Diffuse Connective Tissue Diseases Research Articles

Long noncoding nuclear enriched abundant transcript 1_2 is a promising biomarker for childhood‐onset systemic lupus erythematosus

ABSTRACTImportanceSystemic lupus erythematosus (SLE) is a diffuse connective tissue disease with complex clinical manifestations and prolonged course. The early diagnosis and condition monitoring of SLE are crucial to disease prognosis.ObjectiveTo assess the diagnostic value of long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) in childhood‐onset SLE (cSLE).MethodsFifty‐seven children diagnosed with SLE, 40 children diagnosed with juvenile idiopathic arthritis (JIA), and 40 healthy children were included. Peripheral blood samples from each patient were collected. A quantitative polymerase chain reaction was used to confirm the expression of lncNEAT1_1 and lncNEAT1_2 in peripheral blood. Associations among parameters were analyzed using the Mann‐Whitney U test or independent sample t‐test.ResultsThe expression of both lncNEAT1_1 and lncNEAT1_2 in patients with cSLE were significantly higher than that of healthy control and patients with JIA. Receiver operating characteristic curves revealed an area under the curve (AUC) of 0.633 (95% confidence interval [CI], 0.524–0.742; P = 0.024) for lncNEAT1_1. The AUC of lncNEAT1_2 was 0.812 (95% CI, 0.727–0.897; P < 0.0001) to discriminate individuals with cSLE from health control and children with JIA with a sensitivity of 0.622 and a specificity of 0.925. Moreover, lncNEAT1_2 expression was higher in patients with cSLE presenting with fever, lupus nephritis, elevated erythrocyte sedimentation rate, active disease activity, and decreased C3 level, compared with those without these conditions. However, no similar correlation was observed for lncNEAT1_1.InterpretationThe expression of lncNEAT1_2 was significantly elevated in children with SLE, especially those with fever, renal involvement, and low C3 levels. These findings suggest that lncNEAT1_2 may represent a potential biomarker for cSLE.

ОРГАНИЗУЮЩАЯСЯ ПНЕВМОНИЯ У ДЕТЕЙ: ЭПИДЕМИОЛОГИЯ, ЭТИОЛОГИЧЕСКАЯ СТРУКТУРА, КЛИНИЧЕСКАЯ И КОМПЬЮТЕРНО-ТОМОГРАФИЧЕСКАЯ СЕМИОТИКА, КОМОРБИДНОСТЬ И ТЕРАПИЯ

Organizing pneumonia (OP) is an interstitial lung disease (ILD), which is characterized by the proliferation of granulation tissue in the bronchioles and alveoli, and diagnosed on the basis of clinical history, morphological data, CT changes and response to glucocorticoid (GC) therapy. Information about OP in children is limited due to the insufficient number of cases described and observed. The purpose of this research was to establish the epidemiological characteristics, etiological structure, clinical and CT semiotics of OP in children, to characterize its comorbidity and therapy. Materials and methods used: 20 children aged 4 months to 17 years old with OP were observed in 2009-2023. The diagnosis was set based on the clinical and anamnestic data, the presence of specific CT patterns, positive clinical and radiological dynamics during GC therapy, and (in 2 cases) according to histological examination results. Results: the ratio of boys to girls was 1.8:1, most often OP was diagnosed in infants (40%) and young children (30%) with various comorbid diseases with a frequency of 0.012‰ in the structure of all hospitalized patients of a multidisciplinary hospital in Moscow (Russia) in 2014-2022 The reasons for the acute (80%) and subacute (20%) OP were respiratory infections (40%), aspiration (30%), diffuse connective tissue diseases (DCTD) (10%), in a single case the OP had developed as part of lung injury associated with vaping and electronic cigarettes (EVALI), 15% of patients had an idiopathic version of OP (cryptogenic OP). The clinical picture of OP was characterized by shortness of breath (100%), cough (90%), fever, rales/crepitus (65%), wheezing (45%); the chest CT scan (n=19) showed zones of consolidation (100%), including subpleural localization (84%), trapezoidal shadowing (27%), zones of “ground glass” (68%), reversed halo sign (32%). Therapy included GC (95%), azithromycin (40%), mechanical ventilation (40%), oxygen therapy (60%). Clinical and radiological improvement occurred in 18 (90%) children, and death occurred in 2 (10%) children. Conclusion: OP is a rare variant of ILD whose reasons in children can be respiratory infections, aspiration, DCTD, EVALI. The effectiveness of GC in the presence of characteristic symptoms and CT images confirms the diagnosis.

Evaluation of impact of new coronavirus infection on clinical course of rheumatic diseases in real clinical practice

Aim. To evaluate the effect of COVID-19 on the clinical course of immunoinflammatory rheumatic diseases (IRD).Material and methods. The clinical course of IRD was analyzed in 324 patients who underwent new coronavirus infection (NCI) from March 2020 to February 2021 and were treated at Clinical Rheumatology Hospital No. 25 (Saint-Petersburg, Russia) for exacerbation of the underlying disease.Results. The risk factors of severe COVID-19 course in IRD were: age older than 60 years, presence of comorbid conditions (IHD, CHD, COLD), use of glucocorticoids in dose more than 12.5 mg per day and erythrocyte sedimentation rate values ≥ 40 mm/h before development of NCI. The use of immunosuppressive therapy and biological therapy had no effect on the worsening of the course of the viral infection in patients with IRD. The development of post-covid syndrome (asthenia, dyspnea, weight loss, memory loss) was noted in ¼ of the patients. Post-covid articular syndrome was characterized by the formation of arthritis associated with viral infection in 3.6% of patients, transformation of undifferentiated arthritis (UDA) into specific nosological forms in 49.0% (more often into early rheumatoid arthritis, RA), and exacerbation of joint syndrome in 83.4% of patients with advanced stage RA. In patients with diffuse connective tissue disease (DCTD), a significant increase in immunological activity due to antinuclear antibodies (maximum 1: 163840) was noted. We present clinical cases of arthritis associated with viral infection and fatal outcome in a patient with systemic sclerosis and interstitial lung damage after COVID-19.Conclusions. In the cohort of patients with IRD observed at Clinical Rheumatology Hospital No. 25 (Saint-Petersburg, Russia) COVID-19 had a moderate to severe course in half of patients, initiated the development of pneumonic complications in 68.6% of patients, arthritis associated with viral infection in 3.6%, transformation of UDA into IRD in 49.0% of cases and exacerbation of the main disease in the great majority of patients. Patients with DCTD with interstitial lung damage have a high risk of adverse outcome of NCI, especially in cases of unstable course of the disease, pronounced immunosuppression and require special monitoring.The authors present their own clinical experience with the use of Alflutop in a comorbid patient with osteoarthritis and increased pain after undergoing CCI, which indicates its effectiveness and cardiovascular safety. An important practical advantage of Alflutop should be considered the absence of its effect on the parameters of hemocoagulation and the reduction in the need for NSAIDs, which reduces the risk of thrombotic complications characteristic of long-term COVID. A short course of Alflutop (ten intramuscular injections of 2.0 ml every other day) contributes to ease of use and increased adherence to therapy in patients with osteoarthritis.

Photosensitive dermatoses in paediatric practice

Photodermatoses represent a heterogeneous group of disorders characterized by the development of pathological skin reaction to solar radiation. The development or intensification of inflammatory skin reaction after exposure to ultraviolet or electromagnetic spectrum that is visible to the human eye is a distinctive feature of all photosensitive photodermatoses. Although photodermatoses are less common in children than in adults, they are often associated with genetic or congenital metabolic disorders, and may also point to diffuse connective tissue diseases. Paediatric photodermatoses are often the result of genetic or congenital metabolic disorders, and may also indicate diffuse connective tissue diseases. The epidemiological studies have showed that the global prevalence of photodermatoses diagnosed with photopatch tests is above or equal to 5.7%. The authors presented a modern classification of photosensitive dermatoses according to the etiological factor. The article provides up-to-date information about photosensitive dermatoses, including statistical epidemiological data, pathogenesis features, and also emphasis is placed on the issues of the quality of life of children and their parents. The authors described the clinical presentations of the most common paediatric photosensitive dermatoses and the basic principles of their therapy. Among topical glucocorticosteroids, methylprednisolone aceponate has proven itself in the treatment of paediatric photodermatoses as it has not only a pronounced anti-inflammatory effect, but also is easy-to-use. The timely diagnosis of paediatric photosensitivity will help to minimize the development of complications associated with delayed treatment and insufficient prevention (photoprotection).

HLA-DRB1 Polymorphisms and Rheumatologic Manifestations in Chronic Hepatitis C.

Hepatitis C has been associated with rheumatologic manifestations (HCV-related RM). Clinically, HCV-related RM may be indistinguishable from the symptoms that occur in diffuse connective tissue diseases (DCTD-related RM), making the differential diagnosis difficult. Host genetic factors, such as the Human Leukocyte Antigens (HLA) polymorphisms were associated with HCV infection, however, there are no studies that discriminate between HCVrelated RM and DCTD-related RM. This study focused on verifying associations between HLADRB1 and RM in patients with chronic hepatitis C, aiming to distinguish between DCTD-related RM and HCV-related RM. The participants were 152 individuals, of both sexes, aged between 18 and 80 years, and affected by chronic hepatitis C. The patients underwent rheumatologic physical examination and HLA-class II (HLA-DRB1) typing was performed by PCR-SSO (Polymerase Chain Reactionsequence Specific Oligonucleotides). A significant number of patients with rheumatologic complaints (73%) not attributed to other causes was observed. DRB1*08 allele seems to confer protection against RM in chronic hepatitis C. There is no susceptibility association between HLA-DRB1 alleles and RM. The absence of association between HLA-DRB1 and the rheumatologic manifestations studied suggests that the pathophysiological pathways of DCTD-related RM and HCV-related RM are distinct.

Association of Key Genes IFIT1 and IFIT3 with Immune Infiltration in Systemic Lupus Erythematosus

Systemic lupus erythematosus is a diffuse connective tissue disease mediated by autoimmunity and characterized by immune inflammation. The purpose of this study is to explore candidate key genes and immune cell infiltration involved in the pathogenesis of systemic lupus erythematosus. Intersection genes derived from differentially expressed genes between systemic lupus erythematosus patients and healthy individuals are identified by weighted gene co-expression network analysis of module genes were aimed for gene ontology functional enrichment analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis. The key candidate genes interferon induced protein with tetratricopeptide repeats 1 and interferon induced protein with tetratricopeptide repeats 3 were searched through the protein-protein interaction network. The cell-type identification by estimating relative subsets of ribonucleic acid transcripts arithmetic tool assessed the abundance of immune cells in samples from systemic lupus erythematosus patients. Enzymelinked immunosorbent assay confirmed the differential expression of candidate genes in serum samples from systemic lupus erythematosus patients and healthy controls. This study found that interferon induced protein with tetratricopeptide repeats 1 and interferon induced protein with tetratricopeptide repeats 3 may devote to the pathogenesis and development of systemic lupus erythematosus and can be used as prediction target genes of systemic lupus erythematosus. In addition, neutrophils and plasma cells were infiltrated more in systemic lupus erythematosus patients with high expression of interferon induced protein with tetratricopeptide repeats 1 and interferon induced protein with tetratricopeptide repeats 3. Interferon induced protein with tetratricopeptide repeats 1 and interferon induced protein with tetratricopeptide repeats 3 are important predictors for the diagnosis and treatment of systemic lupus erythematosus.

Bilateral pleural effusion: etiology, diagnostics

The problem of etiologic diagnosis of bilateral pleural effusions is important because of the relatively large number and variety of diseases accompanied by this syndrome, the complexity of diagnosis verification, and the frequent diagnostic errors. The aim of this review is to describe the spectrum of diseases causing bilateral pleural effusion and to consider a set of diagnostic measures to clarify the etiology of the process. Analysis of 60 literature sources showed that the most common causes of bilateral transudative pleural effusions are cardiac, hepatic, and renal insufficiency. Exudative bilateral pleural effusions are found in inflammatory processes in the pleura, including tuberculosis, and develop when inflammation is transmitted by contact or lymphohematogenous routes from the lungs or other organs. Bilateral localization of pleural effusion in tumor processes is observed in 5.7% of cases. Bilateral pleural effusion is seen in pulmonary embolism, diffuse connective tissue diseases, acute idiopathic pericarditis, postinfarction Dressler syndrome, after pericardotomy, and after pacemaker placement. It may be observed in such rare diseases as sarcoidosis, yellow nail syndrome, and Meigs syndrome, and may be induced by some drugs. Conclusion. The choice of therapeutic measures for bilateral pleural effusion is determined by an accurate etiological diagnosis of the underlying disease. The diagnosis should be based on the patient's clinical data and cytologic, microbiologic, and biochemical analysis of pleural fluid obtained by pleural puncture. In some cases, additional examination methods such as pleural biopsy, bronchoscopy, ultrasound, computed, magnetic resonance imaging of the chest and abdomen, and positron emission tomography are required.

Polymorphism of genes of immune-inflammatory response, thrombophilia, and arterial hypertension in kidney diseases in children (literature review)

Modern scientific data and the emergence of new opportunities for the development of pediatrics and nephrology are inextricably linked with medical genetics, the role of which is especially important for understanding the etiology and pathogenesis of many diseases of the urinary system. In 35–80 % of children with diffuse connective tissue diseases, kidney damage is formed, which is one of the leading causes of comorbidity of pathology and mortality of patients. Modern genetic research will allow not only to decipher the nature of diseases but also to scientifically substantiate adequate therapy. The active development of methods for the molecular diagnosis of kidney diseases opens up a large section of medicine, which can be called "molecular nephropathology". Further study of kidney diseases from the standpoint of molecular biology will allow us to take a fresh look at the pathogenesis of many diseases and solve a number of problems from the standpoint of personalized therapy, which takes into account the genetic characteristics of the patient. The active development of genetic research in nephrology has led to an understanding of the role of genetic mutations and polymorphisms leading to the occurrence of nephropathies in children. Correct clarification of the causes of the development of the disease can radically change the tactics of managing a patient by a nephrologist and rheumatologist. Determination of the genetic cause of the development of nephropathy is important in children since it justifies the need to examine other family members, it will allow predicting the risk of developing kidney pathology in diffuse connective tissue diseases, which is very important, predicting the response to immunosuppressive therapy. The development of molecular diagnostic methods is increasingly opening up prospects for a personalized approach to the study of pathology at various levels of interaction; these achievements provide a qualitative assessment of DNA, RNA, proteins, and their metabolites, which makes it possible to determine new biomarkers. The article deals with gene polymorphisms in secondary nephropathies in children with diffuse connective tissue diseases (systemic lupus erythematosus, systemic microthrombovasculitis, rheumatoid arthritis).

Perceived levels of stress, emotions and physical activity in outpatients with diffuse connective tissue diseases.

Diffuse connective tissue diseases (DCTD) are autoimmune diseases that can cause comorbidities, influencing physical and psychological aspects and increase stress. The latter may also be related to the practice of physical activity (PPA). Although evidence shows that it can contribute to patients' health, the level of PPA can decrease after the diagnosis. The aim was to evaluate the basic emotions, perceived stress (PS) and PPA levels of patients with DCTD. This is a field study with a random approach of 55 participants. We used a clinical and sociodemographic profile form for the verification of emotions, a picture with emojis of the basic emotions, the PSS-14 and the IPAQ-Brief. Data were analyzed with Mann-Whitney U and Kruskal-Wallis tests with 5% of significance. The average age was 49.1±12.9, mostly female (58.7%). High PS was reported by 54.5%; emotions such as joy (38.2%) and anxiety/fear (25.5%), as well as sadness (7.3%), were reported. About 87.3% were classified as having insufficient levels of PPA. Female patients (U=137.0; P<0.05) and insufficient PPA levels (U=86.5%; P<0.05) had higher PS scores, as well as those feeling sadness (χ2=19.0; P<0.05). The results point to the need for care with the emotional domain of these patients and suggest studies that analyze the impact of implementing PPA for this population.

Identification of immune-related diagnostic markers in primary Sjögren's syndrome based on bioinformatics analysis.

BackgroundPrimary Sjögren’s syndrome (pSS) is a relatively common diffuse connective tissue disease that often invades exocrine glands, such as the lacrimal and salivary glands, and manifests as dry eyes and dry mouth. At present, the molecular mechanism of pSS is not clear. This study was designed to explore the internal mechanism of pSS from the gene level and screen out the immune-related diagnostic markers of pSS.MethodsThe gene expression profiles GSE84844, GSE7451, and GSE40611 were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified with R software. Then, the DEGs were intersected with the immune genes obtained from the ImmPort database to acquire differentially expressed immune-related genes (DEIRGs), and functional enrichment analyses were performed. The DEIRGs were screened through the least absolute shrinkage and selection operator (LASSO) logistic regression algorithm to obtain the optimal immune-related genes (IRGs). Expression levels of the optimal IRGs were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to obtain the key genes. Next, gene chips GSE7451 and GSE40611, from other tissues, were selected as the training sets to verify the sensitivity and specificity of the diagnosis of the key genes by receiver operating characteristic (ROC) analysis.ResultsA total of 54 DEIRGs were obtained. The functional enrichment analysis results showed that they play an important role in immune and inflammatory responses. Nine optimal IRGs were screened from the DEIRGs by the LASSO logistic regression algorithm. After qRT-PCR verification, eight out of nine optimal IRGs (IL-18, JAK2, TBK1, EED, TNFSF10, TNFSF13B, CYSLTR1, and ICOS) were significantly highly expressed in pSS patients and were defined as key genes. ROC analysis identified that TNFSF13B and CYSLTR1 had high sensitivity and specificity. Finally, the lack of previous research on EED and CYSLTR1 in pSS suggests that these IRGs may be regarded as new gateways to explore the diagnosis and pathogenesis of pSS.ConclusionsThe key DEIRGs play a decisive role during the occurrence and development of pSS.

Association between sensorineural hearing loss and vitiligo: a nationwide population‐based cohort study

Vitiligo is an acquired depigmentation disease of the skin due to melanocyte destruction. A shared pathogenesis affecting melanocytes in the cochlea has been postulated. However, the association between vitiligo and sensorineural hearing loss (SNHL) is unclear. To identify the association between vitiligo and SNHL. This retrospective, nationwide cohort study included patients with vitiligo and age-, sex- and comorbidities-matched controls (propensity score matching; 1:4 ratio) from the National Health Insurance Research Database in Taiwan from 1 January 2000 to 31 December 2013. In total, 13 048 patients with vitiligo and 52 192 controls were included. SNHL developed in 0.61% patients with vitiligo and 0.29% controls. After adjusting for sex, age and comorbidities, a significant association between vitiligo and SNHL was found (adjusted hazard ratio, 2.18; 95% CI, 1.66-2.86). The other risk factors for developing SNHL included increased age, male sex, hyperlipidaemia, coronary artery disease and diffuse connective tissue diseases. In subgroup analysis, the association between vitiligo and SNHL remained significant in almost all the subgroups. A 2.2-fold increased risk of developing SNHL was found in patients with vitiligo. Proper referral to otologists for early screening and closer follow-up of SNHL should be considered for patients with vitiligo, especially for patients with older age.

Скелетно-м’язові ураження в перебігу коронавірусної хвороби (COVID-19) у педіатричній практиці. Власне спостереження: клінічний випадок

Актуальність. Пандемія коронавірусної хвороби залишається в центрі уваги вітчизняної і світової системи охорони здоров’я. Патогенні властивості вірусу SARS-CoV-2 обумовлюють ураження як нервової системи, так й інших органів і систем людини. Мета: привернути увагу лікарів до діагностики скелетно-м’язових уражень, зокрема рабдоміолізу, для запобігання можливим ускладненням при коронавірусній хворобі (COVID-19). Матеріали та методи. Нами обстежена й спостерігається група дітей зі скелетно-м’язовими ураженнями на тлі перебігу коронавірусної хвороби (COVID-19) протягом 2020–2021 років. Клінічний випадок власних спостережень такого хворого наведено в статті. Результати та висновки. В пацієнта, хлопчика 15 років, після перенесеної гострої фази коронавірусної хвороби через 33 дні з’явилися загальна слабкість, сильний біль в ділянці правого стегна і кульшового суглобу, лихоманка. Проведена диференціальна діагностика скелетно-м’язових уражень і остеомієліту. Дифузні хвороби сполучної тканини, захворювання, що відносяться до онкогематологічних, а також гепатити були виключені на підставі клінічних даних і проведених обстежень. Ідентифіковані на підставі клінічного обстеження та результатів МРТ запальні зміни клубового, затульного та грушоподібного м’язів з формуванням абсцесу, разом із високим рівнем трансаміназ крові свідчили про розвиток рабдоміолізу. Виявлений позитивний IgG до вірусу SARS-CoV-2 підтверджував зв’язок даного патологічного стану з перенесеною раніше гострою фазою COVID-19. Ознаки коагулопатії, анемія в гемограмі одночасно з клінічними симптомами рабдоміолізу, дозволили підтвердити системність ураження в перебігу коронавірусної хвороби в дитини. Своєчасна оцінка клінічної симптоматики (загальної слабкості, болю в м’язах) і рівня КФК, трансаміназ, електролітів, креатиніну, сечовини крові допоможе здійснити ранню діагностику рабдоміолізу, призначити адекватну терапію і запобігти розвитку тяжких ускладнень.

High prevalence of latent tuberculosis using the QuantiFERON-TB Gold Plus test in Takayasu arteritis.

This study aims to investigate latent tuberculosis using the QuantiFERON-TB Gold Plus method in patients with Takayasu arteritis (TA). This case-control study included 22 patients with TA (3 males, 19 females; median age: 36.5 years; IQR, 32 to 50 years), 22 healthy individuals (3 males, 19 females; median age: 38.5 years; IQR, 32.5 to 50 years), and 66 patients with diffuse connective tissue diseases (DCTDs) (4 males, 62 females; median age: 41 years; IQR, 29.8 to 54 years). Two control groups were formed: (i) age- and sex-matched healthy individuals and (ii) patients with other DCTDs. Epidemiological data were collected, and the QFT-Plus test was performed. The QFT-plus positivity was compared among the groups. A higher prevalence of QFT-Plus positive cases was observed in the TA group (8/22) than in the healthy control group (1/22) (p=0.020) or in the group with other DCTDs (3/66) (p=0.001). There was a statistically significant difference in the past pulmonary tuberculosis prevalence between the TA and DCTD groups (p=0.013). The prevalence of latent tuberculosis in TA patients (36.4%) was higher than that in both control groups and higher than the prevalence of latent tuberculosis among the general Brazilian population. Although a positive association was found, it is not possible to establish a direct cause-effect relationship. Given the increasing use of anti-cytokine therapies in TA, it is necessary to thoroughly screen patients with TA before initiating immunosuppressive therapy to avoid tuberculosis reactivation.

Substantiation of the composition of a rectal dosage form containing ketoprofen and glucosamine sulfate for the treatment of rheumatoid arthritis

In the course of this study, it was found that currently more than 30 million people are forced to take non-steroidal anti-inflammatory drugs (NSAIDs) daily. It is reliably known that nonsteroidal anti-inflammatory drugs with prolonged use cause a number of side effects, the main of which are erosive and ulcerative changes in the mucous membrane of the gastrointestinal tract. Special attention is paid to the classification and comparative evaluation of various NSAIDs and possible complications in the case of their use. As a result of the performed analysis, it was found that rectal forms have been developed for most NSAIDs, which is convenient for use in pediatric practice, in patients with gastropathies, nausea, vomiting, swallowing disorders, in an unconscious state. The common sides of their pharmacological action are anti-inflammatory, antipyretic, analgesic effects due to inhibition of cyclooxygenase I, II activity and leading to disruption of arachidonic acid metabolism with suppression of prostaglandin synthesis in the focus of inflammation. Data analysis showed that NSAID suppositories are prescribed for: articular syndrome; pain in the spine, neuralgia, myalgia, traumatic inflammation of soft tissues and musculoskeletal system; rheumatism, diffuse connective tissue diseases; dysmenorrhea.

Advances in therapeutic targets-related study on systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic and autoimmunity-mediated diffuse connective tissue disease. The mainstay of treatments for SLE mainly relies on corticosteroids and immunosuppressants, which have a series of unavoidable side effects. Therefore, it is of fundamental importance to search novel therapeutic targets for better treatment with favorable efficacy and minor side effects. Recent studies shed light on potential therapeutic targets for SLE, mainly covering the followings: B-cell/plasmocyte-related targets [B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), CD20, CD22, CD19/FcγRIIb, Bruton tyrosine kinase (Btk), and proteasome], T cell-related targets [calcineurin, mammalian target of rapamycin (mTOR), regulatory factor X1 (RFX1), and Rho kinase], macrophage-related targets (macrophage migration inhibitory factor), intracellular signaling molecules, cytokines (cereblon, histone deacetylase 6, Janus activated kinase/signal transducer and activator of transcription), co-stimulating factors (CD28/B7, CD40/CD154), IgE autoantibody, and gut microbiome. Among them, belimumab (a humanized monoclonal antibody against B-lymphocyte stimulator) and telitacicept (a recombinant human B-lymphocyte stimulator receptor-antibody fusion protein) have been sequentially approved for the clinical treatment of SLE in China. A variety of new targeted-therapy drugs are in the Phase 2 or Phase 3 clinical trials,among which anifrolumab (a human monoclonal antibody against type I interferon receptor subunit 1) has completed a Phase 3 clinical trial with good responses achieved, although its incidence of herpes zoster is higher than that in the control group. The research progress in both molecular mechanisms and new drug development for different therapeutic targets have greatly promoted our better and in-depth understanding of the pathogenesis of SLE, and have also reflected the complexity and heterogeneity of the disease. Successful development and clinical application of more novel therapies would no doubt usher in a new era of individualized treatment for SLE in the future.

Correlation Analysis between Gut Microbiota and Metabolites in Children with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune-mediated diffuse connective tissue disease characterized by immune inflammation with an unclear aetiology and pathogenesis. This work profiled the intestinal flora and faecal metabolome of patients with SLE using 16S RNA sequencing and gas chromatography-mass spectrometry (GC-MS). We identified unchanged alpha diversity and partially altered beta diversity of the intestinal flora. Another important finding was the increase in Proteobacteria and Enterobacteriales and the decrease in Ruminococcaceae among SLE patients. For metabolites, amino acids and short-chain fatty acids were enriched when long-chain fatty acids were downregulated in SLE faecal samples. KEGG analysis showed the significance of the protein digestion and absorption pathway, and association analysis revealed the key role of 3-phenylpropanoic acid and Sphingomonas. Sphingomonas were reported to be less abundant in healthy periodontal sites of SLE patients than in those of HCs, indicating transmission of oral species to the gut. This study contributes to the understanding of the pathogenesis of SLE disease from the perspective of intestinal microorganisms, explains the pathogenesis of SLE, and serves as a basis for exploring potential treatments for the disease.

Increased Incidence of Autoimmune and Infectious Diseases Among a Large Group of Diffuse Large B-Cell Lymphoma (DLBCL) Survivors: A Population-Based Study

▪Introduction: Treatments for lymphoma have improved significantly over the last three decades, particularly since the advent of rituximab for non-Hodgkin lymphoma. Improved survival rates have led to an increasing number of lymphoma survivors. Many of the treatments for lymphoma as well as lymphoma itself are known to affect the immune system; yet, despite the range of immune perturbations lymphoma survivors may have experienced, very little is known about their mid- and long-term immune health. Therefore, we investigated whether survivors of diffuse large B-cell lymphoma (DLBCL) have altered risk of developing autoimmune and infectious diseases compared to other cancer survivors.Methods: All 21,690 Californians aged ≥18 years when newly diagnosed with DLBCL during 1991-2012, surviving a minimum of 1 year from diagnosis and without evidence of HIV/AIDS were identified in the California Cancer Registry and followed in California hospital, emergency department and ambulatory surgery discharge databases through 2014. We categorized discharge diagnoses to classify autoimmune and infectious diseases. To avoid possible relationships to DLBCL pathogenesis, we excluded conditions identified prior to or within 1 year of cancer diagnosis from our incidence analyses. We calculated incidence rate ratios (IRRs) and associated p-values comparing the incidence of autoimmune and infectious diseases among female and male DLBCL survivors to that among breast and prostate cancer survivors >1-10 years after cancer diagnosis using multivariable Poisson regression models adjusting for age, race/ethnicity and year of cancer diagnosis. We estimated the cumulative incidence of developing new autoimmune and infectious disease conditions >1-10 years after diagnosis, accounting for death as a competing risk.Results: Most DLBCL patients had at least one hospitalization prior to or within 1 year of diagnosis (67.9%) and >1-10 years of diagnosis (78.6%). Median follow-up time was somewhat longer for female breast (8.2 years) and male prostate (8.3 years) cancer survivors than for DLBCL survivors (female, 6.3 years; male, 5.9 years). In DLBCL survivors, we identified a higher cumulative incidence of any autoimmune or any infectious disease diagnosis than in breast or prostate cancer survivors (Figure 1). After adjustment for age, race/ethnicity and year of diagnosis, we found DLBCL survivors to have a more than two-fold higher incidence of fungal pneumonia (IRR 6.2 versus breast; IRR 8.2 versus prostate), viral pneumonia (IRR 3.4 versus breast; IRR 4.5 versus prostate), bacteremia (IRR 2.6 versus breast; IRR 3.1 versus prostate), and CNS infections (IRR 2.6 versus breast; IRR 3.2 versus prostate) (all p<0.0001). Compared to prostate cancer survivors, male DLBCL survivors had higher incidence of liver abscesses (IRR 3.0), empyema (IRR 2.4), bacterial pneumonias (IRR 2.1), and infections of implanted devices (IRR 2.1). For autoimmune diagnoses, we found DLBCL survivors to have a higher incidence of autoimmune hemolytic anemia (IRR 10.1 versus breast; IRR 8.7 versus prostate), immune thrombocytopenia (IRR 3.1 versus breast; IRR 4.7 versus prostate), and diffuse connective tissue diseases (IRR 2.1 versus breast; IRR 2.5 versus prostate) (all p<0.0001). In comparing male DLBCL survivors to prostate cancer survivors, we additionally found an increase in acquired coagulation factor deficiencies (IRR 2.1), caused by autoimmunity against clotting factors. Finally, we found that DLBCL survivors had a markedly increased incidence of being diagnosed with impaired humoral immunity (IRR 16.0 versus breast; IRR 14.0 versus prostate), perhaps a reflection of persistent hypogammaglobulinemia.Conclusion: These findings in a large, population-based study suggest that compared to survivors of other common cancers, DLBCL survivors experience excess immune-related conditions, some expected (such as autoimmune hemolytic anemia and thrombocytopenia) and others unexpected (such as fungal and viral pneumonias and diffuse connective tissue diseases). This information suggests possible lasting effects of lymphoma and its treatments on the immune system and motivates further examination of immune function in DLBCL survivors. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Research Progress on the Relationship between Polymorphism and SLE of Vitamin D Metabolic Pathway Related Gene

Vitamin D is a class of hormones necessary to maintain normalphysiological activities of the body. A large number of studies have shownthat vitamin D, as a fat-soluble vitamin, is not only related to calcium andphosphorus metabolism, but also closely related to immune regulation,humoral regulation, cell cycle and so on. Systemic Lupus erythema-Tosus(SLE) is a specific autoimmune diffuse connective tissue disease thatcauses tissue and organ damage under the joint action of multiple factorssuch as environment and heredity. Among many factors, the vitamin Dmetabolism pathway gene is particularly important for its influence. Someliterature has shown that the genetic polymorphism of vitamin D metabolicpathway genes is correlated with SLE. Therefore, by referring to relevantliterature, this paper summarized the progress in the research on themechanism of genetic polymorphism of vitamin metabolism pathway genesand the development of SLE.

Leisure Activities for Patients with Diffuse Connective Tissue Diseases

Leisure is everyone right, regardless of the clinical condition of each individual. The quality of life (QoL) of patients with dermatoses has been related to the practice of leisure activities (PLA); however, little is known about this practice in these patients. This study aimed to verify the PLA in patients with Diffuse Connective Tissue Diseases (DCTD). This is a descriptive, qualitative, and quantitative field study with patients seen at the Dermatology Outpatient Clinic (Hospital de Clínicas) of the University of Campinas (UNICAMP), São Paulo, Brazil. A form was used, containing closed questions about the sociodemographic and clinical profiles, and an open question about leisure. The responses were categorized according to the classification of leisure cultural content. Descriptive statistics, construction of a crosstable and the Mann-Whitney and Kruskal-Wallis tests were used. Data from 62 patients were collected, who aged between 19.4 and 75.3 years (average of 49.32±12.55 years). Among the patients, 80.6% were female and 70.9% were diagnosed with Cutaneous or Systemic Lupus Erythematosus (LE). The most practiced leisure activities were those related to manual and virtual content, mentioned by 24.6% of the patients. Another 18.0% reported preferring to stay at home or sleep (other activities), and no patient reported physical-sports or tourist leisure practices. The PLAs were little varied, showing 75.8% of the patients taking only one type of content related to these practices and 12.9% not carrying out any leisure activities. The elderly were the ones who most reported manual and virtual activities. An association was found between the variety of leisure content practiced and literacy level. Illiterate patients were those who least reported activities related to leisure, when compared to those who completed elementary school (X² = 24.686; p= 0.035). Before diagnosis, 56.5% of the patients performed physical activities, of which 27.4% could be classified as physical-sports leisure. After the disease development, only 19.7% of them maintained physical activities, and, of all the activities practiced by them, only 9.7% could be considered as leisure activities, but none as physical-sports leisure. Thus, it appears that leisure practices among patients with DCTD are scarce and little varied, which interferes with their QoL. The orientation and practice of these activities are necessary so that they can make choices and vary the types of activities practiced. Likewise, more studies, which can support actions that encourage and enable the leisure practices of these patients, play an important role.

Clinical observation of extremely elevated erythrocyte sedimentation rate

To analyze the clinical features of adult patients with extremely elevated erythrocyte sedimentation rate (ESR, ESR ≥ 100 mm/1 h), so as improve the ability of clinicians to use erythrocyte sedimentation rate to assist in the diagnosis and treatment of diseases. A retrospective cohort study was conducted to examine the clinical data of patients with ESR ≥ 100 mm/1 h admitted to the First Affiliated Hospital of Kunming Medical University from January 1st 2019 to December 31st 2019. The age, gender, clinical diagnosis, first ESR level after admission, blood routine, liver function, renal function, coagulation function and C-reactive protein (CRP) within 24 hours after admission were collected. Patient cohorts were divided into youth group (18-65 years old), middle-aged group (66-79 years old) and elderly group (≥ 80 years old) according to the new standards of human age classification of World Health Organization (WHO) 2019. Patient cohorts were also divided into infectious disease group, hematological disease group, autoimmune disease group, renal failure group and others according to their respective clinical diagnosis. The distribution of extremely elevated ESR in each group, and the correlation between ESR and various laboratory indicators were analyzed. (1) Among 429 patients with ESR ≥ 100 mm/1 h, there were 236 males and 193 females. There was no significant difference in ESR levels between males and females [mm/1 h: 108.00 (103.00, 119.75) vs. 117.00 (105.50, 140.00), P = 0.234]. (2) The age of 429 patients ranged from 18 to 98 years old, the average age was (53.70±18.70) years old. There were 310 cases in the youth group, 87 cases in the middle-aged group and 32 cases in the elderly group. The ESR level of the young group was significantly lower than that of the middle-aged group and the elderly group [mm/1 h: 108.00 (103.00, 120.00) vs. 119.00 (107.00, 140.00), 120.00 (110.25, 140.00), both P < 0.01]. (3) The main diagnoses associated with extremely elevated ESR were infectious diseases [157 cases (36.6%)], hematological system diseases [127 cases (29.6%)], autoimmune diseases [74 cases (17.2%)]. Pulmonary infection accounted for 58.0% (91/157) of infectious diseases. Hematopoietic stem cell diseases accounted for 45.7% (58/127), lymphocyte and plasma cell diseases accounted for [37.0% (47/127)] and erythrocyte diseases accounted for [11.0% (14/127)] of the hematological system diseases. Diffuse connective tissue diseases accounted for 75.7% (56/74) of autoimmune diseases. (4) Spearman correlation analysis showed that the extremely elevated ESR in all patients was significantly negatively correlated with the levels of red blood cell count (RBC), hemoglobin (HB) and hematocrit (HCT) (ρ value was -0.395, -0.381 and -0.383, respectively, all P < 0.01), the ESR was significantly positively correlated with the level of fibrinogen (FIB; ρ = 0.345, P < 0.01). A total of 266 patients were tested for both ESR and CRP, and there was no significantly correlation between ESR and CRP level (ρ = -0.019, P = 0.756). The extremely elevated ESR was more common in pulmonary infections diseases, hematopoietic stem cell diseases, lymphocyte and plasma cell diseases, erythrocyte diseases and diffuse connective tissue diseases. The extremely elevated ESR was significantly correlated with the levels of RBC, HB, HCT and FIB.