Elevated serum IL-6 levels predict treatment interruption in patients with moderate to severe psoriasis: a 6-year real-world cohort study

Abstract Background: Real-world, primary data on the treatment of psoriasis are scarce, especially concerning the role of soluble biomarkers as outcome predictors. Objective: The authors evaluated the utility of Th1/Th17 serum cytokines along with clinical characteristics as predictors of drug survival in the treatment of psoriasis. Methods: The authors consecutively included participants with moderate to severe psoriasis who were followed up for 6 years. Baseline interferon-α, tumor necrosis factor-α, and inter-leukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A were measured using a cytometric bead array; clinical data were assessed. The authors calculated hazard ratios (HRs) for drug survival using a Cox proportional hazards model. Results: The authors included 262 patients, most of whom used systemic immunosuppressants or biologics. In the multivariate model, poor quality of life measured by the Dermatology Life Quality Index (HR = 1.04; 95% CI 1.01-1.07; p = 0.012) and elevated baseline IL-6 (HR = 1.99; 95% CI 1.29-3.08; p = 0.002) were associated with treatment interruption. Study limitations: The main limitation of any cohort study is the presence of confounders that could not be detected in clinical evaluation. Conclusions: Poor quality of life and elevated baseline serum IL-6 level predicted treatment interruption in patients with moderate to severe psoriasis. Although IL-6 is not the most important mediator of the inflammatory pathway in the skin environment, it is an interesting biomarker candidate for predicting psoriasis treatment response.

Clinical significance of nucleolar antinuclear antibodies associated with the nucleolar immunofluorescence pattern in autoimmune disease / 国际检验医学杂志

Objective To explore the clinical significance of nucleolar antinuclear antibodies(ANA)in re-lated diseases.Methods This study was a retrospective study.Clinical samples of 71780 patients who visited the hospital from January 2017 to May 2022 were collected.Indirect immunofluorescence was used to detect ANA in clinical samples.Statistical analysis was conducted on the positivity rate of nucleolar ANA in clinical patients,as well as the relevant clinical information and laboratory characteristics of patients with autoimmune diseases(AID)with nucleolar ANA positivity.Results Among 71780 patients who underwent routine ANA testing,16778 were positive for ANA,with a positive rate of 23.37％.Among them,there were 1 708 cases of nucleolar type,accounting for 2.38％of all routine ANA tests,and the proportion of ANA positive cases was 10.18％.There was a statistically significant difference in the positive rate of nucleolar ANA between patients of different genders in the＞20-＜50 year old group and the ≥ 50 year old group(P＜0.05),while there was no statistically significant difference in the positive rate of nucleolar ANA between patients of different genders in the ≤ 20 year old group(P＞0.05).There was a statistically significant difference in the positivity rate of nucleolar ANA among women of different age groups(P＜0.05),among them,the highest positive rate of nucleolar ANA was found in women aged between 20 and 50 years old.There was no statistically significant difference in the positive rate of nucleolar ANA among males of different age groups(P＞0.05).The positivi-ty rate of ANA was the highest among patients in the Department of Rheumatology and Immunology(70.35％),but nucleolar ANA positivity was mainly seen in departments such as Reproductive Medicine Cen-ter(12.90％),Respiratory Medicine(12.40％),and Neurology(11.29％),and the difference in positivity rates between departments was statistically significant(P＜0.05).Out of 1 708 nucleolar ANA positive indi-viduals,420 underwent ANA titers,including 34 AID patients and 386 non AID patients.There was no statis-tically significant difference in nucleolus positive titers between non AID patients and AID patients(P＞0.05).Conclusion The nucleolus type is a common fluorescence pattern in ANA positive individuals,and there are gender and age differences in ANA positive individuals.The positive rate and titer of nucleolar ANA vary among different AID diseases.Combined with other immune function indicators,and it is helpful for early differential diagnosis of AID.

Establishment and evaluation of nomogram for differential diagnosis of systemic lupus erythematosus based on laboratory indications / 上海交通大学学报（医学版）

Objective·To establish a nomogram for the differential diagnosis of early systemic lupus erythematosus(SLE)and other autoimmune diseases based on laboratory indications,and to evaluate its efficacy.Methods·A total of 535 SLE patients admitted to the First Hospital of Lanzhou University from January 2017 to December 2021 were selected as SLE group,and 535 patients with other autoimmune diseases during the same period were selected as control group.Basic information and laboratory test indicators of the SLE group and control group were collected and compared.The SLE group and control group were randomly assigned to the training set and the validation set at a ratio of 7∶3,respectively.LASSO regression method and multivariate Logistic regression were used to select the main risk factors of SLE.The nomogram for differential diagnosis of early SLE(SLE nomogram)was established according to the selected main risk factors.Bootstrap method was used to conduct internal repeated sampling for 1 000 times to calibrate the nomogram.The receiver operator characteristic curve(ROC curve)and decision curve analysis(DCA)were performed to evaluate the differential diagnosis ability and the value in clinical application of SLE nomogram,respectively.The"DynNom"package of R language was used to convert the nomogram into an electronic calculator,and its consistency with SLE nomogram was verified by data from 3 groups of patients.Results·LASSO regression and multivariate Logistic regression identified six major risk factors for SLE,including antinuclear antibody(ANA),anti-double-stranded DNA(anti-dsDNA)antibody,anti-ribonucleoprotein antibody/anti-Simth antibody(anti-nRNP/Sm),anti-ribosomal P protein(anti-P)antibody,anti-nucleosome antibody(ANuA)and urinary protein(PRO),which were used to construct the SLE nomogram.The calibration curve of the SLE nomogram had standard errors of 0.009 and 0.015 in the training set and validation set,respectively,and its area under the curve(AUC)was 0.889 and 0.869,respectively.The results of DCA showed that when the risk threshold of SLE nomogram was 0.15?0.95,the model achieved more net benefit.The prediction results of the electronic calculator showed that when ANA(titer 1∶100)was positive in SLE patient No.1,the prevalence was 0.166;when both ANA(titer 1∶100)and ANuA(titer 1∶100)were positive in patient No.2,the prevalence was 0.676;when all of PRO,ANA(titer 1∶100),ANuA(titer 1∶100)and anti-P antibody(titer 1∶100)were positive in patient No.3,the prevalence was 0.990,which was consistent with the differential diagnosis results of the SLE nomogram.Conclusion·The established SLE nomogram based on ANA,anti-dsDNA antibody,anti-nRNP/Sm,anti-P antibody,ANuA and PRO and its conversion into an electronic calculator can effectively distinguish early SLE from other autoimmune diseases,and have important clinical application value.

Regulation and mechanism of lncRNA H19 in autoimmune diseases / 中国免疫学杂志

Long non-coding RNA(lncRNA)is a type of non-protein-coding RNA with a length of at least 200 nucleotides.Ex-isting evidence shows that lncRNA affects the growth and development of humans and the occurrence of diseases through various mech-anisms,and plays an irreplaceable role in the differentiation and activation of immune cells and the development process of autoim-mune diseases.In recent years,lncRNA H19 has been found to play a unique regulatory function in pathological processes related to autoimmune diseases,such as inflammation and fibrosis.Therefore,the molecular mechanism involved in H19 is expected to become a potential target for the treatment of autoimmune diseases.In this review,we discussed the related mechanisms of H19 involved in the pathogenesis of autoimmune diseases based on the known functions of H19 and summarized the research results of H19 in several com-mon autoimmune diseases.

Research progress in roles of fibroblast activation in tissue fibrosis,autoimmune diseases and tumor disease / 中国药理学与毒理学杂志

Fibroblasts are stromal cells widely distributed in tissues and organs throughout the body.Fibroblasts are involved in the synthesis and remodelling of the extracellular matrix.Fibroblasts participate in physiopathological processes such as tissue damage repair,inflammatory responses and immune regulation.Large numbers of activated fibroblasts have been found in fibrosis,autoimmune diseases and tumor lesions.Activated fibroblasts participate in tissue fibrosis and influence the tumor microenvi-ronment mainly by secreting collagen and fibronectin.They also secrete a variety of inflammatory and growth factors that play an immunomodulatory role in autoimmunity and tumors.In recent years,it has been found that modulating fibroblast activation can effectively delay the development of these diseases,and that targeting fibroblast activation biomarkers can assess the development and treatment of these diseases.Therefore,the use of fibroblast-targeted drugs and therapeutic tools is expected to achieve new breakthroughs in the clinical management of fibrosis,autoimmune diseases and tumors.

Pertussis toxin in involves the development of interstitial lung disease in an experimental autoimmune myositis mice modelby inducing the formation of neutrophil extracellular traps / 中华风湿病学杂志

Objective:To test the hypothesis that Pertussis toxin (PTX) can promote the occurrence of interstitial lung disease (ILD) in experimental autoimmune myositis (EAM) model and clarify the potential pathogenic mechanism.Methods:EAM mice model were induced by Skeletal muscle thomogenate with or without PTX, and the relationship between ILD phenotypes and neutrophil extracellular traps (NETs) infiltration was analyzed by histopathological and serological studies in EAM with PTX group and EAM without PTX group. Healthy mice were given PTX alone intraperitoneally to clarify whether NETs formation could be induced in vivo, and neutrophils separated from healthy human blood were intervened with PTX to induce NETs formation in vitro. The data was tested for normality using Shapiro-Wilk. Statistical methods and were analyzed using t-test or ANOVA, and multiple comparisons between different groups were tested using Tukey test. Results:Compared with EAM without PTX group, lung tissues in EAM with PTX group had multiple pathological changes similar to polymyositis/dermatomyositis-related ILD. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the main pathological types. The pulmonary interstitial lesions were accompanied by significant infiltration of NETs; and serum NETs markers levels were obviously elevated in EAM with PTX group, compared with the control group [ n=5, (87±10) ng/ml], cfDNA levels were statistically significantly elevated in both the EAM without PTX group [ n=4, (115±27) ng/ml] and the EAM with PTX group [ n=7, (150±50) ng/ml] ( F=4.24, P=0.038); Cit-H3-DNA levels were elevated in the EAM without PTX group ( n=4, 0.24±0.09), and in the EAM EAM with PTX group ( n=6, 0.33±0.11) compared with the control group ( n=4, 0.13±0.02) ( F=6.21, P=0.016). After PTX intervention, serum cfDNA levels were higher in the PTX group [ n=3, (100±40) ng/ml] than in the control group [ n=3, (45±12) ng/ml, t=2.27, P=0.086]; PTX also induced neutrophils to form NETs in vitro. Conclusion:PTX may promote the development of ILD in EAM mice model by inducing the formation of NETs, indicating that EAM mice can serve as a model for targeting NETs to study the pathogenesis ILD.

Cases analysis and etiology discussion of thymoma with alopecia areata / 中华胸心血管外科杂志

Objective:Analyzed the clinicopathological features of thymoma with alopecia areata, and discussed the pathogenesis and treatment methods.Methods:The clinicopathologic data of patients with thymoma who underwent surgery from August 1, 2015 to July 31, 2020 in Beijing Tongren Hospital, Capital Medical University were reviewed. Transversally analyzed the patients of thymoma with alopecia areata and longitudinally compared with the patients of thymoma without alopecia areata after 1﹕10 matched by propensity score matching.Results:A total of 252 patients of thymoma were enrolled, including 6 patients with alopecia areata, accounting for 2.38%. The anti-AchR antibody, CD4 + /CD8 + T inversion in serum and myasthenia gravis were present in the all 6 thymoma patients with alopecia areata, which were significantly higher than those in the group of thymoma without alopecia areata. Besides myasthenia gravis, the proportion of complicated with other autoimmune diseases in thymoma patients with alopecia areata was significantly higher than that of thymoma patients without alopecia areata[83.33%(5/6) vs. 20.00%(12/60), P=0.003]. After operation, 5 patients’ alopecia areata were improved in 6 thymoma patients with alopecia areata(83.33%, 5/6). Conclusion:The thymoma patients with alopecia areata always complicated with myasthenia gravis and other autoimmune diseases. The pathogenesis may be associated with autoimmune CD8 + T lymphocytes produced by thymoma. At present, surgery is still the most effective way to improve thymoma-associated alopecia areata.

Application and research progress of cell-free DNA in the diagnosis and treatment of related disease / 中华检验医学杂志

Cell-free DNA (cfDNA) is the DNA fragment existing in human extracellular fluid. In specific physiological process (such as pregnancy) or pathological conditions (such as human malignancies), the contents of cfDNA in extracellular fluid will abnormally change. The contents and molecular characteristics of cfDNA make it have the potential as a kind of biomarker for diseases′ diagnosis. With the development of cfDNA detection technology such as sequencing and mass spectrometry, liquid biopsy based on cfDNA detection has been widely used in clinical tumor diagnosis, tumor treatment, prenatal examination, and research in autoimmune diseases. A systematic summary of the latest research progress in the development of cfDNA detection technology and the clinical application of liquid biopsy, as well as the research progress of cfDNA in the diagnosis and treatment of related diseases is summarized in this review.

Mendelian randomization study on body mass index and 25 types of autoimmune diseases / 预防医学

Objective@#To examine the causal relationship between body mass index (BMI) and 25 types of autoimmune diseases (ADs) using Mendelian randomization (MR) study method.@*Methods@#The genome-wide association study (GWAS) data for BMI and 25 types of ADs were obtained from IEU OPEN GWAS database. Single nucleotide polymorphisms (SNPs) related to BMI were used as instrumental variables, 25 types of ADs were used as study outcomes, and MR analysis was performed using inverse variance weighted (IVW) method. Heterogeneity was evaluated using Cochran's Q test, horizontal pleiotropy was tested using MR-Egger regression and MR-PRESSO, and results robustness was verified with leave-one-out method.@*Results@#Cochran's Q test showed heterogeneity of MR analysis results (P<0.05), and a random effect model was employed. The results of MR analysis showed that elevated BMI increased the incidence risks of type 1 diabetes mellitus (OR=1.519, 95%CI: 1.281-1.801), IgA nephropathy (OR=1.227, 95%CI: 1.134-1.327), adult Still disease (OR=1.002, 95%CI: 1.001-1.003), multiple sclerosis (OR=1.303, 95%CI: 1.115-1.523), narcolepsy (OR=1.029, 95%CI: 1.017-1.040), Hashimoto thyroiditis (OR=1.561, 95%CI: 1.391-1.751), autoimmune hepatitis (OR=1.481, 95%CI: 1.076-2.038), rheumatoid arthritis (OR=1.209, 95%CI: 1.054-1.386), psoriasis vulgaris (OR=1.719, 95%CI: 1.427-2.070) and pernicious anemia (OR=1.001, 95%CI: 1.000-1.002). No causal relationship was found with other ADs (all P>0.05). MR-Egger regression identified no horizontal pleiotropy of instrumental variables (all P>0.05), while MR-PRESSO test identified partial horizontal pleiotropy (all P<0.05), which remained consistent with the original results after adjustment (P>0.05). Leave-one-out analysis showed results robustness.@*Conclusion@#There are causal relationship among BMI and type 1 diabetes mellitus, IgA nephropathy, adult Still disease, multiple sclerosis, narcolepsy, Hashimoto thyroiditis, autoimmune hepatitis, rheumatoid arthritis, psoriasis vulgaris and pernicious anemia.

vitíligo, estrés psicológico y bioquímica del cerebro: Una revisión sistemática desde la neurociencia

Objetivo: El propósito de este estudio es establecer los mecanismos de la actividad Bioquímica a través del Estrés Psicológico que influyen en la enfermedad del vitiligo desde una perspectiva neurocientifica, mediante una revisión sistemática de la literatura de los últimos 5 años. Método: La búsqueda sistemática se llevó a cabo en las bases de datos Scopus, PubMed y Web of Science para identificar los estudios que describan la enfermedad de Vitiligo, el estrés psicológico y la bioquímica del cerebro, se establecieron criterios de inclusión y exclusión para la selección de los artículos, así mismo, se evaluó su calidad y pertinencia. Resultados: La revisión sistemática arrojó 15.503 artículos, 70 fueron preseleccionados de acuerdo a lo informado en el resumen y validados para lectura completa. Para la síntesis narrativa se utilizaron 23 artículos científicos. Conclusión: La enfermedad de vitiligo guarda una estrecha relación con el estrés psicológico y está acompañado de un desequilibrio bioquímico que conduce a un proceso inflamatorio y destructivo de los melanocitos de la piel.

Objective: The purpose of this study is to establish the mechanisms of biochemical activity through psychological stress that influence vitiligo disease from a neuroscientific perspective, through a systematic review of the literature of the last 5 years. Method: Systematic search was carried out in the Scopus, PubMed and Web of Science databases to identify studies describing Vitiligo disease, psychological stress and brain biochemistry, inclusion and exclusion criteria were established for the selection of articles, their quality and relevance were evaluated. Results: The systematic review yielded 15,503 articles, of which 70 were pre-selected as reported in the summary and validated for full reading. For the narrative synthesis 23 scientific articles were used. Conclusion: Vitiligo disease is closely related to psychological stress and is accompanied by a biochemical imbalance that leads to an inflammatory and destructive process of skin melanocytes.

Actividad y discapacidad en pacientes cubanos con artritis reumatoide como factores que influyen en la sexualidad / Activity and Disability in Cuban Patients with Rheumatoid Arthritis as Factors that Influence Sexuality

Introducción: La artritis reumatoide es una enfermedad autoinmune de carácter inflamatorio y crónico. La afectación en la esfera sexual es frecuente, compromete a ambos sexos y se relaciona con factores como el dolor, la discapacidad y el consumo de medicamentos. Esta afectación no ha sido suficientemente abordada en la literatura a pesar de su prevalencia, y en Cuba no se han reportado hasta el momento estudios relacionados sobre este tema de investigación. Objetivo: Determinar el impacto de la artritis reumatoide en la sexualidad y su relación en la actividad y la discapacidad. Métodos: Se realizó un estudio monocéntrico, transversal, descriptivo. Se incluyeron los pacientes con un diagnóstico de artritis reumatoide en el período comprendido de septiembre de 2019 a junio de 2021. Se utilizó el cuestionario Qualisex para evaluar el impacto de la artritis reumatoide en la sexualidad. Resultados: En el estudio doscientos veintiséis pacientes fueron incluidos, la media de edad fue de 53,38 años (DE ± 12,22) el 82,7 por ciento fueron mujeres. Al responder el autocuestionario Qualisex el 73,9 por ciento de los sujetos presentaron afectación en la sexualidad. No se estableció una relación significativa entre la afectación en la esfera sexual y el tiempo de evolución. A diferencia de los niveles altos de actividad y discapacidad. Conclusiones: En la población estudiada se presentó afectación en la sexualidad, no obstante, esta no se relacionó con el tiempo de evolución de la artritis reumatoide. Se encontró asociación entre la actividad de la enfermedad y la capacidad funcional con la afectación en la esfera sexual(AU)

Introduction: Rheumatoid arthritis is a chronic, inflammatory autoimmune disease. Disorders in the sexual sphere is frequent, it affects both sexes and it is related to factors such as pain, disability and medication consumption. This condition has not been sufficiently addressed in the literature despite its prevalence and in Cuba no studies related to the topic under study have been reported to date. Objective: To determine the impact of rheumatoid arthritis on sexuality and its relationship with activity and disability. Methods: A monocentric, cross-sectional and descriptive study was carried out on patients with a diagnosis of rheumatoid arthritis, from September 2019 to June 2021. The Qualisex questionnaire was used to evaluate the impact of rheumatoid arthritis on sexuality. Results: Two hundred twenty-six patients were included, the mean age was 53.38 years (SD ± 12.22) and 82.7percent were women. When answering the Qualisex self-questionnaire, 73.9percent of the subjects had effects in their sexuality. No significant relationship was established between the involvement in the sexual sphere and the time of evolution. Conclusions: The impact on sexuality in the studied population was not related to the duration of rheumatoid arthritis. On the other hand, an association was found between disease activity and functional capacity with effects in the sexual sphere(AU)

Pénfigo foliáceo, variedad seborreica, reporte de caso / Pemphigus foliaceus, seborrheic variety, case report

Presentación del caso. Se expone el caso de un paciente masculino de 48 años de edad, sin antecedentes médicos conocidos, que presentó múltiples lesiones en forma de placas eritematocostrosas fácilmente descamativas, inicialmente en tórax anterior, que se esparcían sobre el rostro y cuero cabelludo sin afectar las mucosas. Intervención terapéutica. El manejo hospitalario se basó fundamentalmente en el uso de esteroides tópicos y sistémicos, así como el manejo de las infecciones sobreagregadas a las lesiones dermatológicas y el apoyo psicológico del paciente. Se tomó biopsia de piel donde se evidenció la presencia de acantólisis, confirmando el diagnóstico de esta enfermedad autoinmunitaria. Evolución clínica. Luego del tratamiento se logró una reducción de las múltiples lesiones descamativas, el control de la infección local y la recuperación de la piel del paciente, la cual a pesar de aún presentar cicatrices se encontraba con sus funciones restituidas

Case presentation. a 48-year-old male with no known medical history who presented multiple lesions in the form of easily desquamative erythematous and crusted plaques, initially on the anterior thorax, which spread over the face and scalp without affecting the mucous membranes. Treatment. In-hospital management was mainly based on topical and systemic steroids, the management of infections superadded to the dermatologic lesions, and psychological support for the patient. A skin biopsy was taken where acantholysis was evidenced, confirming the autoimmune disease diagnosis. Outcome.After treatment, the multiple scaly lesions were reduced, the local infection was controlled, and the patient's skin recovered although it still had scars, its functions were restored

Evaluación del panel de enfermedades hepáticas autoinmunes (INMUNOBLOT) en el diagnóstico de enfermedades hepáticas / Utility of the detection of autoantibodies in autoinmune liver diseases using immunoblot

INTRODUCTION: For the diagnosis of liver diseases, clinical criteria, biochemical, immunological and histological parameters are included. The autoimmune panel is an immunoblot that contemplates the detection of antibodies against 9 different hepatic antigens, which could guide the diagnosis of these pathologies. OBJECTIVE: To describe the usefulness of the autoimmune panel in the diagnosis of liver diseases. Methods: Observational, descriptive study. All autoimmune panels performed between January 2020 and August 2021 (n = 279) were reviewed, and the ones with positive result selected (n = 101). Clinical records were reviewed, including: clinical, biochemical, immunological and histological characteristics. Diagnosis was determined by clinical suspicion (clinical, biochemical and immunological parameters), only through autoimmune panel, and according to liver biopsy in available cases. RESULTS: 45 patients with complete clinical history were included in the analysis; 82% women, median age 58 years (16-79). Clinical suspicions included autoimmune hepatitis (AIH) in 12 patients (27%), primary biliary cholangitis (PBC) in 10 patients (22%), overlap syndrome (AIH/PBC) in 17 (38%), and others in 6 (13%). The diagnosis of PBC was confirmed by autoimmune panel in 9/10 and 11/17 patients with clinical suspicion of PBC and HAI/PBC, respectively. Of the 27 patients with initial clinical suspicion of PBC, 14 had negative AMA and AMA-M2 (6 had Sp100 and 5 gp210 as the only markers and 3 had positive Sp100 and PML). In 10/14 patients, the diagnosis was confirmed by panel and/or compatible liver biopsy. CONCLUSION: The autoimmune panel turns out to be a useful diagnostic tool for liver diseases, especially PBC in isolation or in overlap syndrome.

Diabetes tipo 1 y Miastenia Gravis / Type-1 Diabetes and Myasthenia Gravis

Introducción: El desarrollo de la tolerancia inmunológica frente a los autoantígenos se denomina autotolerancia. La Diabetes Mellitus tipo 1A (1ADM) es un trastorno metabólico secundario a la destrucción autoinmune de las células beta pancreáticas e insulitis. La miastenia grave (MG) es una enfermedad autoinmune causada por el bloqueo postsináptico de la placa mioneural por AAcs contra los receptores de acetilcolina (ACRA) o contra moléculas de la membrana postsináptica. La asociación entre DM1A y MG se puede observar en el síndrome poliglandular tipo III, caracterizado por enfermedad autoinmune de la glándula tiroides asociada con otras entidades autoinmunes. Método: Reporte de Casos, cuatro pacientes entre 7-19 años, con asociación de MG y DM1A atendidos en el Hospital Garrahan. Conclusión: La Tiroiditis de Hashimoto y la Enfermedad Celíaca son las enfermedades autoinmunes relacionadas más frecuentemente con DM1A en nuestra población. La bibliografía describe la asociación de MG y Tiroiditis de Hashimoto y su coexistencia con DM1A se describe en el Síndrome Poliglandular III. En este trabajo presentamos 4 casos de DM1A asociado con MG fuera de dicho síndrome (AU)

Introduction: The development of immune tolerance to autoantibodies (AAbs) is referred to as self-tolerance. Type 1A Diabetes Mellitus (1ADM) is a metabolic disorder secondary to autoimmune destruction of pancreatic beta cells and insulitis. Myasthenia gravis (MG) is an autoimmune disease caused by postsynaptic blockade of the myoneural plate by AAbs against acetylcholine receptors (Acra) or against postsynaptic membrane molecules. The association between 1ADM and MG may be observed in polyglandular syndrome type III, characterized by autoimmune disease of the thyroid associated with other autoimmune conditions. Methods: Case report; four patients between 7-19 years old, with an association of MG and 1ADM seen at the Garrahan Hospital. Conclusion: Hashimoto's thyroiditis and celiac disease are autoimmune diseases most frequently related to 1ADM in our population. In the literature, the association of MG and Hashimoto's thyroiditis has been described and its coexistence with 1ADM is reported in polyglandular syndrome III. In this study we present 4 cases of 1ADM associated with MG unrelated to this syndrome. (AU)

Increased risk of atrial fibrillation in patients with psoriasis: A meta-analysis of observational studies

Background: Several epidemiological studies have shown that psoriasis increases the risk of developing atrial fibrillation but evidence of this is still scarce. Aims: Our objective was to systematically review, synthesise and critique the epidemiological studies that provided information about the relationship between psoriasis and atrial fibrillation risk. Methods: We searched through PubMed, EMBASE and the bibliographies for articles published between 1 January 2000, and 1 November 2017, that reported on the association between psoriasis and atrial fibrillation. All abstracts, full-text articles and sources were reviewed with duplicate data excluded. Summary relative risks (RRs) with 95% CI were pooled using a random effects model. Results: We identified 252 articles, of these eight unique abstracts underwent full-text review. We finally selected six out of these eight studies comprising 11,187 atrial fibrillation patients. The overall pooled relative risk (RR) of atrial fibrillation was 1.39 (95% CI: 1.257–1.523, P < 0.0001) with significant heterogeneity (I2 = 80.316, Q = 45.723, ?2 = 0.017, P < 0.0001) for the random effects model. In subgroup analysis, the greater risk was found in studies from North America, RR 1.482 (95% CI: 1.119–1.964, P < 0.05), whereas a moderate risk was observed in studies from Europe RR 1.43 (95% CI: 1.269–1.628, P < 0.0001). Limitations: We were only able to include six studies with 11,178 atrial fibrillation patients, because only a few such studies have been published. Conclusion: Our results showed that psoriasis is significantly associated with an increased risk of developing atrial fibrillation. Therefore, physicians should monitor patient’s physical condition on a timely basis.

Serum Vitamin D Level in Psoriasis: A Prospective Study in a Tertiary Care Centre of Eastern India

Background: Psoriasis is a systemic, inflammatory, chronic autoimmune disease characterized by multiple discoid plaques over body with silvery scales associated with cardiovascular diseases, obesity, diabetes mellitus, hypertension, and hyperlipidemia. Recently, association between psoriasis and Vitamin D level has also been reported. Our aim of study was to evaluate the association of vitamin D and its association with the severity of Psoriasis Materials and methods: 60 patients diagnosed with psoriasis, in our outpatient department from January 2021 to December 2021, were included the study. 58 age, gender- and skin phototype- matched healthy controls were included in the study. Results: The serum vitamin D level in patients and in the control group ranged from 7 to 24 ng/ml (mean: 13.04 �32 ng/ml) and from 16 to 65 ng/ml (mean: 23.91�08 ng/ml), respectively. The circulating vit D levels were less in patients compared to control. The analysis showed statistical significance (P< 0.05) between the two groups. Conclusion: Our results showed decreased level of vitamin D in patients suffering from psoriasis when compared to healthy controls. Vitamin D supplementation can be useful in psoriasis management.

Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases / 药物分析学报

As a ligand-dependent transcription factor,retinoid-associated orphan receptor γt(RORyt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the pro-gression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORyt to decrease Th17 cell development and IL-17 production.Several RORyt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORyt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORyt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORyt inhibitors were summarized,with an emphasis on their optimization from lead compounds,ef-ficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.

Application and Effectiveness of Chinese Medicine in Regulating Immune Checkpoint Pathways / 中国结合医学杂志

Immunotherapy targeting immune checkpoint molecules has emerged as a key approach in cancer treatment, representing the forefront of antitumor research. However, studies on immune checkpoint molecules have mainly focused on targeted therapies. Chinese medicine (CM) research as a complementary medicine has revealed that immune checkpoint molecules also undergo disease-specific changes in the context of autoimmune diseases. This review article presents a comprehensive analysis of CM studies on immune checkpoint molecules in the last 5 years, with a focus on their role in different diseases and treatment modalities. CM research predominantly utilizes oral administration of herbal plant extracts or acupuncture techniques, which stimulate the immune system by activating specific acupoints through temperature and needling. In this study, we analyzed the modulation and mechanisms of immune checkpoint molecules associated with different coinhibitory and costimulatory molecules, and reviewed the immune functions of related molecules and CM studies in treating autoimmune diseases and tumors. By summarizing the characteristics and research value of CM in regulating immune checkpoint molecules, this review aims to provide a useful reference for future studies in this field.

Pharmacological importance of Kunxian Capsule in clinical applications and its adverse effects: A review / 中草药·英文版

Kunxian Capsule (KX) is a popular Chinese patent medicine for the treatment of rheumatoid arthritis, nephrotic syndrome, systemic lupus erythematosus, Henoch-Schönlein purpura, ankylosing spondylitis, psoriatic arthritis and eczema. However, there is scarcity of comprehensive information on the significance of KX in the clinical application and its side effects. Hence, it is aimed to provide a review of the significance of KX, with a focus on the pharmacological effects, clinical applications, and its adverse reactions. This review was based on the published literatures in PubMed, China National Knowledge Infrastructure and WanFang database. The articles were collected by two independent authors with no time limits applied until November 30, 2022. The search term includes Kunxian Capsule and/or clinical effect, pharmacology, disease, therapy, adverse effects and quality control. KX has been shown to be effective in the treatment of autoimmune arthritis by inhibiting inflammatory responses and inducing apoptosis. Many studies suggest that KX has anti-inflammatory and analgesic properties that aid in the improvement of joint functions. KX dispels wind, removes dampness, invigorates the kidneys, and promotes blood circulation, thereby curing various diseases. However, studies also suggest KX-related adverse reactions in multiple systems. Overall, this review highlights the scientific basis of KX in curing or preventing various diseases and provides novel insights for further research and clinical applications.

Cellular nanovesicles for therapeutic immunomodulation: A perspective on engineering strategies and new advances

Cellular nanovesicles which are referred to as cell-derived, nanosized lipid bilayer structures, have emerged as a promising platform for regulating immune responses. Owing to their outstanding advantages such as high biocompatibility, prominent structural stability, and high loading capacity, cellular nanovesicles are suitable for delivering various immunomodulatory molecules, such as small molecules, nucleic acids, peptides, and proteins. Immunomodulation induced by cellular nanovesicles has been exploited to modulate immune cell behaviors, which is considered as a novel cell-free immunotherapeutic strategy for the prevention and treatment of diverse diseases. Here we review emerging concepts and new advances in leveraging cellular nanovesicles to activate or suppress immune responses, with the aim to explicate their applications for immunomodulation. We overview the general considerations and principles for the design of engineered cellular nanovesicles with tailored immunomodulatory activities. We also discuss new advances in engineering cellular nanovesicles as immunotherapies for treating major diseases.