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OBJECTIVE: The current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected patients with P. jirovecii PCR-positive results. METHODS: This was a single-center retrospective study between 2019 and 2021. The diagnosis of PJP was based on the following criteria: detection of P. jirovecii in sputum or BAL specimen by qPCR or microscopy; Meet at least two of the three criteria: (1) have respiratory symptoms of cough and/or dyspnea, hypoxia; (2) typical radiological picture findings; (3) receiving a complete PJP treatment. After exclusion, the participants were divided into derivation and validation cohorts. The derivation cohort defined the cut-off value of serum BDG. Then, it was verified using the validation cohort. RESULTS: Two hundred and thirteen HIV-uninfected patients were enrolled, with 159 PJP and 54 P. jirovecii-colonized patients. BDG had outstanding specificity, LR, and PPV for PJP in both the derivation (90.00%, 8.900, and 96.43%) and the validation (91.67%, 9.176, and 96.30%) cohorts at ≥ 117.7 pg/mL. However, it had lower sensitivity and NPV in the derivation cohort (89.01% and 72.97%), which was even lower in the validation cohort (76.47% and 57.89%). Of note, BDG ≥ 117.7 pg/mL has insufficient diagnostic efficacy for PJP in patients with lung cancer, interstitial lung disease (ILD) and nephrotic syndrome. And although lymphocytes, B cells, and CD4+ T cells in PJP patients were significantly lower than those in P. jirovecii-colonized patients, the number and proportion of peripheral blood lymphocytes did not affect the diagnostic efficacy of serum BDG. CONCLUSIONS: Serum BDG ≥ 117.7 pg/mL could effectively distinguish P. jirovecii-colonization from infection in qPCR-positive HIV-uninfected patients with infectious diseases, solid tumors (excluding lung cancer), autoimmune or inflammatory disorders, and hematological malignancies. Of note, for patients with lung cancer, ILD, and nephrotic diseases, PJP should be cautiously excluded at BDG < 117.7 pg/mL.
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Infecciones por VIH , Enfermedades Pulmonares Intersticiales , Neoplasias Pulmonares , Pneumocystis carinii , Neumonía por Pneumocystis , beta-Glucanos , Humanos , Neumonía por Pneumocystis/diagnóstico , Pneumocystis carinii/genética , Glucanos , Estudios Retrospectivos , Infecciones por VIH/complicacionesRESUMEN
Systemic sclerosis (SSc) is a systemic autoimmune disorder that leads to vasculopathy and tissue fibrosis. A lack of reliable biomarkers has been a challenge for clinical diagnosis of the disease. We employed a protein array-based approach to identify and validate SSc-specific autoantibodies. Phase I involved profiled autoimmunity using human proteome microarray (HuProt arrays) with 90 serum samples: 40 patients with SSc, 30 patients diagnosed with autoimmune diseases, and 20 healthy subjects. In Phase II, we constructed a focused array with candidates identified antigens and used this to profile a much larger cohort comprised of serum samples. Finally, we used a western blot analysis to validate the serum of validated proteins with high signal values. Bioinformatics analysis allowed us to identify 113 candidate autoantigens that were significantly associated with SSc. This two-phase strategy allowed us to identify and validate anti-small nuclear ribonucleoprotein polypeptide A (SNRPA) as a novel SSc-specific serological biomarker. The observed positive rate of anti-SNRPA antibody in patients with SSc was 11.25%, which was significantly higher than that of any disease control group (3.33%) or healthy controls (1%). In conclusion, anti-SNRPA autoantibody serves as a novel biomarker for SSc diagnosis and may be promising for clinical applications.
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Enfermedades Autoinmunes , Esclerodermia Sistémica , Humanos , Esclerodermia Sistémica/diagnóstico , Esclerodermia Sistémica/metabolismo , Autoanticuerpos , Biomarcadores/metabolismo , Autoinmunidad , PéptidosRESUMEN
BACKGROUND: Relapsing polychondritis (RP) is an inflammatory disease with significant individual heterogeneity that involves systemic cartilage tissues. This study aimed to perform a bibliometric analysis of RP-related publications to quantitatively assess the scholarly productivity in the field. METHODS: We extracted the RP-related original research articles and reviews published during 1960-2023 from the Web of Science database by using the keyword "relapsing polychondritis." By using R, CiteSpace, VOSviewer, and SCImago Graphica, the bibliometric analysis was performed on the retrieved publications. RESULTS: A total of 1096 articles, consisting of 909 original research articles and 187 reviews, were identified. A mean annual growth rate of 6.71% was found in the number of RP-related publications during 1960-2022. The United States accounted for the highest number of publications (21.9%), exhibited the highest mean citation number per publication (40.7), and engaged in the most frequent academic collaboration. Three clusters of RP-related journals were identified: 1) otology, rhinology, and laryngology; 2) respiratory and radiology medicine; and 3) rheumatology. Journals with a focus on rheumatology issued the most publications, and most of the RP-related publications were from The Journal of Rheumatology (n = 27). Most of these publications were co-authored by Dr. Jean-Charles Piette (n = 19), who also had the highest H-index (13) among all the authors. The co-citation network analysis revealed 11 highly connected clusters of RP research and indicated the "VEXAS Syndrome" as a hotspot. CONCLUSION: This overview of the RP research field comprehensively describes the progress in the field. The number of publications on RP has progressively increased but remains insufficient. The United States and European countries are at the forefront of RP-related research, and the journals related to rheumatology have covered the majority of publications. Additionally, several key topics for future investigations, such as "VEXAS Syndrome," have been identified. Key Points â¢We identified a mean annual growth rate of 6.71% in the number of the RP-related publications during 1960-2022. â¢The United States accounted for the majority of the publications, exhibited the highest mean citation number per publication, and engaged in the most frequent academic collaborations. â¢The journals of the publications were categorized into three clusters of research areas: 1) otology, rhinology, and laryngology; 2) respiratory and radiology medicine; and 3) rheumatology. Journals related to rheumatology issued the most publications, and most of the publications were from The Journal of Rheumatology â¢Most of the publications were co-authored by Dr. Jean-Charles Piette, who also had the highest scientific-research impact among the scholars in the field. â¢The co-citation network analysis revealed 11 highly connected clusters of RP research and indicated the "VEXAS Syndrome" as a key research area.
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Policondritis Recurrente , Humanos , Bibliometría , Bases de Datos Factuales , Europa (Continente)RESUMEN
Behcet's disease (BD) is a chronic inflammatory vasculitis and clinically heterogeneous disorder caused by immunocyte aberrations. Comprehensive research on gene expression patterns in BD illuminating its aetiology is lacking. E-MTAB-2713 downloaded from ArrayExpress was analysed to screen differentially expressed genes (DEGs) using limma. Random forest (RF) and neural network (NN) classification models composed of gene signatures were established using the E-MTAB-2713 training set and subsequently verified using GSE17114. Single sample gene set enrichment analysis was used to assess immunocyte infiltration. After identifying DEGs in E-MTAB-2713, pathogen-triggered, lymphocyte-mediated and angiogenesis- and glycosylation-related inflammatory pathways were discovered to be predominant in BD episodes. Gene signatures from the RF and NN diagnostic models, together with genes enriched in angiogenesis and glycosylation pathways, well discriminated the clinical subtypes of BD manifesting as mucocutaneous, ocular and large vein thrombosis involvement in GSE17114. Moreover, a distinctive immunocyte profile revealed T, NK and dendritic cell activation in BD compared to the findings in healthy controls. Our findings suggested that EPHX1, PKP2, EIF4B and HORMAD1 expression in CD14+ monocytes and CSTF3 and TCEANC2 expression in CD16+ neutrophils could serve as combined gene signatures for BD phenotype differentiation. Pathway genes comprising ATP2B4, MYOF and NRP1 for angiogenesis and GXYLT1, ENG, CD69, GAA, SIGLEC7, SIGLEC9 and SIGLEC16 for glycosylation also might be applicable diagnostic markers for subtype identification.
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Síndrome de Behçet , Humanos , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/genética , Inflamación , Análisis por Micromatrices , Neutrófilos , LinfocitosRESUMEN
[This corrects the article DOI: 10.1016/j.heliyon.2023.e14779.].
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Background: Abnormal lipid metabolism is common in patients with primary biliary cholangitis (PBC). PBC and Sjögren's syndrome (SS) frequently coexist in clinical practice; however, the lipid characteristics of both diseases are unknown. Therefore, we aimed to analyze the plasma lipid profiles of both diseases. Methods: Plasma samples from 60 PBC patients, 30 SS patients, and 30 healthy controls (HC) were collected, and untargeted lipidomics was performed using ultrahigh-performance liquid chromatography high-resolution mass spectrometry. Potential lipid biomarkers were screened through an orthogonal projection to latent structure discriminant analysis and further evaluated using receiver operating characteristic (ROC) analysis. Results: A total of 115 lipids were differentially upregulated in PBC patients compared with HC. Seventeen lipids were positively associated with the disease activity of PBC, and ROC analysis showed that all of these lipids could differentiate between ursodeoxycholic acid (UDCA) responders and UDCA non-responders. The top six lipids based on the area under the curve (AUC) values were glycerophosphocholine (PC) (16:0/16:0), PC (18:1/18:1), PC (42:2), PC (16:0/18:1), PC (17:1/14:0), and PC (15:0/18:1). In comparison with SS, 44 lipids were found to be differentially upregulated in PBC. Additionally, eight lipids were found to have a good diagnostic performance of PBC because of the AUC values of more than 0.9 when identified from SS and HC groups, which were lysophosphatidylcholines (LysoPC) (16:1), PC (16:0/16:0), PC (16:0/16:1), PC (16:1/20:4), PC (18:0/20:3), PC (18:1/20:2), PC (20:0/22:5), and PC (20:1/22:5). Conclusion: Our study revealed differentially expressed lipid signatures in PBC compared with HC and SS. PC is the main lipid species associated with disease activity and the UDCA response in patients with PBC.
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Cirrosis Hepática Biliar , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/complicaciones , Cirrosis Hepática Biliar/diagnóstico , Cirrosis Hepática Biliar/complicaciones , Lipidómica , Ácido Ursodesoxicólico/uso terapéutico , LípidosRESUMEN
Background: Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare disease, whose pathogenesis remains unclear. Here, we conducted untargeted metabolomics and lipidomics to identify seminal plasma signatures of nCHH, and to study the effect of LH and FSH deficiency on semen. Methods: Twenty-five diagnosed patients with nCHH (HH group) and twenty-three healthy participants (HC group) were enrolled. Laboratory parameters, seminal plasma samples and patients' medical data were collected. Untargeted metabolomics and lipidomic profiling were performed using mass spectrometry (MS). Results: The metabolomics profiling are altered among patients with nCHH and healthy controls. There are 160 kinds of differential metabolites and the main different lipid species are TAG, PC, SM and PE. Conclusions: The metabolomics profiles in patients with nCHH changed. We hope that this work provides important insights into the pathophysiology of nCHH.
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OBJECTIVES: An immunoglobulin G4 (IgG4) level above 1350 mg/L is one of the comprehensive criteria for the diagnosis of IgG4-related disease (IgG4-RD). The purpose of this study was to evaluate the differences in IgG4 levels determined using reagents from two main manufacturers and their concordance with clinical diagnosis. METHODS: IgG4 levels were measured in 309 patients, including 146, 40, 42, 41, and 40 patients with untreated IgG4-RD, pancreatic cancer, primary Sjogren syndrome, systemic lupus erythematosus, and idiopathic retroperitoneal fibrosis, respectively, and 141 healthy controls. The results obtained using the Binding Site and Siemens reagents were compared in patients with IgG4-RD. RESULTS: The serum IgG4 level measured using the Siemens reagent was almost two times that measured using the Binding Site reagent. The rate of IgG4-negative patients, which was 19.9% based on measurement using the Binding Site reagent, was only 4.8% based on measurement using the Siemens reagent (p < .001). CONCLUSIONS: There were significant differences in serum IgG4 levels based on commonly used reagents from different manufacturers. The IgG4 cut-off level of 1350 mg/L was not suitable for all detection reagents. Clinicians and patients should be cognizant of these differences associated with the specific detection reagents when evaluating the test results.
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Enfermedad Relacionada con Inmunoglobulina G4 , Fibrosis Retroperitoneal , Humanos , Inmunoglobulina G , Fibrosis Retroperitoneal/diagnósticoRESUMEN
OBJECTIVE: This study was undertaken to elucidate the pathogenesis and heterogeneity of Behçet's disease (BD) involving different organs using in-depth proteomics to identify the biomarkers for clinical assessment and treatment of patients with BD. METHODS: We measured the expression levels of proteins in plasma samples from 98 patients with BD and from 31 healthy controls using our in-depth proteomics platform with a data-independent acquisition mass spectrometer and antibody microarray. We performed bioinformatics analyses of the biologic processes and signaling pathways that were changed in the BD group and constructed a proteomics landscape of organ-resolved BD pathogenesis. We then validated the biomarkers of disease severity and the vascular subset in an independent cohort of 108 BD patients and 29 healthy controls using an enzyme-linked immunosorbent assay. RESULTS: The BD group had 220 differentially expressed proteins, which discriminated between BD patients (88.6%) and healthy controls (95.5%). The bioinformatics analyses revealed different biologic processes associated with BD pathogeneses, including complement activation, wound healing, angiogenesis, and leukocyte-mediated immunity. Furthermore, the constructed proteomics landscape of organ-resolved BD identified proteomics features of BD associated with different organs and protein targets that could be used for the development of therapeutic treatment. Hyaluronic binding protein 2, tenascin, and serpin A3 were validated as potential biomarkers for the clinical assessment of vascular BD and treatment targets. CONCLUSION: Our results provide valuable insight into the pathogenesis of organ-resolved BD in terms of proteomics characteristics and potential biomarkers for clinical assessment and potential therapies for vascular BD.
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Síndrome de Behçet , Productos Biológicos , Humanos , Proteínas Portadoras , Proteómica , AnticuerposRESUMEN
OBJECTIVES: The objective of the current study was to detect plasma profiles of inflammatory cytokines for determining potential biomarkers indicating cancer presence among the anti-TIF1-γ antibody-positive dermatomyositis (DM) patients. METHODS: Twenty-seven cancer-associated anti-TIF1-γ antibody-positive DM (Cancer TIF1-γ-DM) patients were compared with 20 anti-TIF1-γ antibody-positive DM patients without cancer (Non-cancer TIF1-γ-DM) and 10 healthy controls (HC). The plasma levels of 17 cytokines were determined using the Luminex 200 system. The ability of plasma VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ levels to distinguish the presence of cancer was evaluated through the area under the curve (AUC) analysis. Potential protein interactions of TIF1-γ and the five cytokines were analyzed using the STRING database. RESULTS: VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ plasma levels were significantly higher in the Cancer TIF1-γ-DM group, especially those without any anticancer treatment, than those in the non-cancer TIF1-γ-DM and HC groups. Meanwhile, anti-TIF1-γ antibody and the five cytokines could distinguish cancer presence in anti-TIF1-γ antibody-positive DM patients. The STRING network indicated that TIF1-γ potentially interacted with the cytokines. Positive correlations of VEGF-A among CCL2, IL-6, and IFN-γ and between IFN-γ and IL-6 were observed in Cancer TIF1-γ-DM patients. VEGF-A, TNF-α, CCL2, and IL-6 were positively associated with muscle-associated enzymes among the Cancer TIF1-γ-DM patients. CONCLUSION: The present study identified VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ as significant potential biomarkers indicating the presence of cancer and demonstrated a more detailed cytokine profile during diagnosis. These biomarkers could provide better screening strategies and insight into the Cancer TIF1-γ-DM pathogenesis. Key Points ⢠VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ are potential biomarkers of cancer in cancer-associated anti-TIF1-γ antibody-positive dermatomyositis. Potential pathogenic molecular mechanism of the cancer-associated anti-TIF1-γ antibody-positive dermatomyositis.
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Dermatomiositis , Neoplasias , Humanos , Dermatomiositis/complicaciones , Dermatomiositis/diagnóstico , Factor de Necrosis Tumoral alfa , Interleucina-6 , Factor A de Crecimiento Endotelial Vascular , Autoanticuerpos , Neoplasias/complicaciones , Citocinas , Biomarcadores , Interferón gamma , Quimiocina CCL2RESUMEN
BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disease with ethnic differences. Single-nucleotide polymorphisms (SNPs) in the ARID3A, CXCR5, and TNFSF8 genes have been reported to be associated with various autoimmune diseases. The aim of this study was to investigate the association between these SNPs and susceptibility to SSc in a Chinese Han population. METHODS: A case-control study was conducted in 342 patients with SSc and 694 ethnically matched healthy controls. SNPs in ARID3A, CXCR5, and TNFSF8 were genotyped using a Sequenom MassArray iPLEX system, and allele association analyses were performed using the PLINK v1.90 software. RESULTS: Our study demonstrated that the ARID3A rs10415976 G and CXCR5 rs77871618 T alleles were suggestively associated with patients with SSc (P = 0.049 and P = 0.024, respectively) and TNFSF8 rs1555457 T allele was strongly associated with SSc (P = 0.003). Patients carrying the ARID3A rs350146 TT and TNFSF8 rs1555457 TT genotypes had a significant increased risk of SSc (P = 0.03 and P = 0.004, respectively). Moreover, rs10415976, rs77871618, and rs1555457 were associated with SSc in an additive genetic model (P < 0.05). rs62132345 and rs1555457 were associated with SSc in the dominant genetic model (P < 0.05). rs350146 was associated with SSc in the recessive genetic model (P = 0.029). CONCLUSIONS: ARID3A rs10415976, ARID3A rs350146, and CXCR5 rs77871618 were suggestively associated with SSc and TNFSF8 rs1555457 was strongly associated with SSc in the Chinese Han population in this study. Key Points ⢠This case-control study determined that ARID3A rs10415976, ARID3A rs350146 and CXCR5 rs77871618 were suggestively associated with SSc and TNFSF8 rs1555457 was strongly associated with SSc in the Chinese Han population. ⢠The differences in these results compared with previous studies may be a result of ethnic and racial differences.
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Predisposición Genética a la Enfermedad , Esclerodermia Sistémica , Humanos , Alelos , Estudios de Casos y Controles , China/epidemiología , Proteínas de Unión al ADN/genética , Pueblos del Este de Asia , Frecuencia de los Genes , Genotipo , Polimorfismo de Nucleótido Simple , Esclerodermia Sistémica/genética , Factores de Transcripción/genéticaRESUMEN
BACKGROUND: The pathogenesis of immunoglobulin G4-related disease (IgG4-RD) remains unclear. IgG4-RD often mimics other diseases, including pancreatic cancer (PC) and Sjogren's syndrome (SS), which may easily lead to misdiagnosis. This study was performed to explore the metabolite changes and potential biomarkers of IgG4-RD and other misdiagnosed diseases. METHODS: Untargeted liquid chromatography-tandem mass spectrometry metabolomics profiling of plasma samples from a cohort comprising healthy controls (HCs) and patients with IgG4-RD (n = 87), PC (n = 33), and SS (n = 31) was performed. A random forest machine learning model was used to verify the relevance of the identified metabolites in the diagnosis of different diseases and the prediction of disease prognosis. RESULTS: The ATP-binding cassette transporter pathway was found to be most closely related to IgG4-RD, which was significantly up-regulated in the IgG4-RD group than in all the matched groups. Five metabolites were proved to be valuable biomarkers for IgG4-RD. Caftaric acid, maltotetraose, D-glutamic acid, 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphoserine, and hydroxyproline were useful in distinguishing between IgG4-RD, PC, SS, and HC [area under the curve (AUC) = 1]. A combination of phenylalanine betaine, 1-(1z-hexadecenyl)-sn-glycero-3-phosphocholine, Pi 40:8, uracil, and N1-methyl-2-pyridone-5-carboxamide showed a moderate value in predicting relapse in patients with IgG4-RD (AUC = 0.8). CONCLUSIONS: Our findings revealed the metabolite changes of IgG4-RD and provide new insights for deepening our understanding of IgG4-RD despite the lack of validation in external cohorts. Metabolomic biomarkers have significance in the clinical diagnosis and disease prognosis of IgG4-RD.
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Enfermedad Relacionada con Inmunoglobulina G4 , Neoplasias Pancreáticas , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/metabolismo , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Pronóstico , Biomarcadores , Neoplasias Pancreáticas/diagnósticoRESUMEN
Background: Finasteride is widely used in the treatment of benign prostatic hyperplasia (BPH) and androgenic alopecia (AGA). Post-finasteride syndrome (PFS) is a spectrum of persistent symptoms reported by some patients after treatment with finasteride for androgenetic alopecia. These patients show many abnormal clinical manifestations, including psychological disorders (depression and anxiety, among others) and sexual dysfunction. However, there is insufficient research on the persistent severe side effects in young male patients with PFS, and the underlying mechanism of PFS has not been fully elucidated. Growing evidence highlights the relevance of genetic variants and their associated responses to drugs. Therefore, we performed next-generation sequencing (NGS) in our study of PFS. Case Description: Here, we enrolled three young male patients aged 20-30 years with a PFS duration of 1-3 years and analyzed their clinical and genetic information. PFS patients suffered from erectile dysfunction (ED), anxiety, feelings of isolation, and insomnia. Variants in genes, including CA8, VSIG10L2, HLA-B, KRT38 and HLA-DRB1, were detected, and these genes represent potential risk genes. Conclusions: PFS, commonly observed in young men, has certain clinical manifestations, mainly psychological disorders and abnormal sexual functions. Young men who may take finasteride therapy for hair loss should receive consultation services and be informed of possible future harms. Psychological screening is an important method to reduce the occurrence of PFS. At present, the underlying mechanism of PFS is not very clear, and more research is needed to improve the understanding of the disease. Some genes are abnormal in PFS patients, suggesting that clinical and genetic evaluation might be needed before the prescription of 5α-reductase inhibitors. With research progress, genetic screening may be a promising way to avoid the harmful effects of finasteride in people with related genetic risk factors.
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BACKGROUND: Anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (MDA5+ DM) is significantly associated with interstitial lung disease (ILD), especially rapidly progressive ILD (RPILD) due to poor prognosis, resulting in high mortality rates. However, the pathogenic mechanism of MDA5+ DM-RPILD is unclear. Although some MDA5+ DM patients have a chronic course of ILD, many do not develop RPILD. Therefore, the related biomarkers for the early diagnosis, disease activity monitoring, and prediction of the outcome of RPILD in MDA5+ DM patients should be identified. Blood-based biomarkers are minimally invasive and can be easily detected. METHODS: Recent relative studies related to blood biomarkers in PubMed were reviewed. RESULTS: An increasing number of studies have demonstrated that dysregulated expression of blood biomarkers related to ILD such as ferritin, Krebs von den Lungen-6 (KL-6), surfactant protein-D (SP-D), and cytokines, and some tumor markers in MDA5+ DM may provide information in disease presence, activity, treatment response, and prognosis. These studies have highlighted the great potentials of blood biomarker values for MDA5+ DM-ILD and MDA5+ DM-RPILD. This review provides an overview of recent studies related to blood biomarkers, besides highlighted protein biomarkers, including antibody (anti-MDA5 IgG subclasses and anti-Ro52 antibody), genetic (exosomal microRNAs and neutrophil extracellular traps related to cell-free DNA), and immune cellular biomarkers in MDA5+ DM, MDA5+ DM-ILD, and MDA5+ DM-RPILD patients, hopefully elucidating the pathogenesis of MDA5+ DM-ILD and providing information on the early diagnosis, disease activity monitoring, and prediction of the outcome of the ILD, especially RPILD. CONCLUSIONS: Therefore, this review may provide insight to guide treatment decisions for MDA5+ DM-RPILD patients and improve outcomes.
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Dermatomiositis , Enfermedades Pulmonares Intersticiales , Humanos , Helicasa Inducida por Interferón IFIH1 , Autoanticuerpos , Progresión de la Enfermedad , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico , Biomarcadores , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVES: IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder with heterogeneous manifestations. This study aimed to investigate the utility of human epididymis protein 4 (HE4) as a potential clinical biomarker of fibrosis in IgG4-RD. METHODS: Plasma HE4 levels were estimated in 136 patients with IgG4-RD and 73 healthy individuals (controls) by electrochemical luminescence. HE4 expression levels and the degree of fibrosis in pancreatic tissues from 15 patients with IgG4-RD and 10 controls were compared using immunohistochemistry and Masson trichrome staining. Correlation between HE4 levels and laboratory parameters was determined, and the efficacy of HE4 as a biomarker of fibrosis and prognosis in IgG4-RD was also evaluated. RESULTS: Plasma HE4 levels were significantly higher in patients with IgG4-RD compared with controls. Optimal HE4 cut-off value for identifying patients with IgG4-RD was determined to be 50.8 pmol/L with an AUC (area under curve) of 0.791. HE4 levels were positively correlated with diverse laboratory parameters, and indicators of organ function impairment. Additionally, HE4 was highly expressed in the affected organs in patients with IgG4-RD and its plasma levels were closely correlated with degree of fibrosis, indicating the utility of HE4 in assessing internal organ damage and fibrosis. Further analysis showed that patients in the HE4 high expression group had poor prognosis. CONCLUSIONS: Our results demonstrate that HE4 can be used as a biomarker for IgG4-RD as it is correlated with diverse baseline clinical features, internal organ damage and degree of fibrosis in affected organs, and can predict poor prognosis.
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Enfermedad Relacionada con Inmunoglobulina G4 , Biomarcadores , Fibrosis , Humanos , Inmunoglobulina G , PronósticoRESUMEN
Innate lymphoid cells (ILCs), a novel group of innate immune cells, play a key role in the early immune response via rapidly reacting to signals expressed by tissue-resident cells. ILCs contribute to some autoimmune diseases. We aim to investigate the proportions of circulating ILC subgroups in patients with primary biliary cholangitis (PBC). Overall, 48 patients with PBC and 24 healthy controls (HCs) were enrolled. Circulating ILCs and cytokine production were detected by flow cytometry. The proportions of total ILCs, ILC precursors (ILCPs) and ILCP/ILC2 ratio increased and that of ILC2s decreased in patients with PBC. ILC2 proportion was negatively correlated with gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The proportion of ILCPs and ILCP/ILC2 ratio were positively correlated with alkaline phosphatase, GGT, ALT and AST. ILC2 proportion was significantly decreased in the ursodeoxycholic acid (UDCA) -non-responder group compared with the UDCA-responder group, whereas the proportion of ILCPs and ILCP/ILC2 were ratio significantly increased. The proportions of CD38+ ILC2s, CD38+ ILCPs, CD45RO+ ILC2s and CD45RO+ ILCPs were significantly higher in patients with PBC than in HCs. Levels of IL-17A producing ILCs were higher in patients with PBC than in HCs. PBC is accompanied by alterations in circulating ILCs. The proportions of ILC2s, ILCPs, and ILCP/ILC2 ratio were associated with the PBC disease activity. The proportions of ILCPs and ILCP/ILC2 ratio may reflect the UDCA treatment failure in patients with PBC. ILC2s and ILCPs from patients with PBC get activated, these cells may be involved in the pathogenesis of PBC.
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Inmunidad Innata , Cirrosis Hepática Biliar , Citometría de Flujo , Humanos , Cirrosis Hepática Biliar/tratamiento farmacológico , LinfocitosRESUMEN
A comprehensive analysis of the humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential in understanding COVID-19 pathogenesis and developing antibody-based diagnostics and therapy. In this work, we performed a longitudinal analysis of antibody responses to SARS-CoV-2 proteins in 104 serum samples from 49 critical COVID-19 patients using a peptide-based SARS-CoV-2 proteome microarray. Our data show that the binding epitopes of IgM and IgG antibodies differ across SARS-CoV-2 proteins and even within the same protein. Moreover, most IgM and IgG epitopes are located within nonstructural proteins (nsps), which are critical in inactivating the host's innate immune response and enabling SARS-CoV-2 replication, transcription, and polyprotein processing. IgM antibodies are associated with a good prognosis and target nsp3 and nsp5 proteases, whereas IgG antibodies are associated with high mortality and target structural proteins (Nucleocapsid, Spike, ORF3a). The epitopes targeted by antibodies in patients with a high mortality rate were further validated using an independent serum cohort (n = 56) and using global correlation mapping analysis with the clinical variables that are associated with COVID-19 severity. Our data provide fundamental insight into humoral immunity during SARS-CoV-2 infection. SARS-CoV-2 immunogenic epitopes identified in this work could also help direct antibody-based COVID-19 treatment and triage patients.
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Anticuerpos Antivirales/inmunología , COVID-19/inmunología , Inmunidad Humoral , SARS-CoV-2/inmunología , Proteínas no Estructurales Virales/inmunología , COVID-19/mortalidad , Enfermedad Crítica , Supervivencia sin Enfermedad , Epítopos/inmunología , Femenino , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Masculino , Análisis por Matrices de Proteínas , Tasa de SupervivenciaRESUMEN
Objectives: Systemic sclerosis (SSc) is an uncommon autoimmune disease that varies with ethnicity. Single nucleotide polymorphisms (SNPs) in the GTFSI, NFKB1, and TYK2 genes have been reported to be associated with SSc in other populations and in individuals with various autoimmune diseases. This study aimed to investigate the association between these SNPs and susceptibility to SSc in a Chinese Han population. Method: A case-control study was performed in 343 patients with SSc and 694 ethnically matched healthy controls. SNPs in GTF2I, NFKB1, and TYK2 were genotyped using a Sequenom MassArray iPLEX system. Association analyses were performed using PLINK v1.90 software. Result: Our study demonstrated that the GTF2I rs117026326 T allele and the GTF2I rs73366469 C allele were strongly associated with patients with SSc (P = 6.97E-10 and P = 1.33E-08, respectively). Patients carrying the GTF2I rs117026326 TT genotype and the GTF2I rs73366469 CC genotype had a strongly increased risk of SSc (P = 6.25E-09 and P = 1.67E-08, respectively), and those carrying the NFKB1 rs1599961 AA genotype had a suggestively significantly increased risk of SSc (P = 0.014). Moreover, rs117026326 and rs73366469 were associated with SSc in different genetic models (additive model, dominant model, and recessive model) (P < 0.05) whereas rs1599961 was associated with SSc in the dominant genetic model but not in the addictive and recessive models (P = 0.0026). TYK2 rs2304256 was not significantly associated with SSc in this study. Conclusion: GTF2I rs117026326 and rs73366469 SNPs were strongly associated with SSc in this Chinese Han population. NFKB1 rs1599961 showed a suggestive association with SSc, and no significant association was found between TYK2 rs2304256 and SSc in this Chinese Han population.
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Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad/genética , Subunidad p50 de NF-kappa B/genética , Polimorfismo de Nucleótido Simple/inmunología , Esclerodermia Sistémica/genética , TYK2 Quinasa/genética , Factores de Transcripción TFII/genética , Enfermedades Autoinmunes/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Background: Autoimmune diseases (ADs) are characterized by immune-mediated tissue damage, in which angiogenesis is a prominent pathogenic mechanism. Vascular endothelial growth factor (VEGF), an angiogenesis modulator, is significantly elevated in several ADs including rheumatoid arthritis (RA), systemic sclerosis (SSc), and systemic lupus erythematosus (SLE). We determined whether circulating VEGF levels were associated with ADs based on pooled evidence. Methods: The analyses included 165 studies from the PubMed, EMBASE, Cochrane Library, and Web of Science databases and fulfilled the study criteria. Comparisons of circulating VEGF levels between patients with ADs and healthy controls were performed by determining pooled standard mean differences (SMDs) with 95% confidence intervals (CIs) in a random-effect model using STATA 16.0. Subgroup, sensitivity, and meta-regression analyses were performed to determine heterogeneity and to test robustness. Results: Compared with healthy subjects, circulating VEGF levels were significantly higher in patients with SLE (SMD 0.84, 95% CI 0.25-1.44, P = 0.0056), RA (SMD 1.48, 95% CI 0.82-2.15, P <0.0001), SSc (SMD 0.56, 95% CI 0.36-0.75, P <0.0001), Behcet's disease (SMD 1.65, 95% CI 0.88-2.41, P <0.0001), Kawasaki disease (SMD 2.41, 95% CI 0.10-4.72, P = 0.0406), ankylosing spondylitis (SMD 0.78, 95% CI 0.23-1.33, P = 0.0052), inflammatory bowel disease (SMD 0.57, 95% CI 0.43-0.71, P <0.0001), psoriasis (SMD 0.98, 95% CI 0.62-1.34, P <0.0001), and Graves' disease (SMD 0.69, 95% CI 0.20-1.19, P = 0.0056). Circulating VEGF levels correlated with disease activity and hematological parameters in ADs. Conclusion: Circulating VEGF levels were associated with ADs and could predict disease manifestations, severity and activity in patients with ADs. Systematic Review Registration: PROSPERO, identifier CRD42021227843.