Autoimmune Process Research Articles

A higher incidence of cardiovascular complications in hyperthyroid patients with Graves’ disease in comparison to hyperthyroid patients with subacute thyroiditis

Background: Hyperthyroidism, as well as systemic inflammation, are associated with a higher incidence and complications of cardiovascular disease. Both in Graves’ disease and subacute thyroiditis, patients are hyperthyroid. However, in Graves’ disease, there is an autoimmune process in the thyroid, and in subacute thyroiditis, hyperthyroidism is accompanied by systemic inflammation. It is not known if the rate of cardiovascular complications is higher in the course of Graves’ disease or subacute thyroiditis.. Methods: We performed a retrospective study of all hyperthyroid patients newly diagnosed with Graves’ disease or subacute thyroiditis between January 1st 2018 and December 31st 2021 at the Department of Nuclear Medicine, University Medical Centre Ljubljana. Cardiovascular complications in the period 3 months before or after diagnosis were registered. Values are expressed as mean (SD).. Results: The sample analysis included 1028 patients (247 with subacute thyroiditis, 781 with Graves’ disease). The two groups did not significantly differ by sex, age, and body mass index. A cardiovascular complication was registered in 78 patients; the incidence was significantly higher in Graves’ disease than in subacute thyroiditis (74 vs. 4, p<0.001). Compared to patients with subacute thyroiditis, patients with Graves’ disease had significantly lower TSH: 0.010 (0.006) vs. 0.024 (0.044) mIU/L (p<0.001), higher free T4: 44.1 (26.6) vs. 37.0 (14.7) pmol/L (p<0.001), higher incidence of diabetes: 4.3 vs. 0.4% (p=0.001), arterial hypertension: 12.2 vs. 5.7% (p=0.004) and smoking: 26.7 vs. 8.7% (p<0.001). In a logistic regression model, a significantly higher likelihood for cardiovascular complications was found in Graves’ disease vs. subacute thyroiditis (odds ratio 5.82, p=0.001), in patients with arterial hypertension (odds ratio 2.83, p=0.002), and in those with higher body mass index (odds ratio 0.92, p=0.043).. Conclusion: We report a higher incidence of cardiovascular complications in hyperthyroid patients with Graves’ disease in comparison to hyperthyroid patients with subacute thyroiditis. Patients with Graves’ disease were more severely hyperthyroid and had more adverse cardiovascular risk factors.

ECMO in the Management of Noncardiogenic Pulmonary Edema with Increased Inflammatory Reaction After Cardiac Surgery: A Case Report and Literature Review

Noncardiogenic pulmonary edema after cardiac surgery is a rare but severe complication. The etiology remains poorly understood; however, the issue may arise from multiple sources. Possible causes include a significant inflammatory response or an autoimmune process. Pulmonary edema resulting from noncardiac etiologies can necessitate extracorporeal membrane oxygenation (ECMO) because most of the cases present a substantial volume of fluid expelled from the lungs and the medical team must manage the inability to achieve effective ventilation. A 64-year-old patient with known heart disease was admitted to our clinic with acute pulmonary edema. His medical history included Barlow’s disease, severe mitral regurgitation (IIP2), moderate–severe tricuspid regurgitation, and moderate pulmonary hypertension. The patient had a coronary angiography performed in a prior hospitalization before the surgical intervention which indicated the absence of coronary lesions. Preoperative screening (nasal, pharyngeal exudate, inguinal pouch culture, and urine culture) was negative, with no active dental infections. The patient was stabilized, and 14 days post-admission, mitral and tricuspid valve repair was performed via a thoracoscopic approach. After being admitted to intensive care post-surgery, the patient quickly developed pulmonary edema, producing a large volume (4.5 L) of yellow secretions through the intubation tube followed by hemodynamic instability necessitating high doses of medications to support circulation but no cardiorespiratory arrest. Due to his worsening condition, the patient was urgently taken back to the operating room, where veno-venous extracorporeal membrane oxygenation (VV-ECMO) was initiated to support oxygenation and stabilize the patient.

Transcriptome-based characterization of 3’2’-cGAMP signaling mediated immune responses

Cyclic dinucleotides (CDNs) are critical adjuvants in antiviral vaccines and cancer immunotherapy, primarily through the activation of the cGAS-STING signaling pathway. Evaluating the immune responses triggered by CDNs is essential for the development of effective adjuvants. In this study, we performed a comparative transcriptome analysis to characterize the immune responses elicited by the recently identified nuclease-resistant Drosophila and bacterial CDN, 3’2’-cGAMP, in mammalian immune cells. We detected a robust induction of innate immune gene signature following 3’2’-cGAMP stimulation in digitonin-permeabilized mouse primary macrophages, comparable to the response observed with the canonical mammalian CDN, 2’3’-cGAMP. STING deficiency remarkably reduced 3’2’-cGAMP-induced phosphorylation of TBK1 and IRF3 and the induction of IFN-β, indicating that 3’2’-cGAMP signaling-mediated immune responses were mainly STING dependent. In comparison to 2’3’-cGAMP signaling, 3’2’-cGAMP signaling preferentially elicited many STING-dependent genes involved in transcription and nucleosome positioning and assembly in the nucleus, which are likely associated with several enriched pathways, including cellular senescence, HDACs deacetylate histones, and epigenetic regulation of gene expression. The integrative analysis further revealed that 3’2’-cGAMP signaling preferentially induced genes were associated with autoimmune disease-related processes, suggesting a potential side effect that requires monitoring when used as an adjuvant. In conclusion, this study provides the first transcriptional landscape of 3’2’-cGAMP signaling in mammals and reveals the immune response characteristics and potential side effects mediated by 3’2’-cGAMP signaling. These findings may aid in the development of 3’2’-cGAMP-based adjuvants for antiviral vaccines and cancer immunotherapy.

The Clinical Significance of Interstitial Pneumonia with Autoimmune Features in Cryptogenic Organizing Pneumonia: A Prospective Multicenter Observational Study.

Background: There are cases of idiopathic interstitial pneumonias (IIPs) that do not meet the diagnostic criteria for connective tissue disease but have clinical features suggestive of autoimmune process. Interstitial pneumonia with autoimmune features (IPAF) was recently proposed as a research concept for these patients. Although several prospective studies on IPAF have been conducted, its clinical significance in cryptogenic organizing pneumonia (COP) remains unclear. Methods: Patients aged ≥20 years with suspected COP were prospectively enrolled between June 2018 and December 2022. Among the enrolled patients, those diagnosed with COP based on computed tomography (CT) and bronchoalveolar lavage (BAL) findings were compared between the IPAF and non-IPAF groups. Results: A total of 56 patients were enrolled in this study. Of these, 30 were diagnosed with COP and included in the analysis. Clinical and serological features were positive in two and six patients, respectively. Each feature was exclusive, and eight patients (26.7%) were diagnosed with IPAF. There were no differences between the IPAF and non-IPAF groups in terms of clinical features, including BAL findings, laboratory data, CT findings, and clinical course. During the one-year follow-up period, the frequency of COP exacerbation did not differ between the IPAF and non-IPAF groups, and no cases of systemic autoimmune disease or death occurred in either group. Conclusions: The COP characteristics of the IPAF and non-IPAF groups are similar in all aspects, and distinguishing between the two groups may be of little significance.

Angiotensin type-1 receptor autoantibodies promote alpha-synuclein aggregation in dopaminergic neurons.

Angiotensin, through its type-1 receptor (AT1), is a major inducer of inflammation and oxidative stress, contributing to several diseases. Autoimmune processes have been involved in neurodegeneration, including Parkinson's disease (PD). AT1 autoantibodies (AT1-AA) enhance neurodegeneration and PD, which was related to increased neuronal oxidative stress and neuroinflammation. However, the effect of AT1-AA on α-synuclein aggregation, a major factor in PD progression, has not been studied. In cultures of dopaminergic neurons, we observed that AT1-AA promote aggregation of α-synuclein, as AT1-AA upregulated major mechanisms involved in the α-synuclein aggregation process such as NADPH-oxidase activation and intracellular calcium raising. The results further support the role of AT1 receptors in dopaminergic neuron degeneration, and several recent clinical studies observing the neuroprotective effects of AT1 receptor blockers.

Efficacy and safety of oral tofacitinib in vitiligo and its variants: A retrospective case series

Background: Vitiligo is a chronic inflammatory skin disorder characterized by patchy depigmentation due to melanocyte loss, often leading to psychiatric morbidities. Emerging therapies like JAK inhibitors, like tofacitinib, target the autoimmune process underlying vitiligo by inhibiting the JAK-STAT pathway, potentially offering more effective and sustained repigmentation with fewer side effects. There is limited data on the dosing, efficacy, and safety of tofacitinib in treating vitiligo, particularly within the Indian population, beyond a few case reports and clinical trials. Aim: This study aims to retrospectively analyze the safety and efficacy of tofacitinib in vitiligo patients. Methods: This retrospective case series reviewed oral tofacitinib use in vitiligo patients from the Department of Dermatology, Cutis Hospital, Bengaluru, India, between January 2020 and August 2022. Data were collected on patient demographics, treatment history, clinical assessments, and laboratory investigations. Tofacitinib was administered at 5 mg twice daily, often combined with NB-UVB phototherapy. Results: The study included 20 patients (11 males and 9 females) aged 24–57 years. Disease duration varied from 1 to 20 years. Nine patients had more than 25% reduction in Vitiligo Area Severity Index when compared to baseline. No significant side effects were recorded, although some patients showed an increase in cholesterol and triglycerides. Conclusion: Tofacitinib shows promise as a targeted therapy for vitiligo with a favorable safety profile. Despite limited data, initial results indicate significant efficacy, particularly when combined with phototherapy. Further research is needed to validate these findings, especially in the Indian population, to establish comprehensive treatment guidelines for JAK inhibitors in vitiligo.

Trained immunity in the bone marrow: Hub of autoimmunity

An inappropriate induction of trained immunity in the bone marrow progenitors of immune cells has been described to underlie chronic inflammatory processes. Mills and colleagues' recently published paper in Cell Stem Cell shows that maladaptive trained immunity drives inflammation in autoimmune processes,1 opening a new area of research in autoimmunity.

Prevalence of co-existing autoimmune and autoinflammatory diseases in vitiligo: a survey-based study from Egypt.

The exact cause of vitiligo is still unknown. Genetic factors, self-destruction of melanocytes, the autoimmune process, and oxidative stress all can contribute to the pathogenesis of vitiligo. The aim of this study was to figure out the frequency of coexisting autoimmune and autoinflammatory diseases (AIIDs) in Egyptian patients with vitiligo and identify the associated risk factors. Egyptian children and adults with vitiligo and their parents were asked to answer a web-based survey. The survey consisted of multiple questions centered around demographic, clinical, and therapeutic data. The vitiligo disease activity (VIDA) score was evaluated for all the patients. Patients were also asked about the presence of co-existing AIIDs. There was a total of 294 participants, mostly females (54.8%), with a median age of 35 years and a median disease duration of 9 years. Nearly 27% had at least one AIID. The most common associated AIIDs were autoimmune thyroid disease (47 patients, 16%), followed by alopecia areata (14 patients,4.8%), then psoriasis and rheumatoid arthritis (11 patients, 3.7%). Univariate regression analysis revealed that age (OR 1.02, P = 0.036), female gender (OR 2.2, P = 0.004), disease duration (OR 1.04, P < 0.001), affected body surface area (OR 1.7, P = 0.048), and family history of AIIDs (OR 2.7, P < 0.001) were predictors for the presence of AIIDs in patients with vitiligo. AIIDs are prevalent among vitiligo patients. Age, female gender, and family history of AIIDs are the main predictors of the presence of AIIDs in vitiligo patients.

P20 Persistent anti-PR3 ANCA positivity in patient with extrapulmonary tuberculosis

Abstract Introduction Granulomatosis with polyangiitis (GPA) and tuberculosis (TB) are both granulomatous disease which can have similar clinical manifestations and organ involvement. This report discusses a case of such overlapping clinical presentation and anti-neutrophil cytoplasmic antibodies (ANCA) positivity, leading to diagnostic uncertainty. Case description A 40-year-old female who lived in sub-Saharan Africa until two years ago presented with a two month history of general malaise, significant weight loss, severe anorexia, diarrhoea, vomiting and nausea. She had no night sweats, blood in stool, abdominal pain, respiratory or cardiac symptoms, sino-nasal symptoms, rashes or neurological features. On examination, she appeared severely malnourished. Blood tests revealed microcytic anaemia (Hb 83 g/l, MCV 69fl), thrombocytosis, hypoalbuminemia (15 g/l), CRP 26 mg/l, elevated procalcitonin (1.46 ug/l), elevated LDH 263U/l. She had a positive double-stranded DNA and anti-cardiolipin IgM. ANCA was moderately positive with an anti-PR3 titre of 78 U/ml. Computerised tomography (CT) chest to pelvis revealed widespread necrotic lymphadenopathy, bilateral pulmonary emboli with infarcts, pancolitis and non-specific gall bladder thickening. Endoscopy revealed inflamed featureless colon with no microscopic granulomata. Acid-fast bacilli were isolated on endobronchial ultrasound guided biopsy of the necrotic nodes leading to confirmation of the diagnosis of extrapulmonary disseminated tuberculosis. Clinical improvement and improvement in CRP and anti-PR3 titre (48 U/ml) were seen following two weeks of anti-tuberculous treatment and a weaning course of steroids for colitis. Discussion Often GPA and tuberculosis can have similar presentations including lung and gastrointestinal involvement along with lymphadenopathy. This case demonstrates how ANCA and PR3 positivity can also be a common feature in these two conditions. Correct diagnosis is crucial in preventing harm to the patient as a diagnosis of GPA would require prompt and aggressive immunosuppression which may result in disseminated mycobacterial infection in the case of misdiagnosis; similarly, anti-mycobacterial therapy is unlikely control systemic GPA. In our patient, although the enteritis, general malaise and weight loss can be features of vasculitis and tuberculosis, careful history suggested no convincing other features of GPA, including the absence of ear, nose, throat, skin, neurological or renal involvement. The social history yielded migration from sub-Saharan Africa where tuberculosis is much more prevalent. A useful distinguishing biochemical test was the elevated procalcitonin which points towards a bacterial infection rather than an autoimmune process. Ultimate conclusive evidence of mycobacterial infection requires either positive acid-fast bacilli on staining or culture; lymph node biopsy allowed us to promptly and correctly diagnose this patient in the absence of sputum or pulmonary tuberculosis. Initiation of anti-tuberculous treatment rapidly settled this patient’s symptoms with a falling CRP. This case report highlights the fact that tuberculosis can mimic ANCA-associated vasculitis with positive anti-PR3 antibodies. In such cases, careful history taking, appropriate imaging and positive acid fast bacilli on staining or culture from sputum or tissue are important for prompt diagnosis and treatment. Both disseminated tuberculosis and systemic GPA can be rapidly progressive and severe if untreated. Although literature described the co-existence of both conditions, this is very rare. Correct diagnosis is key in initiation of the widely different treatment strategies, with the treatment for GPA potentially causing harm in disseminated tuberculosis. Key learning points • ANCA positivity in tuberculosis has been documented in the literature and positive anti-PR3 cannot be used solely to diagnose GPA. Therefore, a thorough history, examination, imaging and tissue examination, including tuberculosis culture and acid-fast staining, are recommended.

Human body resistance dynamics in the post-covid period

The issue of the state of specific and nonspecific resistance in the post-COVID period and the possible consequences of COVID-19 remains poorly understood. A clinical and laboratory examination of 124 patients was conducted at various time points after COVID-19 infection. 62 patients recovered completely and 62 had post-COVID syndrome. The leukocyte count and leukogram were evaluated in all patients. Immunogram parameters were additionally evaluated in patients with post-COVID syndrome. The results showed that, regardless of post-COVID syndrome, leukocyte count is lower in all patients within six months after COVID-19 infection than in unaffected subjects. The absolute neutrophil count is restored only 12 months later. In the presence of post-COVID syndrome, the absolute number of CD3+, CD4+and CD19+lymphocytes was lower than in healthy people. At the same time, 3 to 15 months after that, IgA titer in patients with PCS was significantly lower and that of for total IgM and IgG was higher without any clinical or laboratory signs of inflammation. The total blood IgE level was significantly higher and increased by the end of the observation period. A decreased activity of nonspecific protection, as well as indicators of cellular and humoral immunity in patients with post-COVID syndrome is accompanied by higher rate of viral and bacterial infections of various localization. Whereas during the first period an increase in total blood ID is not accompanied by clinical signs of atopy, then 6 months later the frequency of allergy increases. During the same period, cases of a joint syndrome revealed as arthralgia or progressive joint destruction become more frequent. Atopic manifestations are often combined with joint syndrome. Thus, after a COVID-19 infection, a low long-term level of nonspecific protection remains in vivo. In patients with post-COVID syndrome, low nonspecific and specific body resistance is manifested by viral and bacterial infections of the mucous membranes and skin. An imbalance in the immune system contributes to developing allergic and autoimmune processes.

Autoimmune thyroiditis: an update on treatment possibilities.

Autoimmune thyroiditis (AIT) is due to an autoimmune process that destroys thyrocytes, leading to hormonal disorders. AIT is more common in women, and the aetiology is multifactorial. The destruction of thyroid cells may release free thyroid hormones into the bloodstream, causing hyperthyroid symptoms. With further destruction of thyroid cells, patients develop euthyroidism and eventually chronic hypothyroidism. The diagnosis of AIT is based on clinical symptoms, positive anti-thyroid antibodies, ultrasound, and histological features. The main goal of treatment is correcting hormonal disorders and achieving euthyroidism. Treatment of AIT involves replacing thyroid hormone deficiency with the use of synthetic hormones. Prophylactic levothyroxine (L-T4) treatment of euthyroid patients with AIT may reduce both serological and cellular markers of autoimmunisation. Attention should be paid to the starting dose of L-T4, potential drug interactions, and drug formulation. A follow-up should be planned to determine the optimal dose. The authors highlighted that a healthy lifestyle and supplementing selected vitamins and microelements appropriately are essential. In selected clinical conditions, thyroidectomy should be considered. There are also alternative therapeutic strategies, such as herbal medicine and acupuncture, but their effectiveness has yet to be conclusively confirmed in research studies. Monitoring the thyroid gland enlargement and the possibility of developing nodular goitre is integral to patient care over AIT patients. In conclusion, treating AIT is complex, involving thyroid hormone replacement therapy, taking care of a healthy diet and lifestyle, and proper supplementation. It requires an individual approach. Regular follow-up is necessary to control the disease and minimise its effects.

Prevalence Of Metabolic Syndrome In Vitiligo: A Cross-sectional Study

Introduction Vitiligo is a common acquired hypomelanotic disorder of the skin and is characterized by depigmented macules and patches that can appear anywhere on the skin. In pathogenesis, the researchers have suggested an interplay of multiple factors such as genetic, neural, oxidant-antioxidant, biochemical, minerals, and autoimmune processes in the induction of vitiligo. Metabolic syndrome (MetS), also known as Syndrome X is a pathological condition typically characterized by the combination of various interrelated metabolic disorders that include abdominal obesity, impaired glucose tolerance, dyslipidemia, and hypertension. The linkage of skin diseases and MetS is due to ongoing chronic inflammation due to elevated pro-inflammatory cytokines, imbalance between reactive oxygen species and antioxidants, and hormonal abnormalities mostly insulin resistance. Methodology This cross-sectional study included patients diagnosed with vitiligo and above 16 years of age. All the patients were sent for analysis of fasting lipid profile and fasting blood glucose level. The waist circumference was measured at the mid-point between the lower border of the rib cage and the iliac crest with a flexible inch tape. The blood pressure was taken in a sitting posture after 10 minutes of rest. The data was collected using a preformed proforma. Results Of the 70 patients, the majority (N=38) were male. The mean age was 37 years with a range from 16 to 79 years. The mean age of male patients was 39.87 ± 17.24 years and female patients was 33.59 ± 13.58 years. The most common clinical type of vitiligo was generalized vitiligo (48.6%) followed by focal (18.6%) and segmental (15.7%). The metabolic syndrome was present in 26 patients (37.1%). The patient with generalized vitiligo had maximum prevalence (n=10) followed by acrofacial vitiligo (n=6). Conclusion This study found a high prevalence of metabolic syndrome and its components in patients with vitiligo. Therefore, vitiligo patients need to be screened for metabolic syndrome to prevent unforeseen complications.

Physiological and pathogenic T cell autoreactivity converge in type 1 diabetes

Autoimmune diseases result from autoantigen-mediated activation of adaptive immunity; intriguingly, autoantigen-specific T cells are also present in healthy donors. An assessment of dynamic changes of this autoreactive repertoire in both health and disease is thus warranted. Here we investigate the physiological versus pathogenic autoreactive processes in the context of Type 1 diabetes (T1D) and one of its landmark autoantigens, glutamic acid decarboxylase 65 (GAD65). Using single cell gene expression profiling and tandem T cell receptor (TCR) sequencing, we find that GAD65-specific true naïve cells are present in both health and disease, with GAD65-specific effector and memory responses showing similar ratios in healthy donors and patients. Deeper assessment of phenotype and TCR repertoire uncover differential features in GAD65-specific TCRs, including lower clonal sizes of healthy donor-derived clonotypes in patients. We thus propose a model whereby physiological autoimmunity against GAD65 is needed during early life, and that alterations of these physiological autoimmune processes in predisposed individuals trigger overt Type 1 diabetes.

Thyroid Function in the Time of COVID-19: A Systematic Review of Disease Progression and Vaccination Effect

Objectives: This systematic review sought to address three key questions: (1) what differences in abnormal thyroid function test results are observed between COVID-19 patients and healthy individuals? (2) How does the severity of COVID-19 infection influence the development of thyroid dysfunction? (3) What impact do COVID-19 vaccines have on thyroid function and autoimmune processes? Methods: A literature search was conducted in PubMed, Web of Science, and Scopus from December 2019 to April 2023 to identify studies on thyroid dysfunction in COVID-19 patients without pre-existing thyroid conditions. The search focused on observational and case-control studies. Results: The literature search yielded 329 reports, from which duplicates and unrelated publications were excluded. Ultimately, 21 studies met the inclusion criteria and were selected for review. A second literature search yielded 605 reports, from which 5 studies were selected for inclusion in the systematic review. Conclusions: The findings suggest that SARS-CoV-2 infection can induce transient and reversible thyroid dysfunction, possibly through direct viral effects on the thyroid gland or via indirect immune-mediated mechanisms. Clinicians should be mindful of the potential, albeit rare, thyroid-related adverse effects of COVID-19 vaccines and monitor thyroid function, particularly in high-risk individuals.

Kikuchi lymphadenitis, a rare case: an overview of its clinical presentation, diagnostic challenges, and therapeutic approaches

Kikuchi-Fujimoto Disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, self-limiting condition typically presenting with lymphadenopathy and fever. The etiology remains unclear, but it is thought to be associated with viral infections and autoimmune processes. We report a case of a female who presented with cervical lymphadenopathy. An excisional biopsy of the lymph node was performed, showing characteristic histopathological features of KFD. Based on the clinical presentation and histopathological findings, a diagnosis of Kikuchi-Fujimoto disease was made. The patient was managed with supportive care, including antipyretics and Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). No antibiotics or corticosteroids were administered. The patient's symptoms gradually resolved over a period. Follow-up at three months revealed the resolution of symptoms with no recurrence. The patient remained asymptomatic at subsequent visits. KFD should be considered in young patients presenting with fever and lymphadenopathy. Diagnosis is confirmed through lymph node biopsy demonstrating characteristic histopathological features. The disease typically follows a benign course with spontaneous resolution, and management is primarily supportive.

Modern Russian drugs for the treatment of neurodegenerative diseases

Neurodegenerative diseases are characterized by progressive death of nerve cells of certain types with concomitant atrophy of the corresponding parts of the spinal cord or brain, which is symptomatically manifested by severe neurological and cognitive impairment. These diseases can manifest at any age and be caused by both genetic predisposition and inflammatory and autoimmune processes. Diseases of this group are a common cause of disability and mortality. Thus, the development of new effective domestic drugs for their treatment is an important task for the healthcare system of the Russian Federation. In this review is devoted to the analysis of Russian original and bioanalog organic and genetically engineered drugs for the treatment of neurodegenerative diseases that have been registered in recent years or are currently undergoing clinical trials in Russia.

Decoding mutational hotspots in human disease through the gene modules governing thymic regulatory T cells.

Computational strategies to extract meaningful biological information from multiomics data are in great demand for effective clinical use, particularly in complex immune-mediated disorders. Regulatory T cells (Tregs) are essential for immune homeostasis and self-tolerance, controlling inflammatory and autoimmune processes in many diseases with a multigenic basis. Here, we quantify the Transcription Factor (TF) differential occupancy landscape to uncover the Gene Regulatory Modules governing lineage-committed Tregs in the human thymus, and show that it can be used as a tool to prioritise variants in complex diseases. We combined RNA-seq and ATAC-seq and generated a matrix of differential TF binding to genes differentially expressed in Tregs, in contrast to their counterpart conventional CD4 single-positive thymocytes. The gene loci of both established and novel genetic interactions uncovered by the Gene Regulatory Modules were significantly enriched in rare variants carried by patients with common variable immunodeficiency, here used as a model of polygenic-based disease with severe inflammatory and autoimmune manifestations. The Gene Regulatory Modules controlling the Treg signature can, therefore, be a valuable resource for variant classification, and to uncover new therapeutic targets. Overall, our strategy can also be applied in other biological processes of interest to decipher mutational hotspots in individual genomes.

Morphometric evaluation of facial and vestibulocochlear nerves using magnetic resonance imaging in patients with Menière's disease.

Menière's disease (MD) is a condition of unknown etiology, involving genetic predisposition, autoimmune processes, viral infections, cellular apoptosis, and oxidative stress. This study aimed to investigate potential differences in the VIIth and VIIIth cranial nerves in MD patients using Hydrops-MRI (FLAIR) for morphometric evaluations. Using a 3T MRI scanner, constructive-interference-in-steady-state (CISS) and 3D-FLAIR-inversionrecovery (FLAIR) sequences were acquired. We evaluated the morphometrics of the VIIth and VIIIth cranial nerves from the cerebellopontine angle to the internal auditory canal fundus, comparing the non-affected and affected sides. Furthermore, we examined the findings in relation to symptom duration and evaluated feasibility of FLAIR-imaging in morphometry of cranial nerves. A total of 53 MD patients with unilateral symptoms were included. After statistical analysis, no significant differences were found regarding morphometric changes in the affected side compared to the non-affected side of the VIIth and VIIIth cranial nerves. There was also no significant difference between morphometric evaluations of patients with different symptom durations. The morphometric evaluation using Hydrops-MRI-Sequences (FLAIR) showed no significant difference compared to established morphometric highly T2-weighted imaging (CISS). Our data found no differences in nerve morphometry between clinically non-affected and affected sides in unilateral MD patients, nor any correlation with symptom duration. This contrasts with previous findings of correlations between clinical features and endolymphatic hydrops. A disease process starting before clinical symptom onset could be a possible explanation. Morphometric evaluation of brain nerves using Hydrops-MRI-Sequences is practical and provides similar results to T2-weighted imaging, improving patient comfort and reducing MRI scan time. CN = cochlear nerve; CPA = cerebellopontine angle; CSA = cross-sectional area; FN = facial nerve; IAC = internal auditory canal; IVN = inferior vestibular nerve; LD = long diameter; MD = Menière's disease; SD = short diameter; SVN = superior vestibular nerve.

Late-onset primary muscle diseases mimicking sarcopenia.

Sarcopenia is an age-related loss of skeletal muscle mass, strength, and function that causes various health problems. In contrast, late-onset primary myopathies, which occur in the older population, are caused by a variety of factors, including genetic mutations, autoimmune processes, and metabolic abnormalities. Although sarcopenia and primary myopathy are two distinct disease processes, their symptoms can overlap, making differentiation challenging. The diagnostic criteria for sarcopenia have evolved over time, and various criteria have been proposed by expert groups. Late-onset primary muscle diseases such as inclusion body myositis, sporadic late-onset nemaline myopathy, muscular dystrophies, distal myopathies, myofibrillar myopathies, metabolic myopathies, and mitochondrial myopathies share common pathogenic mechanisms with sarcopenia, further complicating the diagnostic process. Appropriate clinical evaluation, including detailed history-taking, physical examination, and diagnostic testing, is essential for accurate diagnosis and management. Treatment approaches, including exercise, nutritional support, and disease-specific therapies, must be tailored to the characteristics of each disease. Despite these differences, sarcopenia and primary myopathies require careful consideration in the clinical setting for proper diagnosis and management. This review outlines the evolution of diagnostic criteria and diagnostic items for sarcopenia, late-onset primary myopathies that should be differentiated from sarcopenia, common pathomechanisms, and diagnostic algorithms to properly differentiate primary myopathies. Geriatr Gerontol Int 2024; 24: 1099-1110.

Microbiological bases of obsessive‑compulsive disorder - the role of viruses, bacteria, and parasites in the onset and progression of OCD.

Obsessive‑compulsive disorder (OCD) is a current topic of discussion nowadays. OCD presents a variety of different etiologies including environmental, viral, cognitive, or genetic aspects. In this article, we focused on the possible correlation between various infectious diseases as well as generally the relationship between viruses, bacteria, and parasites, and an increased OCD risk. In this narrative review, we analyzed different types of articles found on PubMed, Google Scholar, and Scopus, as well as the articles of the National Institute of Mental Health. Searching criteria included articles from 1991 till the end of November, research involving human and animal patients (including monkeys and rats), and research published in English. Research showed a relationship between Herpes simplex virus, Rubella virus, Human immunodeficiency virus, Borna disease virus, Mycoplasma pneumoniae, Toxoplasma gondii, streptococcal infections, as well as gut microbiota and increased OCD risk. The possible mechanisms of this relation include neuroinflammation, brain tissue damage, autoimmune processes, and impairments in neurotransmitter levels. Infections caused by Varicella zoster virus, Measles virus, Mumps virus, Epstein‑Barr virus, Cytomegalovirus, or Borrelia Burgdorferi may also contribute to the increased risk of OCD. Reports showed an increased frequency of OCD occurrence in a group of infected people compared to a healthy group. However, there is no evidence of the influence of Influenza virus, Coxsackie virus, Poliovirus, Parvovirus B19, Enterovirus 71, West Nile virus, Treponema Pallidum, or Toxocara infections on the OCD risk. There is a significant relationship between various infectious diseases and an increased OCD risk. However, further studies are crucial to discover the exact pathomechanisms of these correlations and the potential influence of other pathogens on the onset of OCD.