controls (control group). All participants were women. Extracellular thiol-disulfide homeostasis and intracellular glutathione homeostasis tests were assessed as oxidative stress markers. Thiol-disulfide homeostasis in both HT and NAIH groups was shifted toward the oxidative spectrum. Compared with the control group, the HT and NAIH groups had lower levels of native (p < 0.001 and p = 0.001, respectively) and total (p = 0.002 and p = 0.012, respectively) thiol, as well as a lower native thiol/total thiol ratio (p < 0.001 for both). The HT group also had higher disulfide levels than the control group (p = 0.027). Reduced glutathione (GSH) and oxidized glutathione (GSSG) values were comparable across all three groups, but the HT and NAIH groups had higher GSSG/GSH (p < 0.001 for both) and GSSG/(GSH+GSSG) ratios (p = 0.003 and p = 0.005, respectively), along with lower GSH/(GSH+GSSG) ratio (p = 0.001 and p = 0.002, respectively) than the control group. Levothyroxine replacement was ineffective in ameliorating oxidative stress in patients with hypothyroidism due to Hashimoto's thyroiditis or nonautoimmune causes, as extracellular thiol-disulfide homeostasis was notably altered in these patients compared with healthy controls. The findings of this study suggest that oxidative stress remains a prevailing issue in patients with autoimmune or nonautoimmune hypothyroidism even after euthyroidism is restored.

Multimodal Approach in Dry Eye Disease Combining In Vivo Confocal Microscopy and HLA-DR Expression.

The purpose of this study was to determine the association between corneal images provided by in vivo confocal microscopy (IVCM) with clinical parameters and conjunctival expression of HLA-DR antigen in patients with dry eye disease (DED). Two hundred fourteen eyes of 214 patients with DED were analyzed, consisting of 2 groups of patients - 63 with autoimmune dry eye disease (AIDED) and 151 with non-autoimmune dry eye disease (NAIDED). Patients underwent a full clinical examination, including symptom screening, using the Ocular Surface Disease Index (OSDI) questionnaire, and objective analysis of DED signs by Schirmer's testing, tear break-up time (TBUT), Oxford's test, and IVCM corneal imaging. The IVCM scoring criteria were based on corneal sub-basal nerve density (ND), nerve morphology (NM), and inflammatory cell (IC) density. Quantification of conjunctival HLA-DR antigen was performed by flow cytometry. The total IVCM score (T-IVCM) as well as the IVCM-IC subscore (sc) were positively correlated with HLA-DR levels with r = 0.3, P < 0.001 and r = 0.3, P < 0.01, respectively in the total population of patients with DED. The IVCM-NDsc was negatively correlated with TBUT in patients with AIDED (r = -0.2, P < 0.05) and with the Schirmer's test in patients with NAIDED (r = -0.24, P < 0.05). However, the IVCM-NMsc was positively correlated with the Oxford score only in patients with AIDED (r = 0.3, P < 0.05). The proposed IVCM scoring system showed significant correlations with clinical parameters along with conjunctival HLA-DR quantification in patients with DED. The IVCM grading score represents an interesting point of commonality among clinical parameters, imaging, and molecular investigation of the ocular surface.

Gut microbiota in autoimmune and non-autoimmune liver diseases in children

Relevance. The influence of the gut microbiota on the development of various diseases is of great interest to researchers. The conducted studies showed that in patients with chronic liver diseases, the dominant taxa of the gut microbiota were Bifidobacterium longum, Bifidobacterium adolescentis, Blautia massiliensis, and in healthy children - Neisseria flavescens. There is no comparative analysis of data on the taxonomic diversity of the intestinal microbiota in autoimmune and non-autoimmune liver diseases in children. Purpose of the study. To investigate differences in the taxonomic diversity of fecal microbiota in patients with autoimmune and non-autoimmune liver diseases, as well as to evaluate potential biomarkers of 16S rRNA gene amplicons in these diseases by comparing the taxonomic composition. Scope and methods of research. A metagenomic analysis of the intestinal microbiota of 24 children with chronic liver diseases (mean age 10.3±4.7 years) was carried out with the identification of the V3-V4 region of the 16S rRNA gene. The group included 18 children with autoimmune liver diseases and 6 children with non-autoimmune liver diseases. Research results. The conducted study revealed 684 types of microorganisms in the studied samples of patients’ faeces. The analysis of the conducted studies showed that no dominant taxa were found in the faecal samples of children with autoimmune liver diseases, while Veillonella dispar, Veillonella parvula, Cloacibacillus porcorum, Prevotella histicola and Bacteroides eggerthii were the dominant taxa in patients with non-autoimmune liver diseases. Conclusion. Studies have shown differences in the composition of the gut microbiota in children with autoimmune and non-autoimmune liver diseases.

Comparative assessment of intestinal microbiota in autoimmune and non-autoimmune liver diseases in children

The influence of the gut microbiota on the development of various diseases is of great interest to researchers. The conducted studies showed that in patients with chronic liver diseases, the dominant taxa of the gut microbiota were Bifidobacterium longum, Bifidobacterium adolescentis, Blautia massiliensis, and in healthy children — Neisseria flavescens. There is no comparative analysis of data on the taxonomic diversity of the intestinal microbiota in autoimmune and non-autoimmune liver diseases in children. Purpose. To investigate differences in the taxonomic diversity of fecal microbiota in patients with autoimmune and non-autoimmune liver diseases, as well as to evaluate potential biomarkers of 16S rRNA gene amplicons in these diseases by comparing the taxonomic composition. Material and methods. A metagenomic analysis of the intestinal microbiota of 24 children with chronic liver diseases (mean age 10,3 ± 4,7 years) was carried out with the isolation of the 16S rRNA gene region. The group included 18 children with autoimmune liver diseases and 6 children with non-autoimmune liver diseases. Results. The conducted study revealed 684 types of microorganisms in the studied samples of patients’ feces. The analysis of the conducted studies showed that no dominant taxa were found in the fecal samples of children with autoimmune liver diseases, while Veillonella dispar, Veillonella parvula, Cloacibacillus porcorum, Prevotella histicola and Bacteroides eggerthii were the dominant taxa in patients with non-autoimmune liver diseases. Conclusion. Studies have shown differences in the composition of the gut microbiota in children with autoimmune and non-autoimmune liver diseases.

Characteristics of long COVID in patients with autoimmune rheumatic diseases: a systematic review and meta-analysis.

Numerous cases of long coronavirus disease (long COVID) have been reported in patients with autoimmune rheumatic diseases (ARDs). Despite the reviews on clinical manifestations of long COVID in the general population, systematic reviews on ARD patients are scarce. Herein, we conducted a systematic review and meta-analysis on the prevalence and characteristics of long COVID in ARD patients. We searched the literature in PubMed and Embase as of 27 December 2022. Cohort, cross-sectional and case-control studies relevant to long COVID in ARD patients were collected. Stratification based on the severity of COVID infection and subtypes of rheumatic diseases [systemic autoimmune rheumatic disease (SARD) vs non-autoimmune rheumatic disease (NARD)] was also undertaken. A random-effects model was used in the meta-analysis. A total of 15 relevant studies were identified from the literature. The prevalence of long COVID was 56% (95% CI 34, 76) in 2995 patients. Hospitalized COVID patients had a higher proportion of long COVID than non-hospitalized patients. The prevalence of long COVID was similar between SARD and NARD patients. In terms of symptoms, fatigue, arthralgia and pain were commonly reported in long COVID patients with ARDs. The characteristics of long COVID in ARD patients are generally similar to those in the general population despite a higher prevalence and a higher proportion of arthralgia and pain.

Measurement of Neutrophil Extracellular Traps as a Biomarker for the Differential Diagnosis Between Antineutrophil Cytoplasmic Antibody-Positive Individuals With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Nonautoimmune Diseases.

Neutrophil extracellular traps (NETs) have a correlation with disease activity in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, it is not known whether there is an association between NETs and the presence of ANCA in other diseases. This study aimed to assess the occurrence of NETs in individuals with ANCA and whether serum NET quantitation is capable of distinguishing them with regard to the diagnosis. This was a cross-sectional, observational study. From the positive ANCA by indirect immunofluorescence, 94 individuals were divided into groups: AAV, infectious diseases, and neoplastic diseases. Healthy controls served for comparisons. Neutrophil extracellular traps were evaluated through the investigation of NET remnants, by detecting cell-free DNA bound to proteins such as histone, myeloperoxidase, and neutrophil elastase (NE). In patients with perinuclear ANCA (p-ANCA) the detection of NETs by NE was able to distinguish AAV from infection/neoplasia and healthy controls. Receiver operating characteristic curves for serum NETs by NE in patients with p-ANCA were drawn in 2 situations: AAV versus infection/neoplasia, showing a sensitivity of 0.65 and specificity of 0.84, with an area under the curve of 65%; and AAV versus controls, showing a sensitivity of 0.84 and a specificity of 0.88, with an area under the curve of 96%. For p-ANCA-positive individuals, we found higher serum NETs detected by NE-DNA in those with chronic infectious and neoplastic diseases than in AAV individuals and healthy controls. This allows us to infer that the evaluation of serum NETs may be of value as a biomarker for differential diagnosis.

Canine diabetes mellitus demonstrates multiple markers of chronic inflammation including Th40 cell increases and elevated systemic-immune inflammation index, consistent with autoimmune dysregulation.

Canine diabetes mellitus (CDM) is a relatively common endocrine disease in dogs. Many CDM clinical features resemble human type 1 diabetes mellitus (T1DM), but lack of autoimmune biomarkers makes calling the disease autoimmune controversial. Autoimmune biomarkers linking CDM and T1DM would create an alternative model for drug development impacting both human and canine disease. We examined peripheral blood of diagnosed CDM dog patients comparing it to healthy control (HC) dogs. Dogs were recruited to a study at the Colorado State University Veterinary Teaching Hospital and blood samples collected for blood chemistry panels, complete blood counts (CBC), and immunologic analysis. Markers of disease progression such as glycated albumin (fructosamine, the canine equivalent of human HbA1c) and c-peptide were addressed. Significant differences in adaptive immune lymphocytes, innate immune macrophages/monocytes and neutrophils and differences in platelets were detected between CDM and HC based on CBC. Significant differences in serum glucose, cholesterol and the liver function enzyme alkaline phosphatase were also detected. A systemic immune inflammation index (SII) and chronic inflammation index (CII) as measures of dynamic changes in adaptive and innate cells between inflammatory and non-inflammatory conditions were created with highly significant differences between CDM and HC. Th40 cells (CD4+CD40+ T cells) that are demonstrably pathogenic in mouse T1DM and able to differentiate diabetic from non-diabetic subjects in human T1DM were significantly expanded in peripheral blood mononuclear cells. Based on each clinical finding, CDM can be categorized as an autoimmune condition. The association of significantly elevated Th40 cells in CDM when compared to HC or to osteoarthritis, a chronic but non-autoimmune disease, suggests peripheral blood Th40 cell numbers as a biomarker that reflects CDM chronic inflammation. The differences in SII and CII further underscore those findings.

The Health-Related Quality of Life in Patients with Dry Eye Syndrome Classified by Severity and Causes Including the Autoimmune and Non-autoimmune Diseases: A Cross-sectional Study in Thailand

Background: The common causes of Dry eye syndrome (DES) were autoimmune or non-autoimmune disorders. DES is common but lack of data in quality of life (QoL) of DES patients in Thailand. The primary outcome of this study was to determine QoL and health utility in patients of DES by EuroQol 5-domain (EQ-5D) of the 5-level version (5L) instrument. The secondary outcome was comparison of the utility in the patients of DES classified by severity and causes including the autoimmune and non-autoimmune diseases. Methods: The study was a cross-sectional study at a hospital in the northern part of Thailand. The inclusions DES patients were followed by Tear Film and Ocular surface Society the Dry Eye WorkShop II definition. The EQ-5D-5L (Thai version) descriptive system and the EQ visual analogue scale (VAS) was instrument for QoL evaluation. Results: Total patients of DES were fifty-six. The most patients were female. The mean age was 57.7(± 13.9) years. Most patients (94.6%) were female. The mean age was 59.7 (± 13.9) years old. The median time from diagnosis of DES was 4.7 years (IQR = 2.2 to 6.8 years). The common cause of DES associated was autoimmune disease. Primary Sjogren syndrome and idiopathic causes were the most common causes in autoimmune diseases and non- autoimmune diseases, respectively. In autoimmune disease, Primary Sjogren syndrome, was 41.18%. The most common causes of non-autoimmune diseases were idiopathic. The mean of EQ-5D-utility and EQ-VAS of DES were 0.76 (± 0.18) and 72.86 (± 15.19), respectively. The mean of EQ-5D-utility and EQ-VAS in these patients who were classified by severity including mild, moderate and severe were 0.84 (± 0.16) and 67.31(± 15.76), 0.78 (± 0.14) and 74.47 (± 15.71), 0.71 (± 0.22) and 74.58 (± 14.36), respectively. The mean of EQ-5D-utility and EQ-VAS in these patients who were classified by autoimmune or non-autoimmune disorders were 0.75 (± 0.21) and 75.78 (± 14.21), 0.78 (± 0.15) and 68.96 (± 15.88), respectively. There is no statistic significant in the EQ-5D-utility and EQ-VAS among severity and the causes including autoimmune or non-autoimmune disorders of these patients. Conclusions: This study demonstrated the importance of assessing QoL in DES. Primary Sjogren syndrome and idiopathic causes were the most common causes in autoimmune diseases and non-autoimmune diseases, respectively. The EQ-5D-utility was accorded with the severity of DES. However, no statistic significant was showed in the mean of EQ-5D-utility and EQ-VAS between the severity and between the causes including the autoimmune and non-autoimmune diseases of these patients.

The Role and Mechanism of Autoantibodies in Dysimmunity Related Neurological Diseases

Autoantibodies are antibodies produced by B cells capable of attacking their own tissues or organs after loss of immune tolerance. A large body of literature shows that autoantibodies play an important role in neurological diseases associated with immune abnormalities. Nowadays, neurological disorders are an important cause of disability and death in populations around the world, so it is important to study the role and mechanisms of autoantibodies in neurological disorders associated with immune abnormalities. The blood-brain barrier is biologically important for maintaining the normal physiological state of the central nervous system, and we have previously found that monoclonal autoantibodies of SLE origin can inhibit the expression of tight junction proteins in the blood-brain barrier. Our findings provide clues for the study of the role of autoantibodies in neurological disorders and greatly attract us to conduct a more in-depth and systematic review and synthesis. In this paper, we summarize the functions of autoantibodies in autoimmune and non-autoimmune diseases and focus on the roles and mechanisms of autoantibodies in immune-associated neurological disorders by taking central and peripheral neurological diseases as the entry points, which can provide new molecular targets and new theoretical basis for the specific diagnosis and targeted therapy of neurological diseases.

Intolerance of gluten-containing cereals

Intolerance of gluten containing cereals (wheat, rye and barley) is an etiopathogenetically heterogeneous and relatively common problem of modern man. It occurs as an adverse immune-mediated condition in genetically pre-disposed individuals. According to the pathogenetic mechanism of intolerance to the components of these cereals, it is classified into celiac disease as an autoimmune disease, wheat allergy as an allergic disease, and non-celiac gluten sensitivity as a non-autoimmune and non-allergic disease. Each of these disorders is characterized by specific intestinal and/or extraintestinal manifestations, which resolve on a gluten-free diet. This review article presents the basic characteristics of these disorders in accordance with modern knowledge.

Clinical Characteristics and Prognosis of Acute Pulmonary Embolism with Hemoptysis in Autoimmune Disease Patients.

Background: Hemoptysis is prevalent in acute pulmonary embolism (PE) and significantly influences clinical decision-making. Despite the increasing reports of PE in patients with autoimmune diseases, limited studies have investigated the association between acute PE with hemoptysis and autoimmune disease. Methods: The retrospective study aimed to investigate patients with autoimmune disease who presented with acute PE and hemoptysis at Peking Union Medical College Hospital (PUMCH) between January 2012 and October 2020. A comparative analysis was conducted between patients with and without hemoptysis, as well as between those with autoimmune diseases and those without. Clinical characteristics, PE severity stratification, the amount of hemoptysis, initial anticoagulation management, and prognosis were analyzed descriptively. Results: The study analyzed 896 patients diagnosed with acute PE, of whom 105 (11.7%) presented with hemoptysis. Hemoptysis in PE patients was frequently associated with autoimmune diseases (39%, 41/105), a younger patient population (42.0 vs. 52.7 years old, P =0.002), and a higher prevalence of low-risk PE (53.7 vs. 28.1, P=0.008) compared with non-autoimmune disease patients. Multivariate logistic analysis showed PE patients with primary or metastatic lung cancer, chest pain, age < 48 years old, chronic heart failure, autoimmune disease, pulmonary infection and male were more likely to develop hemoptysis. Patients were grouped based on maximum daily sputum blood volume and PE risk stratification. Most patients (73.2%) received therapeutic-dose anticoagulation. Poor prognosis is observed in patients with moderate to massive hemoptysis and intermediate-high-risk or high-risk PE. Conclusions: Hemoptysis is a relatively common manifestation in patients with PE, and its presence during the diagnostic workup of acute PE necessitates careful analysis of underlying comorbidities. In cases where hemoptysis occurs in individuals with autoimmune diseases in the context of PE, proactive management strategies targeting the primary disease are crucial. Therapeutic decisions should consider both PE severity stratification and the volume of hemoptysis.

Immunomodulators as objects of the pharmaceutical market. Message III. The product conjuncture of immunosuppressants and their place in the state guarantees program of medical care of the population

Immunosuppressants (ІS) are used to prevent a number of autoimmune diseases, non-autoimmune inflammatory diseases and rejection of transplanted organs. Global ІS market is characterized by high growth rates.&#x0D; The aim of the work: analyze the immunosuppressants product nomenclature on the pharmaceutical market of Ukraine, as well as their characteristics from the point of view of state guarantees of medical care of the population.&#x0D; The research materials: the sources of special and scientific and methodical literature; The State Register of Drugs of Ukraine (as of February 1, 2023), the Register of Drugs that are subjects to reimbursement by the state guarantees program of medical care of the population, as of February 14, 2023. The methods of information search, analysis, generalization, and marketing research have been used.&#x0D; It has been established that 27 INN of immunosuppressants in the form of 134 trade names had been registered in Ukraine. Almost half of the studied drugs consisted of lenalidomide (23.13%), tacrolimus (15.67%) and mycophenolic acid (9.70%). Immunosuppressants are presented in the shape of 7 dosage forms, mostly in capsules (55.22%).&#x0D; It has been found that immunosuppressants are characterized by absolute import dependence, 127 foreign manufacturers from 27 countries have registered 133 trade names (99.25%), and the Ukrainian manufacturer (JSC "Farmak") - only one position (0.75%) and even that is from products in bulk. Germany is characterized as the country that has the highest production activity of immunosuppressants (22.83% of the enterprises had an indicator of production activity of 20.81%), and among the producers there are two pharmaceutical enterprises: Novartis Pharma Stein AG, Switzerland and Sinton Hispania S.L, Spain (production activity indicator 3.76% both).&#x0D; The Register of drugs subjects to reimbursement under the state guarantees program of medical care of the population has included 5 INN of immunosuppressants in the form of 21 trade names for people in the post-transplantation period. Four-fifths (80.95%) of them belong to expensive drugs, as evidenced by their retail price per package of UAH 1,000 or more. However, patients can receive 15 trade names free of charge, for the other 6 trade names patient’s payment ranges from 8.09 to 33.95% of retail value.&#x0D; The obtained results can serve as a prototype for the formation of the product nomenclature of drug manufacturers, wholesale pharmaceutical enterprises and pharmacies.

The Presence, Location, and Degree of Late Gadolinium Enhancement in Relation to Myocardial Dysfunction and Poor Prognosis in Patients with Systemic Lupus Erythematosus.

Patients with systemic lupus erythematosus (SLE) typically develop myocardial fibrosis. No studies have investigated the clinical significance of the presence, location, and degree of fibrosis in SLE patients. Seventy-four SLE patients were included. Thirty-seven non-autoimmune disease patients and thirty-seven healthy individuals were included as controls. Myocardial fibrosis was evaluated at cardiac magnetic resonance via a qualitative and quantitative assessment of late gadolinium enhancement (LGE). Myocardial function was measured via speckle-tracking echocardiography. All patients were followed up for the occurrence of major adverse cardiac events (MACE). The presence, locations, and degrees of LGE disturbed regional and global myocardial function. The presence of LGE, left ventricular free-wall LGE (LVFW LGE), and severe LGE were all independent predictors of MACE in SLE patients [LGE presence HR: 3.746 (1.434-9.79), p = 0.007; LVFW LGE HR: 2.395 (1.023-5.606), p = 0.044; severe LGE HR: 3.739 (1.241-11.266), p = 0.019]. LGE combined with SLE-related organ damage identified patients at high risk of MACE (p < 0.001). In conclusion, the presence, degree, and location of LGE were associated with myocardial dysfunction. The presence, location, and degree of LGE had the potential to independently predict poor prognosis and improve risk stratification in SLE patients.

Autoantibodies to beta tubulin in autoimmune liver diseases-Relation to pANCA and clinical relevance.

There was evidence that perinuclear antineutrophil cytoplasmic antibodies (pANCA) in autoimmune liver diseases react with human beta-tubulin-5 (TBB5). Here, we reevaluate the specificity and clinical relevance of anti-TBB5 antibodies. Patients with untreated autoimmune hepatitis (AIH; n = 53), AIH under immunosuppressive therapy (AIH-IS; n = 125), primary sclerosing cholangitis (PSC; n = 40), primary biliary cholangitis (PBC; n = 250), nonautoimmune liver diseases (n = 158), inflammatory bowel diseases (IBD; n = 30), and healthy individuals (n = 62) were tested by enzyme-linked immunosorbent assay for IgG- and IgA-antibodies against recombinant human TBB5. pANCA were detected by immunofluorescence test. Sera were absorbed with TBB5 coupled to cyanogen bromide-activated sepharose. Prevalence and reactivity of IgG anti-TBB5 were significantly higher in patients with untreated AIH (68%; arbitrary units [AU] median: 369) than in PSC (28%; AU median: 84, P < 0.001), other liver diseases (14%; AU median: 185, P < 0.0001), IBD (3%; AU median: 111, P < 0.0001), and healthy controls (3%; AU median: 135; P < 0.0001). Anti-TBB5 did not correlate with pANCA, and immunoprecipitation with TBB5 did not abolish pANCA reactivity. In untreated AIH, anti-TBB5-reactivity was significantly higher than in AIH-IS. Transaminases decreased under IS preferentially in anti-TBB5-negative patients. There was no correlation between anti-TBB5-reactivity and histological stages. IgA-anti-TBB5 was mainly found in alcohol-associated liver disease (ALD; 39%). Our data do not support TBB5 as an autoantigenic target of pANCA. However, IgG-anti-TBB5 showed high specificity for (untreated) AIH. While they did not correlate with histological and laboratory parameters, their presence may indicate a poor response to IS.

Features of the gut microbiota in children with chronic liver diseases

The value of the liver–gut axis is increasingly recognized as a major modulator of autoimmunity. There is no comparative analysis of data on the taxonomic diversity of the intestinal microbiota in chronic liver diseases in children. Purpose. To investigate the taxonomic diversity of the intestinal microbiota in children with chronic liver diseases compared with healthy patients, to identify differences in bacterial diversity in autoimmune and non-autoimmune liver diseases, as well as the impact of immunosuppressive therapy on the intestinal microbiota. Material and methods. A metagenomic analysis of the gut microbiota of 24 children with chronic liver diseases (mean age 10,3 ± 4,7 years) was carried out with the identification of the V3–V4 region of the 16S rRNA gene. The group included 18 children with autoimmune liver diseases and 6 children with non-autoimmune liver diseases. The control group consisted of fecal samples of 34 apparently healthy children. Results. When comparing fecal samples of children with autoimmune liver diseases with samples of healthy children, the taxa of Bacteroides dorei, Collinsella aerofaciens, Ruminococcus caffidurs prevailed, and for children of the control group — Neisseria flavescens. When comparing samples of patients with non-autoimmune liver diseases and the control group, it was found that the taxa Bacteroides fragilis, Klebsiella pneumoniae, Bifidobacterium longum prevailed in healthy children. When comparing fecal samples from children with autoimmune and non-autoimmune liver diseases, it was found that Veillonella dispar, Cloacibacillus porcorum, Veillonella parvula, Prevotella histicola and Bacteroides eggerthii taxa dominate in patients with non-autoimmune diseases. No dominant taxa of the gut microbiota were found in children with autoimmune liver diseases. It has been established that the taxa Veillonella dispar, Faecalibacterium prausnitzii, Roseburia inulinivorans, Bacteroides xylanisolvens and Alistipes obesi prevail in patients receiving immunosuppressive therapy, and the taxa Phascolarctobacterium succinatutens, Bacteroides ovatus, Solobacterium mooreis and Holdemanella massilien prevail in patients not receiving immunosuppressive therapy. Conclusion. A recent study of the gut microbiota in children with chronic liver disease shows differences in the imbalance of the gut microbiota compared to the results obtained in adults. The gut microbiota model is capable of distinguishing autoimmune liver diseases from non-autoimmune diseases. Immunosuppressive therapy is accompanied by the dominance of taxa that reduce the production of short-chain fatty acids.

Clinical diagnoses associated with a positive antinuclear antibody test in patients with and without autoimmune disease

BackgroundAntinuclear antibodies (ANA) are antibodies present in several autoimmune disorders. However, a large proportion of the general population (20%) also have a positive test; very few of these individuals will develop an autoimmune disease, and the clinical impact of a positive ANA in them is not known. Thus, we test the hypothesis that ANA + test reflects a state of immune dysregulation that alters risk for some clinical disorders in individuals without an autoimmune disease.MethodsWe performed high throughput association analyses in a case–control study using real world data from the de-identified electronic health record (EHR) system from Vanderbilt University Medical Center.The study population included individuals with an ANA titer ≥ 1:80 at any time (ANA +) and those with negative results (ANA-). The cohort was stratified into sub-cohorts of individuals with and without an autoimmune disease. A phenome-wide association study (PheWAS) adjusted by sex, year of birth, race, and length of follow-up was performed in the study cohort and in the sub-cohorts. As secondary analyses, only clinical diagnoses after ANA testing were included in the analyses.ResultsThe cohort included 70,043 individuals: 49,546 without and 20,497 with an autoimmune disease, 26,579 were ANA + and 43,464 ANA-. In the study cohort and the sub-cohort with autoimmune disease, ANA + was associated (P ≤ 5 × 10–5) with 88 and 136 clinical diagnoses respectively, including lupus (OR ≥ 5.4, P ≤ 7.8 × 10–202) and other autoimmune diseases and complications. In the sub-cohort without autoimmune diseases, ANA + was associated with increased risk of Raynaud’s syndrome (OR ≥ 2.1) and alveolar/perialveolar-related pneumopathies (OR ≥ 1.4) and decreased risk of hepatitis C, tobacco use disorders, mood disorders, convulsions, fever of unknown origin, and substance abuse disorders (OR ≤ 0.8). Analyses including only diagnoses after ANA testing yielded similar results.ConclusionA positive ANA test, in addition to known associations with autoimmune diseases, Raynaud’s phenomenon, and idiopathic fibrosing alveolitis related disorders, is associated with decreased prevalence of several non-autoimmune diseases.

Effect of ursodeoxycholic acid on the intestinal microbiota in children with chronic liver disease

Ursodeoxycholic acid is a secondary bile acid (BA), present in humans at low concentrations, with well-known therapeutic properties, and was originally used to treat cholestatic liver disease. However, there are very few studies on the effect of ursodeoxycholic acid on the composition of the gut microbiota, especially in children with chronic liver diseases.Purpose. To determine differences in the taxonomic diversity of the fecal microbiota in children with chronic liver disease who receive or do not receive ursodeoxycholic acid.Material and methods. A metagenomic analysis of the intestinal microbiota of 24 children with chronic liver diseases (mean age 10.3 ± 4.7 years) was carried out with the identification of the V3–V4 region of the 16S rRNA gene. The group included 18 children with autoimmune liver diseases and 6 children with non-autoimmune liver diseases. 17 children received ursodeoxycholic acid. The comparison group consisted of 7 children who did not receive ursodeoxycholic acid.Results. This study found that fecal samples from patients treated with ursodeoxycholic acid do not differ in the taxonomic diversity of the gut microbiota from samples from patients not treated with ursodeoxycholic acid. A more detailed study to determine the existing taxonomic diversity in samples of patients treated with ursodeoxycholic acid and not treated with ursodeoxycholic acid, using the sPLS-DA method, showed that taxa such as Streptococcus anginosus, Coprococcus eutactus, Desulfovibrio desulfuricans, Angelakisella massiliensis and Gemella haemolysans dominated in patients not treated with ursodeoxycholic acid. And for patients receiving drugs with ursodeoxycholic acid, the dominance of the taxon Anaerostipes hadrus is typical. An analysis of differences in the percentage of intestinal microbiota bacterial species showed that patients receiving ursodeoxycholic acid had a higher count of Anaerostipes hadrus, while in patients not receiving ursodeoxycholic acid preparations, the count of Bacteroides dorei, Akkermansia muciniphila was significantly increased, and the counts of other bacteria were also increased.Conclusion. Studies have shown that ursodeoxycholic acid has a positive effect on the intestinal microbiota in children with chronic liver disease by increasing the number of microorganisms that produce short-chain fatty acids.