Antineutrophil cytoplasmic antibody is an independent risk factor in rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVES: This study aimed to investigate the clinical relevance of antineutrophil cytoplasmic antibody (ANCA) in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: Detailed clinical records of rheumatoid arthritis (RA) patients who underwent ANCA screening tests were collected. ANCA measurements were determined by indirect immunofluorescence assay (IIF) and enzyme-linked immunosorbent assay (ELISA). Clinical characteristics were compared between ANCA-positive and ANCA-negative groups, and multivariable logistic models were used to evaluate the independent association of ANCA with ILD in RA patients. RESULTS: The prevalence of ANCA by IIF was significantly higher in RA-ILD patients compared to those with RA without ILD (31.7 % vs. 19.5 %, p < 0.001). RA-ILD patients positive for ANCA exhibited elevated levels of inflammatory markers and greater disease activity, and showed more severe impairment of lung function compared to ANCA-negative RA-ILD patients. Multivariable logistic regression analysis revealed an independent association of ANCA, especially pANCA, with RA-ILD. ANCA specificities for BPI, elastase, and cathepsin-G were found in 15.6 % of RA-ILD patients; the specificities for most others remain unknown. CONCLUSIONS: The findings suggest a potential role for ANCA/pANCA in stratifying the risk of RA and provide supplementary information to the existing clinically available assays. This additional information may be valuable in identifying RA patients who require further investigations for RA-ILD, such as high-resolution computed tomography (HRCT). These results emphasize the potential clinical relevance of ANCA in the context of RA-ILD.

Viral communities in a pH>10 serpentinite-like environment: insight into diversity and potential roles in modulating the microbiomes by bioactive vitamin B9 synthesis.

Viral communities exist in a variety of ecosystems and play significant roles in mediating biogeochemical processes, whereas viruses inhabiting strongly alkaline geochemical systems remain underexplored. In this study, the viral diversity, potential functionalities, and virus-host interactions in a strongly alkaline environment (pH = 10.4-12.4) exposed to the leachates derived from the serpentinization-like reactions of smelting slags were investigated. The viral populations (e.g., Herelleviridae, Queuovirinae, and Inoviridae) were closely associated with the dominating prokaryotic hosts (e.g., Meiothermus, Trueperaceae, and Serpentinomonas) in this ultrabasic environment. Auxiliary metabolic genes (AMGs) suggested that viruses may enhance hosts' fitness by facilitating cofactor biosynthesis, hydrogen metabolism, and carbon cycling. To evaluate the activity of synthesis of essential cofactor vitamin B9 by the viruses, a viral folA (vfolA) gene encoding dihydrofolate reductase (DHFR) was introduced into a thymidine-auxotrophic strain Escherichia coli MG1655 ΔfolA mutant, which restored the growth of the latter in the absence of thymidine. Notably, the homologs of the validated vDHFR were globally distributed in the viromes across various ecosystems. The present study sheds new light on the unique viral communities in hyperalkaline ecosystems and their potential beneficial impacts on the coexisting microbial consortia by supplying essential cofactors. IMPORTANCE: This study presents a comprehensive investigation into the diversity, potential functionalities, and virus-microbe interactions in an artificially induced strongly alkaline environment. Functional validation of the detected viral folA genes encoding dihydrofolate reductase substantiated the synthesis of essential cofactors by viruses, which may be ubiquitous, considering the broad distribution of the viral genes associated with folate cycling.

NK Cell Mitochondrial Membrane Potential-Associated Model Predicts Outcomes in Critically Ill Patients with COVID-19.

Purpose: This study investigated potential predictive models associated with natural killer (NK) cell mitochondrial membrane potential (MMP or ΔΨm) in predicting death among critically ill patients with COVID-19. Patients and Methods: We included 97 patients with COVID-19 of different severities attending Peking Union Medical College Hospital from December 2022 to January 2023. Patients were divided into three groups according to oxygen and mechanical ventilation use during specimen collection and were followed for survival and death at 3 months. The lymphocyte subpopulation MMP was detected via flow cytometry. We constructed a joint diagnostic model by integrating identified key indicators and generating receiver operating curves (ROCs) and evaluated its predictive performance for mortality risk in critically ill patients. Results: The NK-cell MMP median fluorescence intensity (MFI) was significantly lower in critically ill patients who died from COVID-19 (p<0.0001) and significantly and positively correlated with D-dimer content in critically ill patients (r=0.56, p=0.0023). The random forest model suggested that fibrinogen levels and NK-cell MMP MFI were the most important indicators. Integrating the above predictive models for the ROC yielded an area under the curve of 0.94. Conclusion: This study revealed the potential of combining NK-cell MMP with key clinical indicators (D-dimer and fibrinogen levels) to predict death among critically ill patients with COVID-19, which may help in early risk stratification of critically ill patients and improve patient care and clinical outcomes.

Cystic intracranial solitary fibrous tumor: a case report.

Solitary fibrous tumor (SFT) is a rare spindle cell tumor originating from mesenchymal tissue, and even rarer when it occurs intracranially. This case report described a 42-year-old man who presented with headache and limb weakness for more than 10 days. Magnetic resonance imaging (MRI) showed a well-defined multicompartmental cystic space-occupying lesion in the left occipital region, with surrounding edema and a compressed left lateral ventricle, the mass growing across the cerebellar vermis, which was initially diagnosed as hemangioblastoma. Neurosurgery was utilized to successfully remove the mass, and intracranial solitary fibrous tumor (ISFT) was identified by postoperative pathological analysis. Here, this article describes the imaging manifestations and pathologic features of a case of cystic intracranial solitary fibrous tumor, aiming to improve the understanding and diagnosis of this disease in order to provide an accurate therapy plan.

Impaired acute-phase humoral immunity is the major factor predicting unfavorable outcomes in multiple myeloma patients with SARS-CoV-2 Omicron variants outbreak infection.

At the end of 2022, a huge tide of SARS-CoV-2 infection mainly Omicron BA.4/5 developed in China. Multiple myeloma (MM) patients suffered cancer deterioration and mortality from COVID-19, yet profound analyses of Omicron variants-induced immunity function are scarce. We presented a longitudinal study in 218 MM patients and 73 healthy controls (HCs), reporting the prognostic factors and dynamic humoral and cellular immune responses. Neutralizing antibody and interferon γ ELISpot assay of SARS-CoV-2 was tested at three time points: 2-4, 8-10, and 14-16 weeks after infections. Our data showed older age, active MM, relapsed/refractory MM (R/RMM), immunotherapy, comorbidity, and non-vaccination were risk factors associated with hospitalization. Severe humoral immunity impairment within 2-4 weeks was especially seen in patients with unvaccinated, older age, immunotherapy, R/RMM and comorbidities, while T-cell response was relatively intact. Although antibodies of Omicron variants reached positive levels in MM patients at 8-10 weeks, half lost effective antibody protection at 14-16 weeks. However, most seronegative patients (76.2% at 2-4 weeks, 83.3% at 8-10 weeks) could develop effective T-cell response. Notably, the inactivated wild-type vaccinated patients exhibited weaker humoral and cellular immunity only at 2-4 weeks, escalating to similar levels as those in HCs later. Our findings indicate impairment of humoral immunity at acute-phase after infection is the major factor correlated with hospitalization. One-month suspension of immune therapy is suggested to prevent serious infection. These results confirm the value of inactivated vaccine, but indicate the need for additional booster at 14-16 weeks after infection for high-risk MM population.

DNA methylation patterns in patients with asthenospermia and oligoasthenospermia.

BACKGROUND: Spermatogenesis is a highly regulated and complex process in which DNA methylation plays a crucial role. This study aimed to explore the differential methylation profiles in sperm DNA between patients with asthenospermia (AS) and healthy controls (HCs), those with oligoasthenospermia (OAS) and HCs, and patients with AS and those with OAS. RESULTS: Semen samples and clinical data were collected from five patients with AS, five patients with OAS, and six age-matched HCs. Reduced representation bisulfite sequencing (RRBS) was performed to identify differentially methylated regions (DMRs) in sperm cells among the different types of patients and HCs. A total of 6520, 28,019, and 16,432 DMRs were detected between AS and HC, OAS and HC, and AS and OAS groups, respectively. These DMRs were predominantly located within gene bodies and mapped to 2868, 9296, and 9090 genes in the respective groups. Of note, 12, 9, and 8 DMRs in each group were closely associated with spermatogenesis and male infertility. Furthermore, BDNF, SMARCB1, PIK3CA, and DDX27; RBMX and SPATA17; ASZ1, CDH1, and CHDH were identified as strong differentially methylated candidate genes in each group, respectively. Meanwhile, the GO analysis of DMR-associated genes in the AS vs. HC groups revealed that protein binding, cytoplasm, and transcription (DNA-templated) were the most enriched terms in the biological process (BP), cellular component (CC), and molecular function (MF), respectively. Likewise, in both the OAS vs. HC and AS vs. OAS groups, GO analysis revealed protein binding, nucleus, and transcription (DNA-templated) as the most enriched terms in BP, CC, and MF, respectively. Finally, the KEGG analysis of DMR-annotated genes and these genes at promoters suggested that metabolic pathways were the most significantly associated across all three groups. CONCLUSIONS: The current study results revealed distinctive sperm DNA methylation patterns in the AS vs. HC and OAS vs. HC groups, particularly between patients with AS and those with OAS. The identification of key genes associated with spermatogenesis and male infertility in addition to the differentially enriched metabolic pathways may contribute to uncovering the potential pathogenesis in different types of abnormal sperm parameters.

Significance of immunoglobulins synthesis with central nervous system involvement in Neuro-Behçet's disease.

OBJECTIVES: Demyelination and immunocyte-infiltrated lesions have been found in neuro-Behçet's disease (NBD) pathology. Lacking satisfying laboratory biomarkers in NBD impedes standard clinical diagnostics. We aim to explore the ancillary indicators for NBD diagnosis unveiling its potential etiology. METHODS: 28 NBD with defined diagnosis, 29 patients with neuropsychiatric lupus erythematosus, 30 central nervous system idiopathic inflammatory demyelination diseases (CNS-IIDD), 30 CNS infections, 30 cerebrovascular diseases, and 30 noninflammatory neurological diseases (NIND) were retrospectively enrolled. Immunoglobulins (Ig) in serum and cerebral spinal fluid (CSF) were detected by immunonephelometry and myelin basic protein (MBP) by quantitative enzyme-linked immunosorbent assay. RESULTS: IgA index is almost twice enhanced in NBD than NIND with an accuracy of 0.8488 in differential diagnosis, the sensitivity and specificity of which were 75.00 % and 90.00 % when the cutoff was > 0.6814. The accuracy of CSF Ig and quotient of Ig all exceed 0.90 in discerning NBD with damaged and intact blood-brain barrier (BBB). Clustering analyses divided NBD into two different phenotypes: one with BBB damage has lower Ig synthesis, the other with extra-synthesis in parenchymal sites but with intact BBB. MBP index is significantly correlated with kappa (KAP) index and lambda (LAM) index (r = 0.358, 0.575, P < 0.001), hinting the NBD pathogenesis of CNS demyelination in triggering excessive intrathecal Ig productions and humoral responses. CONCLUSIONS: IgA index acts as a potential diagnostic indicator in differentiating NBD from NIND and CNS-IIDD. Excessive immunoglobulin production induced by CNS inflammation and demyelination might be latent immunopathogenesis of NBD.

Acceptance, safety, and immunogenicity of a booster dose of inactivated SARS-CoV-2 vaccine in patients with primary biliary cholangitis.

Inactivated coronavirus disease 2019 (COVID-19) vaccines showed impaired immunogenicity in some autoimmune diseases, but it remains unclear in primary biliary cholangitis (PBC). This study aimed to explore the antibody response to the inactivated COVID-19 vaccine in individuals with PBC, as well as to evaluate coverage, safety, and attitudes toward the COVID-19 vaccine among them. Two cohorts of patients with PBC were enrolled in this study. One cohort was arranged to evaluate the immunogenicity of the inactivated COVID-19 vaccine, another cohort participated in an online survey. The titers of the anti-receptor-binding domain (RBD)-specific immunoglobulin G (IgG), neutralizing antibody (NAb) toward severe acute respiratory syndrome coronavirus 2 wild-type, and NAb toward Omicron BA.4/5 subvariants were detected to assess antibody response from the vaccine. After booster vaccination for more than six months, patients with PBC had significantly lowered levels of anti-RBD-specific IgG compared to HCs, and the inhibition rates of NAb toward wild-type also declined in individuals with PBC. The detected levels of NAb toward Omicron BA.4/5 were below the positive threshold in patients with PBC and HCs. Laboratory parameters did not significantly correlate with any of the three antibodies. The online survey revealed that 24% of patients with PBC received three COVID-19 vaccines, while 63% were unimmunized. Adverse effect rates after the first, second, and third vaccine doses were 6.1%, 10.3%, and 9.5%, respectively. Unvaccinated patients with PBC were more worried about the safety of the vaccine than those who were vaccinated (P = 0.004). As a result, this study fills the immunological assessment gap in patients with PBC who received inactivated COVID-19 vaccines.

Omicron BA.4/5 neutralization and cell-mediated immune responses in relation to baseline immune status and breakthrough infection among PLWH: A follow-up cohort study.

There is a paucity of data on hybrid immunity (vaccination plus breakthrough infection [BI]), especially cell-mediated responses to Omicron among immunosuppressed patients. We aim to investigate humoral and cellular responses to Omicron BA.4/5 among people living with HIV (PLWH) with/without BIs, the most prevalent variant of concern after the reopening of China. Based on our previous study, we enrolled 77 PLWH with baseline immune status of severe acute respiratory syndrome coronavirus 2 specific antibodies after inactivated vaccination. "Correlates of protection," including serological immunoassays, T cell phenotypes and memory B cells (MBC) were determined in PLWH without and with BI, together with 16 PLWH with reinfections. Higher inhibition rate of neutralizing antibodies (NAb) against BA.4/5 was elicited among PLWH with BI than those without. Omicron-reactive IL4+ CD8+ T cells were significantly elevated in PLWH experienced postvaccine infection contrasting with those did not. NAb towards wild type at baseline was associated with prolonged negative conversion time for PLWH whereas intermediate MBCs serve as protecting effectors. We uncovered that hybrid immunity intensified more protection on BA.4/5 than vaccination did. Strengthened surveillance on immunological parameters and timely clinical intervention on PLWH deficient in protection would reduce the severity and mortality in the context of coexistence with new Omicron subvariants.

COVID-19 vaccination willingness among people living with HIV in Shijiazhuang, China: a cross-sectional survey.

Objectives: The COVID-19 pandemic imposed an enormous disease and economic burden worldwide. SARS-CoV-2 vaccination is essential to containing the pandemic. People living with HIV (PLWH) may be more vulnerable to severe COVID-19 outcomes; thus, understanding their vaccination willingness and influencing factors is helpful in developing targeted vaccination strategies. Methods: A cross-sectional study was conducted between 15 June and 30 August 2022 in Shijiazhuang, China. Variables included socio-demographic characteristics, health status characteristics, HIV-related characteristics, knowledge, and attitudes toward COVID-19 vaccination and COVID-19 vaccination status. Multivariable logistic regression was used to confirm factors associated with COVID-19 vaccination willingness among PLWH. Results: A total of 1,428 PLWH were included, with a 90.48% willingness to receive the COVID-19 vaccination. PLWH were more unwilling to receive COVID-19 vaccination for those who were female or had a fair/poor health status, had an allergic history and comorbidities, were unconvinced and unsure about the effectiveness of vaccines, were unconvinced and unsure about the safety of vaccines, were convinced and unsure about whether COVID-19 vaccination would affect ART efficacy, or did not know at least a type of domestic COVID-19 vaccine. Approximately 93.00% of PLWH have received at least one dose of the COVID-19 vaccine among PLWH, and 213 PLWH (14.92%) reported at least one adverse reaction within 7 days. Conclusion: In conclusion, our study reported a relatively high willingness to receive the COVID-19 vaccination among PLWH in Shijiazhuang. However, a small number of PLWH still held hesitancy; thus, more tailored policies or guidelines from the government should be performed to enhance the COVID-19 vaccination rate among PLWH.

Immune cells and related cytokines in dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a non-ischemic cardiomyopathy involving one or more underlying etiologies. It is characterized by structural and functional dysfunction of the myocardium, potentially leading to fibrosis and ventricular remodeling, and an elevated risk of heart failure (HF). Although the pathogenesis of DCM remains unknown, compelling evidence suggests that DCM-triggered immune cells and inflammatory cascades play a crucial role in the occurrence and development of DCM. Various factors are linked to myocardial damage, inducing aberrant activation of the immune system and sustained inflammatory responses in DCM. The investigation of the immunopathogenesis of DCM also contributes to discovering new biomarkers and therapeutic targets. This review examines the roles of immune cells and related cytokines in DCM pathogenesis and explores immunotherapy strategies in DCM.

ChIP-seq analysis found IL21R, a target gene of GTF2I-the susceptibility gene for primary biliary cholangitis in Chinese Han.

AIMS: Aimed to identify a new susceptibility gene associated with primary biliary cholangitis (PBC) in Chinese Han and investigate the possible mechanism of that gene in PBC. METHODS: A total of 466 PBC and 694 healthy controls (HC) were included in our study, and genotyping GTF2I gene variants by Sequenom. CD19 + B cells were isolated for Chromatin immunoprecipitation sequencing (ChIP-seq). Additionally, MEME-ChIP was utilized to perform searches for known motifs and de novo motif discovery. The GTF2I ChIP-seq of hematopoietic cell line (K562) results were obtained from ENCODE (GSE176987, GSE177691). The Genomic HyperBrowser was used to determine overlap and hierarchal clustering between ours and ENCODE datasets. RESULTS: The frequency of the rs117026326 variant T allele was significantly higher in PBC patients than that in HC (20.26% compared with 13.89%, Pc = 1.09E-04). Furthermore, we observed an elevated proportion of GTF2I binding site located in the upstream and 5' UTR of genes in PBC in comparison with HC. Additionally, an in-depth analysis of IL21R region revealed that GTF2I might bind to the IL21R promoter to regulate the expression of the IL21R, with four peaks of GTF2I binding sites, including three increased binding sites in upstream, one increased binding site in 5' UTR. Motif analysis by MEME-ChIP uncovered five significant motifs. A significant overlap between our ChIP and GSE176987, GSE17769 were found by the Genomic HyperBroswer. CONCLUSIONS: Our study confirmed that GTF2I was associated with PBC in Chinese Han. Furthermore, our gene function analysis indicated that IL21R may be the target gene regulated by GTF2I.

RNA Sequencing of Whole Blood in Premature Coronary Artery Disease: Identification of Novel Biomarkers and Involvement of T Cell Imbalance.

Serum biomarkers were explored based on the peripheral blood gene expression profiles of premature coronary artery disease (PCAD). RNA sequencing (RNA-Seq) was used to detect PCAD-specific differentially expressed genes (DEGs). Quantitative real-time polymerase chain reaction (RT-PCR) was used to validate the most significant DEGs, and enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the effect on corresponding serum proteins. Fifty-nine PCAD-specific DEGs were identified. Functional analysis showed positive regulation of T cell-mediated cytotoxicity, regulation of T cell-mediated immunity, and the regulation of alpha-beta T cell proliferation which were enriched in PCAD. RT-PCR validated the significant difference in the expression of BAG6, MUC5B, and APOA2 between PCAD and late-onset coronary artery disease (LCAD) patients. ELISA validation showed serum MUC5B increased dramatically in PCAD when compared to LCAD. Our study found T cells contribute to the occurrence of PCAD, and the inflammatory factor MUC5B may be a novel serum marker in PCAD patients.

Animal models of primary biliary cholangitis: status and challenges.

BACKGROUND: Primary biliary cholangitis (PBC) is an autoimmune liver disease. The aetiology of PBC remains unclear, and its pathogenesis is complex. Animal models are essential to clarify the pathogenesis of PBC and explore the occurrence of early events. MAIN BODY: Herein, we review recent research progress in PBC animal models, including genetically modified, chemically inducible, biologically inducible, and protein-immunised models. Although these animal models exhibit several immunological and pathological features of PBC, they all have limitations that constrain further research and weaken their connection with clinical practice. CONCLUSION: The review will benefit efforts to understand and optimise animal models in order to further clarify PBC pathogenesis and molecular targets for therapeutic interventions.

Negative serum (1,3) -ß-D-glucan has a low power to exclude Pneumocystis jirovecii pneumonia (PJP) in HIV-uninfected patients with positive qPCR.

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.

Novel lipid biomarkers and ratios as risk predictors for premature coronary artery disease: A retrospective analysis of 2952 patients.

This study examined the associations between emerging lipid biomarkers (small dense low-density lipoprotein cholesterol [sdLDL-C), lipoprotein(a) [Lp(a)], and free fatty acids [FFA]), two ratios (sdLDL-C/LDL-C and the triglyceride-glucose [TyG) index), and the Gensini score (GS) in patients with premature coronary artery disease (PCAD) in relation to the extent of coronary stenosis. The authors evaluated a cohort of 2952 individuals undergoing coronary angiography (CAG), encompassing those with PCAD (n = 1749), late-onset coronary artery disease (LCAD; n = 328), and non-coronary artery disease (non-CAD; n = 575). Noteworthy differences were observed in the levels of the novel lipid biomarkers and ratio indexes among the PCAD, LCAD, and non-CAD groups (p < .05). Multiple logistic regression analyses pinpointed Lp(a) (OR = 2.62, 95% CI 1.22-5.63, p = .014) and the TyG index (OR = 2.53, 95% CI 1.08-5.93, p = .033) as independent risk factors for PCAD. Furthermore, these biomarkers and ratio indexes discerned substantial distinctions among PCAD patients with varying GS (p < .05). Consequently, these markers can proficiently anticipate the gravity of coronary artery stenosis (GS > 40) in PCAD patients, as evidenced by the ROC analysis. In conclusion, sdLDL-C, Lp(a), FFA, and the sdLDL-C/LDL-C and TyG indexes have considerable potential as risk and diagnostic markers for coronary artery stenosis in individuals afflicted with PCAD.

Development and validation of diagnostic and activity-assessing models for relapsing polychondritis based on laboratory parameters.

Background: Relapsing polychondritis (RP) as a rare autoimmune disease is characterized by recurrent inflammation of the organs containing cartilage. Currently, no biomarkers have been integrated into clinical practice. This study aimed to construct and evaluate models based on laboratory parameters to aid in RP diagnosis, assess activity assessment, and explore associations with the pathological process. Methods: RP patients and healthy controls (HCs) were recruited at the Peking Union Medical College Hospital from July 2017 to July 2023. Clinical data including Relapsing Polychondritis Disease Activity Index (RPDAI) score and laboratory tests were collected. Differences in laboratory data between RP patients and HCs and active and inactive patients were analyzed. Results: The discovery cohort (cohort 1) consisted of 78 RP patients and 94 HCs. A model based on monocyte counts and neutrophil to lymphocyte ratio (NLR) could effectively distinguish RP patients from HCs with an AUC of 0.845. Active RP patients exhibited increased erythrocyte sedimentation rate, complement 3, platelet to lymphocyte ratio (PLR), NLR, and C-reactive protein to albumin ratio (CAR) compared with stable patients, which were also positively correlated with RPDAI. Notably, CAR emerged as an independent risk factor of disease activity (OR = 4.422) and could identify active patients with an AUC of 0.758. To confirm the reliability and stability of the aforementioned models, a replication cohort (cohort 2) was enrolled, including 79 RP patients and 94 HCs. The monocyte-combined NLR and CAR showed a sensitivity of 0.886 and 0.577 and a specificity of 0.830 and 0.833 in RP diagnosis and activity prediction, respectively. Furthermore, lower natural killer cell levels in RP patients and higher B-cell levels in active patients may contribute to elucidating the pathological mechanisms of disease occurrence and exacerbation. Conclusions: The utilization of laboratory parameters provides cost-effective and valuable markers that can assist in RP diagnosis, identify disease activity, and elucidate pathogenic mechanisms.

SARS-CoV-2 Vaccine Uptake among Patients with Chronic Liver Disease: A Cross-Sectional Analysis in Hebei Province, China.

Chronic liver disease (CLD) patients have higher mortality and hospitalization rates after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to explore SARS-CoV-2 vaccine perceptions, side effects, factors associated with nonvaccination and attitudes toward fourth-dose vaccine among CLD patients. The differences between vaccinated and unvaccinated groups among 1491 CLD patients and the risk factors associated with nonvaccination status were analyzed. In total, 1239 CLD patients were immunized against SARS-CoV-2. CLD patients have a high level of trust in the government and clinicians and were likely to follow their recommendations for vaccination. Reasons reported for nonvaccination were mainly concerns about the vaccines affecting their ongoing treatments and the fear of adverse events. However, only 4.84% of patients reported mild side effects. Risk factors influencing nonvaccination included being older in age, having cirrhosis, receiving treatments, having no knowledge of SARS-CoV-2 vaccine considerations and not receiving doctors' positive advice on vaccination. Furthermore, 20.6% of completely vaccinated participants refused the fourth dose because they were concerned about side effects and believed that the complete vaccine was sufficiently protective. Our study proved that SARS-CoV-2 vaccines were safe for CLD patients. Our findings suggest that governments and health workers should provide more SARS-CoV-2 vaccination information and customize strategies to improve vaccination coverage and enhance vaccine protection among the CLD population.

Identification of Anti-SNRPA as a Novel Serological Biomarker for Systemic Sclerosis Diagnosis.

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.