Manifestations Of Autoimmune Disease Research Articles

Plasmapheresis in the treatment of post-COVID syndrome in dermatology. Case report

The relevance of studying the impact of coronavirus infection on the development and course of autoimmune diseases is due to an increase in the incidence of COVID-19 infection, which is confirmed by reliable data from recent large-scale studies. The trigger mechanisms of autoimmune disorders, particularly those with dermatological manifestations, have been well studied. COVID-19 significantly increases not only the risk of manifestation of autoimmune diseases but also the transformation of a preexisting disorder into severe, atypical, and resistant to standard therapy forms. The article analyzes the data of patients with psoriasis treated in a day hospital from 2021 to 2023 at the affiliate of the Moscow Scientific and Practical Center of Dermatology, Venereology and Cosmetology “V.G. Korolenko Clinic” with exacerbation or onset of the disease reliably associated with a history of coronavirus infection. It is a clinically significant issue since there is a pathomorphosis of a typical pattern of exacerbations: the area of skin lesions increases, exudative and toxicoallergic components are manifested; psoriasis is torpid, which requires the development of individual algorithms for the treatment of patients with psoriasis and post-COVID syndrome, considering the mechanisms of this condition development. An essential aspect in the analysis of this sample of patients was the assessment of general somatic comorbidity, which requires a multidisciplinary approach in selecting therapy to comply with modern criteria for quality treatment, namely its maximum effectiveness and safety.

Unraveling The Genetics of Shared Clinical and Serological Manifestations in Systemic Inflammatory Autoimmune Diseases.

Systemic inflammatory autoimmune diseases (SIADs) such as systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS) and idiopathic inflammatory myopathies (myositis) are complex conditions characterized by shared circulating autoantibodies and clinical manifestations, including skin rashes, among others. This study aimed at elucidating the genetics underlying these common features. We performed targeted DNA sequencing of coding and regulatory regions from ~1,900 immune-related genes in a large SIAD cohort of 2,292 well-characterized Scandinavian patients with SLE, pSS and myositis, as well as 1,252 controls. A gene-based functionally-weighted genetic score for aggregate testing of all genetic variants, including rare variants, was complemented by in-silico functional analyses and in-vitro reporter experiments. Case-control association analysis detected known and potentially novel genetic loci in agreement with previous genetic and transcriptomics findings linked to the SIAD autoimmune background. Intriguingly, case-case comparisons between patient subgroups with and without specific autoantibodies revealed that the subgroups defined by ANA and anti-dsDNA antibodies have unique genetic profiles reflecting their heterogeneity. When focusing on clinical features, we overall showed that DUSP1 protective genetic variants lead to increased gene expression and potentially to anti-inflammatory effects on the SIAD-associated skin phenotype. This is consistent with recent genetic findings on eczema and with the previously reported downregulation of the MAPK signaling-related gene DUSP1 in other skin disorders. Together, this suggests common molecular mechanisms potentially underlying overlapping clinical manifestations shared among different disorders and informs clinical heterogeneity, which could be translated to improve disease diagnostic and treatment, also in more generalized disease frameworks.

Effect of DNA methylation at the CTLA4 gene on the clinical status of autoimmune thyroid diseases

The pathogenesis and manifestation of autoimmune thyroid diseases (AITDs), Graves' disease (GD), and Hashimoto's disease (HD) are associated with T cell activation. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays a crucial role in the regulation of T cell activation. DNA methylation levels of eight CpG sites in the CTLA4 gene and expression levels of soluble CTLA-4 were examined. Methylation levels of +22 CpG and CT60 CpG-SNPs in patients with GD and HD with the CT60 GG genotype were lower than those in control subjects. Methylation levels of the-15 CpG sites were lower in patients with intractable GD than those in GD patients in remission. These results suggest that demethylation of +22 CpG and CT60 CpG-SNPs may be associated with susceptibility to GD and HD in subjects with the CTLA4 CT60 GG genotype, and that demethylation of −15 CpG may be associated with the intractability of GD.

Cutaneous Langerhans cell histiocytosis and other systemic inflammatory or autoimmune disease manifestations in the setting of clonal hematopoiesis

Cutaneous Langerhans cell histiocytosis and other systemic inflammatory or autoimmune disease manifestations in the setting of clonal hematopoiesis

Registry of patients with autoimmune liver diseases in St. Petersburg: clinical and epidemiological data

BACKGROUND: The problem of autoimmune liver diseases, which include autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis and their overlap syndromes is an urgent problem of modern medicine. This is associated with an increase in the incidence and prevalence of these nosologies in different regions of the world. Absence of an established etiological factor, prolonged asymptomatic or low-symptomatic course, lack of pathognomonic clinical picture, imperfect diagnostic criteria, insufficient awareness of physicians lead to late diagnosis of autoimmune liver diseases and, accordingly, untimely initiation of treatment, which often reduces its effectiveness, affecting the further prognosis and survival rate for this group of patients. Patients with autoimmune liver diseases require long-term, often lifelong therapy and dispensary observation. Epidemiological registries along with autoimmune liver diseases registries, including various nosologies of autoimmune liver diseases, form an important database on the incidence, clinical features, development and course of the disease, variants of therapy and response to therapy, presence of extrahepatic manifestations as well as allow analysis of all data in dynamics. AIM: To analize data on various nosologies of autoimmune liver diseases, demographics, clinical symptoms, timing of the first symptoms, timing of diagnosis, and the nature of extrahepatic manifestations. MATERIALS AND METHODS: This article presents data from the autoimmune liver diseases Register of the North-West Hepatology Centre (North-West Autoimmune Liver Diseases Register) of the North-Western State Medical University named after I.I. Mechnikov. RESULTS: The study obtained data on the nosological structure, demographic characteristics, timing of diagnosis verification, clinical symptoms and extrahepatic manifestations of autoimmune liver diseases. CONCLUSIONS: Establishing registers of autoimmune liver diseases, providing information about patients with these diseases, will help to assess the effectiveness of examination and treatment methods, factors affecting the course and prognosis of the disease. Analysis of the data obtained will help to develop screening programs, diagnostic algorithms and differential diagnostics of autoimmune liver diseases, which, in turn, will facilitate the diagnostic process, shorten the time of diagnosis, make it possible to start therapy earlier and, consequently, improve the prognosis and survival rate for this group of patients.

E026 Severe odynophagia due to cricoarytenoid arthritis in a patient with rheumatoid arthritis and systemic lupus erythematosus

Abstract Background/Aims A 65-year-old man with a 20-year history of rheumatoid arthritis (RA) presented with dysphagia, odynophagia, polyarthralgia and significant weight loss. Methods - Results In addition to raised markers of inflammation, he was anti-nuclear antibody, anti-dsDNA antibody, anti-chromatin antibody and rheumatoid factor positive. He was initiated on 20mg once daily prednisolone but reported continued dysphagia and odynophagia. Computerised tomography (CT) of the neck revealed sclerosis at both cricoarytenoid joints with positron emission tomography (PET-CT) imaging identifying focal FDG uptake in the right hemiglottis projected over the posterior right true cord. Direct visualisation showed reduced mobility of the arytenoids with incomplete glottic closure in the absence of other abnormalities. He was diagnosed with cricoarytenoid (CA) joint arthritis on a background of RA and systemic lupus erythematosus overlap, with the resolution of his symptoms following intravenous methylprednisolone. Conclusion CA arthritis is an increasingly rare manifestation of autoimmune disease, and severe ongoing odynophagia an atypical presentation. This case highlights the need for continued awareness of laryngeal manifestations of autoimmune disease and demonstrates the benefit of PET-CT in cases where the diagnosis is uncertain or delayed. Disclosure J.S. Berry: None. J. Robinson: None. W. Ng: Consultancies; Expert advice in the area of Sjogren’s syndrome to GlaxoSmithKline, MedImmune, UCB, Abbvie, Roche, Eli Lilly, Takeda, Resolves Therapeutics, Sanofi, Novartis and BMS.

Hormones and B-cell development in health and autoimmunity.

The development of B cells into antibody-secreting plasma cells is central to the adaptive immune system as they induce protective and specific antibody responses against invading pathogens. Various studies have shown that, during this process, hormones can play important roles in the lymphopoiesis, activation, proliferation, and differentiation of B cells, and depending on the signal given by the receptor of each hormone, they can have a positive or negative effect. In autoimmune diseases, hormonal deregulation has been reported to be related to the survival, activation and/or differentiation of autoreactive clones of B cells, thus promoting the development of autoimmunity. Clinical manifestations of autoimmune diseases have been associated with estrogens, prolactin (PRL), and growth hormone (GH) levels. However, androgens, such as testosterone and progesterone (P4), could have a protective effect. The objective of this review is to highlight the links between different hormones and the immune response mediated by B cells in the etiopathogenesis of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). The data collected provide insights into the role of hormones in the cellular, molecular and/or epigenetic mechanisms that modulate the B-cell response in health and disease.

Preliminary Study on Total Glucoside of Peony (TGP) Administration in Organ-Specific Autoimmune Diseases at Prof. dr. R. D. Kandou Hospital, Indonesia

Autoimmune diseases are a diverse group of conditions characterized by immune disturbances that cause aberrant B cell and T cell reactivity to normal constituents of the host. These diseases can involve essentially any organ system and affect individuals of any age, with a much greater prevalence among women. Although certain mechanisms unite these conditions into a single category, the clinical manifestations of autoimmune disease are highly varied. This research is an original and interventional study. It is a preliminary with analytic observational. The design is “the one group pre-test – post-test design”. This study was conducted at RSUP Prof. dr. R. D. Kandou over a six-month period from July 2016 to December 2016. The study included patients diagnosed with Graves’ disease, Hashimoto’s disease, and aplastic anemia, who were diagnosed based on their medical history, physical examination, and diagnostic workups. This study also aimed to evaluate the improvement in clinical symptoms within the Aplastic Anemia group, tracking the number of complaints reported each week. Four patients were included in the study, each receiving individualized basic therapy.

Risk of uveitis in autoimmune diseases patients treated with hydroxychloroquine: A population-based retrospective cohort study.

Uveitis is a common manifestation of various autoimmune diseases and can lead to severe visual impairment. Hydroxychloroquine (HCQ) is an antimalarial drug that is also used to treat autoimmune diseases. The aim of this study was to investigate the association between HCQ use and the incidence of uveitis in patients with autoimmune diseases, as well as to identify potential risk factors for the development of uveitis in this study. We conducted a population-based cohort study using a nationwide database to investigate the incidence of uveitis in patients with autoimmune diseases who received HCQ treatment. We selected non-HCQ comparison cohort at a 1:1 ratio by propensity score matching on age, sex, index date, urbanization, income, comorbidities, and medications. The data were analyzed using Cox proportional hazards models, and propensity score matching (PSM) was used to reduce selection bias. Our study included 15 822 patients with autoimmune diseases. After 1:1 PSM, there were 4555 individuals in both the HCQ group (n = 4555) and the non-HCQ group (n = 4555). The multiple Cox proportional hazard regression analysis was used for the estimation of adjusted hazard ratios on uveitis. After PSM, the adjusted hazard ratio for the HCQ group was 0.74 (95% CI = 0.58-0.95). These findings suggest that HCQ may play a protective role in reducing the risk of uveitis in patients with autoimmune diseases, including rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus groups. The Kaplan-Meier survival curves also showed a significantly lower incidence of uveitis in the HCQ group (log-rank = 0.0229) after PSM. HCQ use is associated with a lower incidence of uveitis in patients with autoimmune diseases. Further studies are needed to confirm this association and to investigate the underlying mechanisms.

Newborns with congenital complete heart block: Advice for perinatal care providers.

Congenital complete heart block (CCHB) is a rare, but a potentially life-threatening manifestation of autoimmune diseases in neonates. Bradycardia in CCHB can be misdiagnosed as foetal distress in utero and thus precipitating a Caesarean section. We report a case series of three neonates with bradycardia without any electrolyte abnormalities and structurally normal hearts with favourable outcomes.

A follow-up study on factors affecting the recovery of patients with hypothyroidism in different selenium environments

BackgroundHypothyroidism is a major manifestation of autoimmune thyroid diseases (AITD). We previously reported that a low selenium (Se) status was linked to an elevated prevalence of thyroid diseases. We hypothesized that Se status may also influence the restoration of thyroid function. Thus, this study aimed to investigate the factors affecting the recovery of thyroid function in patients with (sub-)clinical hypothyroidism, with a specific focus on Se status.MethodsWe conducted a 6-year prospective cohort study comparing two counties with different Se concentrations. Demographic and disease data were collected from 1,190 individuals (549 Se-adequate and 641 Se-deficient) who completed a follow-up study in 2019. In addition, urinary iodine (I) levels, thyroid function, and serum and nail Se levels were measured. Logistic regression was used to investigate the relationship between Se deficiency and recovery of thyroid function.ResultsSex and smoking status was similar between the two counties studied. Thyroid function recovery rate was significantly higher in Se-deficient counties (46.0% vs. 30.6%, P = 0.008). In the multivariate analysis, our results show that female sex (odds ratio [OR] (95% confidence interval [CI]) = 1.875 (1.080–3.257), P = 0.026] and increasing age [OR (95%CI) = 1.028(1.007–1.049), P = 0.009] were associated with the recovery rate. Additionally, our study revealed that while Se status was significant in the univariate analysis, this association appeared to disappear in the multivariate analysis.ConclusionsFemale sex and increasing age have unfavorable effects on the recovery of thyroid function in patients over 30 years of age with (sub-) clinical hypothyroidism.

Autoantibodies profile in autoimmune liver diseases and chronic viral hepatitis

liver failure. Autoantibodies are confirmed to have significance in the early screening of AILD patients, especially in those who are asymptomatic before onset of clinical signs. This study aimed to assess levels of liver autoantibodies and their association with clinical manifestations of autoimmune liver diseases and chronic viral hepatitis (CVH) patients. This case-control study included 50 patients (case group of 25 patients with AILD and control group of 25 patients with CVH). They were investigated for presence of antibodies against LKM-1, AMA-M2, PML, M2-3E (BPO), gp210, Sp100, LC-1, Ro52 and SLA/LP using the line immune blot technique, and for the presence of antinuclear antibodies (ANA), as non-organ specific autoantibodies, using indirect immunofluorescence technique. Specific autoantibodies were detected in all AILD cases and some of their levels were significantly higher when compared with CVH group. Among AILD patients, 52% were positive for ANA, whereas 61.1% of chronic hepatitis C and 28.6% of chronic hepatitis B patients were positive for ANA with no significant difference (p=0.3). In conclusion, early diagnosis of autoimmune liver diseases has been linked to assessment of autoantibodies, allowing for prompt therapeutic intervention to stop the progression of liver cirrhosis and the accompanying complications.

MANIFESTATIONS OF OCULAR AUTOIMMUNE DISEASES - LITERATURE REVIEW

Ocular manifestations in autoimmune diseases are mainly related to the formation of a chronic inflammatory process in the body. This is caused by an error in the body's histocompatibility system, which results in the lymphocyte attacking its own cells, which the lymphocyte considers foreign. Various autoimmune diseases with ocular symptoms may have different inflammation-related pathophysiology, ranging from increased vascular permeability in diabetic retinopathy to lymphocytic pressure in the exocrine glands in Sjögren's syndrome. The inflammatory process in the eye tissues leads to symptoms such as pain, redness, photosensitivity, tearing and reduced visual acuity. One of the most common autoimmune diseases associated with ocular symptoms is systemic lupus erythematosus, in which 50% of patients experience ocular symptoms. Ocular manifestations may worsen or improve depending on disease activity. Ophthalmological examination is extremely important for patients with autoimmune diseases because it allows for the early detection and treatment of eye-related diseases, monitoring the side effects of medications taken, and identifying other related health problems.

Antibody therapies in cancer and autoimmune disease

Cancer and autoimmune diseases are gradually proven to be "two sides of the same coin". Many cancer patients develop manifestations of autoimmune diseases and rheumatism, especially those receiving immune checkpoint inhibitors. At the same time, patients with autoimmune diseases also have cancer combined, which may be related to chronic inflammation damage to DNA or clinical medication. Antibody therapies, pioneered by monoclonal antibody drugs, are now used extensively in the treatment of cancer and autoimmune diseases. The relationship between cancer and autoimmune diseases is gradually being discovered, and some antibody therapies have therapeutic effects on both types of diseases, perhaps because the two have common targets. In-depth study of the role of various targets in the occurrence and development of the two types of diseases, screen the common targets, and discover the antibody drugs that play an activation or inhibition role against the common targets, so as to achieve the effect of "same treatment for different diseases", which brings hope to patients with "cancer-autoimmune diseases". This paper discusses the relationship between the two types of diseases, summarizes the specific targets and corresponding diseases of some antibody therapies, and analyzes the current status of antibody therapy in the treatment of the two types of diseases, in order to explore the "dual therapy" potential of more antibody therapies in the future, and develop new targets and drugs.

Manifestations of systemic connective tissue diseases on the oral mucosa: a literature review

Annotation. Despite the modern high level of medical care, autoimmune connective tissue diseases cause a lot of questions among scientists and are a significant problem for society. At the same time, in the scientific works available today, little attention is paid to the manifestations of connective tissue diseases in the oral cavity and modern diagnostics of the main types of dental pathology in such patients, which would have great scientific and practical importance. Therefore, the purpose of the review article was to perform an analysis of the scientific literature regarding orofacial manifestations of autoimmune connective tissue diseases. When using the following databases: PubMed, Google Scholar, Scopus, Web of Science and various combinations of keywords and subject headings of MESH such as “oral manifestations”, “oral mucosal lesions”, “autoimmune diseases”, “rheumatic diseases”, “connective tissue diseases”, “systemic lupus erythematosus”, “rheumatoid arthritis”, “systemic sclerosis”, “Sjögren’s syndrome”, “dermatomyositis”, 40 articles were chosen, which corresponded to the purpose of the study. The search results indicate that there is a direct correlation between the duration of the main disease and the severity of oral symptoms. Pronounced hyposalivation and dryness of oral mucosa are the most similar common signs of autoimmune diseases, which contributes to functional disorders and diseases of oral cavity. Oral manifestations are quite often a side effect of the treatment of connective tissue diseases. The pathology of oral mucosa in autoimmune diseases remains not well-understood, so makes it difficult to clarify its pathogenesis in detail, that would allow for the development of justified measures of prevention and treatment.

Clinical manifestations of autoimmune rheumatic diseases in the larynx

Introduction. Autoimmune rheumatic diseases are attributed to a systemic process that develops in many organs, including the larynx. Complaints of impaired vocal function in patients with this pathology require a thorough clinical and endoscopic analysis.The purpose of the study. To determine the clinical-endoscopic changes of the larynx in patients with impaired vocal function in autoimmune rheumatic diseases..Materials and methods. 31 (100%) patients aged 25 to 84 (41 ± 15) years with autoimmune rheumatic diseases applied to the phoniatric department of the St. Petersburg Research Institute of ENT. There were 3 men (10%), 28 women (90%). All patients complained of impaired vocal function, 5 of the examined (16%) were also concerned about breathing disorders during exercise or at rest.Patients were grouped into three groups: systemic lupus erythematosus 4 (13%) people, systemic vasculitis 10 (32%) people, rheumatoid arthritis 17 (55%) people.Videolaryngoscopy, videolaryngostroboscopy, autofluorescence endoscopy, NBI – endoscopy (according to indications) were used to make the diagnosis.Results. The distribution of laryngeal pathology by nosological forms in patients with аutoimmune rheumatic diseases was as follows. The most numerous were groups with functional dysphonia of the hypotonic type 10 (32%) and bamboo nodules of 8 (26%) patients. Chronic laryngeal stenosis was diagnosed in 5 (16%), and chronic catarrhal laryngitis and soft nodules of the vocal folds in 3 (9.5%) people in each group (respectively). The smallest number of patients suffered from ulcerative necrotic changes of the larynx and pharynx – 2 (7%).Conclusion. Thus, laryngeal changes in аutoimmune rheumatic diseases had both specific manifestations and non-specific ones. The latter include functional dysphonia of the hypotonic type, chronic catarrhal laryngitis, soft nodules of the vocal folds. Bamboo nodules of the vocal folds, ulcerative necrotic diseases, chronic laryngeal stenosis (infiltrative and scarring) were specific for patients with аutoimmune rheumatic diseases.

Association of anti-Ro52 autoantibody with interstitial lung disease in autoimmune diseases: a systematic review and meta-analysis

ObjectivesInterstitial lung disease (ILD) is an important manifestation of autoimmune diseases that can lead to morbidity and mortality. Although several autoantibodies have been linked with ILD presentation and adverse outcomes,...

Study of Association of Chromosomal Region 1Q21-23 with Rheumatoid Arthritis and Their Correlation with Severity of Disease.

The understanding of the pathophysiology of rheumatoid arthritis (RA) has taken a major step forward with the research of new illness-related genes and further deciphering the involved molecular. Gene variants like human leukocyte antigen (HLA)-DRB1 and PTPN22 1858T act as individual risk factors for RA. It also serves as a risk factor for the rate of progression of joint destruction and clinical manifestations in autoimmune diseases like RA. The focus of this study is to find out the association of chromosomal region 1q21-23 with RA and its connection with disease severity using the disease activity score (DAS) and distribution frequency of the prevalent alleles of such genes in an already recruited group of patients/controls of India, specifically Northwest Rajasthan. This was a case-control study wherein every patient of RA aged 16 years and above diagnosed with RA as per the 2010 American College of Rheumatology (ACR) and the European League against Rheumatism (EULAR) revised criteria for RA in Outpatient Department (OPD) and Inpatient Department (IPD) patients were included. Blood samples of the study population were drawn at Sardar Patel Medical College (SPMC), Bikaner (rheumatology OPD), along with the cooperation of Birla Institute of Technology and Science (BITS), Hyderabad (Department of Biological Sciences) from July 2009 to January 2012. A total of 100 controls (without any previous history of disease) and 135 cases were selected considering inclusion and exclusion criteria. Clinical data along with laboratory parameters like complete blood count, serum electrolytes (sodium, potassium, calcium, and chlorine ions), blood sugar, blood urea with serum creatinine, lactate dehydrogenase (LDH) isoenzymes assay, serum glutamic-oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT) ratio, serum γ-glutamyl transferase (GGT) level, serum amylase, arterial blood gas (ABG), total serum proteins were evaluated and recorded from the patients. Our study showed control group has a mean age of 45.11 + 4.12 years. The case and control groups did not have significant differences in any of the clinical variables. 59% of cases show joint deformity. Allelic frequencies of the D1S498 polymorphism in cases were found significant in sizes 198, 204, 208, and 210, while it was found insignificant in sizes 192, 196, 200, 202, and 206. No correlation was found in allelic frequencies of the D1S318 polymorphism in cases and controls. Bigger cohort studies will allow better genomic elucidation of clinically defined intermediate phenotypes evaluated in RA patients by virtue of the autoimmune origin of the disease and its diverse symptoms in patients. Genetic-molecular studies can be a milestone for adopting effective personalized treatment for such progressively debilitating diseases. How to cite this article: Gauri LA, Meena MK, Singh U, et al. Study of Association of Chromosomal Region 1Q21-23 with Rheumatoid Arthritis and Their Correlation with Severity of Disease. J Assoc Physicians India 2023;71(9):28-32.

Endomyocardial substrate of ventricular arrhythmias in patients with autoimmune rheumatic diseases.

Delayed enhancement-magnetic resonance imaging (DE-MRI) has demonstrated that nonischemic cardiomyopathy is mainly characterized by intramural or epicardial fibrosis whereas global endomyocardial fibrosis suggests cardiac involvement in autoimmune rheumatic diseases or amyloidosis. Conduction disorders and sudden cardiac death are important manifestations of autoimmune rheumatic diseases with cardiac involvement but the substrates of ventricular arrhythmias in autoimmune rheumatic diseases have not been fully elucidated. 20 patients with autoimmune rheumatic diseases presenting with ventricular tachycardia (VT) (n = 11) or frequent ventricular extrasystoles (n = 9) underwent DE-MRI and/or endocardial electroanatomical mapping of the left ventricle (LV). Ten patients with autoimmune rheumatic diseases underwent VT ablation. Global endomyocardial fibrosis without myocardial thickening and unrelated to coronary territories was detected by DE-MRI or electroanatomical voltage mapping in 9 of 20 patients with autoimmune rheumatic diseases. In the other patients with autoimmune rheumatic diseases, limited regions of predominantly epicardial (n = 4) and intramyocardial (n = 5) fibrosis or only minimal fibrosis (n = 2) were found using DE-MRI. Endocardial low-amplitude diastolic potentials and pre-systolic Purkinje or fascicular potentials, mostly within fibrotic areas, were identified as the targets of successful VT ablation in 7 of 10 patients with autoimmune rheumatic diseases. Global endomyocardial fibrosis can be a tool to diagnose severe cardiac involvement in autoimmune rheumatic diseases and may serve as the substrate of ventricular arrhythmias in a substantial part of patients.

The Role of Adipsin, Complement Factor D, in the Pathogenesis of Graves' Orbitopathy.

Graves' orbitopathy (GO) is an orbital manifestation of autoimmune Graves' disease, and orbital fibroblast is considered a target cell, producing pro-inflammatory cytokines and/or differentiating into adipocytes. Adipose tissue has been focused on as an endocrine and inflammatory organ secreting adipokines. We investigated the pathogenic role of a specific adipokine, adipsin, known as complement factor D in Graves' orbital fibroblasts. The messenger RNA (mRNA) expression of multiple adipokines was investigated in adipose tissues harvested from GO and healthy subjects. Adipsin protein production was analyzed in primary cultured orbital fibroblasts under insulin growth factor (IGF)-1, CD40 ligand (CD40L) stimulation, and adipogenesis. The effect of blocking adipsin with small interfering RNA (siRNA) on pro-inflammatory cytokine production and adipogenesis was evaluated using quantitative real-time PCR, Western blot, and ELISA. Adipogenic differentiation was identified using Oil Red O staining. Adipsin gene expression was significantly elevated in GO tissue and increased after the stimulation of IGF-1 and CD40L, as well as adipocyte differentiation in GO cells. Silencing of adipsin suppressed IGF-1-induced IL-6, IL-8, COX2, ICAM-1, CCL2 gene expression, and IL-6 protein secretion. Adipsin suppression also attenuated adipocyte differentiation. Exogenous treatment of recombinant adipsin resulted in the activation of the Akt, ERK, p-38, and JNK signaling pathways. Adipsin, secreted by orbital fibroblasts, may play a distinct role in the pathogenesis of GO. Inhibition of adipsin ameliorated the production of pro-inflammatory cytokines and adipogenesis in orbital fibroblasts. Our study provides an in vitro basis suggesting adipsin as a potential therapeutic target for GO treatment.