Blood and CSF findings of cellular immunity in anti-NMDAR encephalitis.

OBJECTIVES: To investigate the immunopathogenic mechanisms of anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) by characterizing the changes of immune cells in both peripheral blood (PB) and cerebrospinal fluid (CSF) of patients with NMDAR-E. METHODS: Cytology and flow cytometry were used to explore and compare different immunological parameters in PB and CSF of patients with NMDAR-E, viral encephalitis (VE) and healthy volunteers. Moreover, different models were established to assess the possibility of identifying NMDAR-E patients based on PB and CSF parameters. RESULTS: The neutrophil counts and monocyte-to-lymphocyte ratios (MLR) in PB are higher in NMDAR-E patients than in both VEs and controls (P < 0.001, respectively), while the percentages of CD3 + T, CD4 + T lymphocytes, and the leukocytes count in CSF were lower in NMDAR-Es than in VEs (P < 0.01, respectively). The higher percentages of CD8 + T cells in blood and CSF were both correlated with more severe NMDAR-E (P < 0.05, respectively). The poor neurological status group had significantly higher PB leukocytes but lower CSF leukocyte count (P < 0.05). Longitudinal observations in patients with NMDAR-E showed a decreasing trend of leukocyte count, neutrophils count, neutrophil-to-monocyte ratios (NMR), and neutrophil-to-lymphocyte ratios (NLR) with the gradual recovery of neurological function. CONCLUSIONS: The expression patterns of T lymphocyte subsets were different in patients with NMDAR-E and viral encephalitis. The changing trends of leukocyte and lymphocyte populations in peripheral blood and cerebrospinal fluid may provide clues for the diagnosis of different types of encephalitides, including NMDARE, and can be used as immunological markers to assess and predict the prognosis.

Acute exacerbation of idiopathic pulmonary fibrosis disease: a diagnosis model in China.

OBJECTIVE: To develop and validate a diagnosis model to inform risk stratified decisions for idiopathic pulmonary fibrosis patients experiencing acute exacerbations (AE-IPF). METHODS: In this retrospective cohort study performed from 1 January 2016 to 31 December 2022, we used data from the West China Hospital of Sichuan University for model development and validation. Blood test results and the underlying diseases of patients were collected through the HIS system and LIS system. An algorithm for filtering candidate variables based on least absolute shrinkage and selection operator (LASSO) regression. Logistic regression was performed to develop the risk model. Multiple imputation handled missing predictor data. Model performance was assessed through calibration and diagnostic odds ratio. RESULTS: 311 and 133 participants were included in the development and validation cohorts, respectively. 3 candidate predictors (29 parameters) were included. A logistic regression analysis revealed that dyspnea, percentage of CD4+ T-lymphocytes, and percentage of monocytes are independent risk factors for AE-IPF. Nomographic model was constructed using these independent risk factors, and the C-index was 0.69. For internal validation, the C-index was 0.69, and that indicated good accuracy. Diagnostic odds ratio was 5.40. Meanwhile, in mild, moderate, and severe subgroups, AE positivity rates were 0.37, 0.47, and 0.81, respectively. The diagnostic model can classify patients with AE-IPF into different risk classes based on dyspnea, percentage of CD4+ T-lymphocytes, and percentage of monocytes. CONCLUSION: A diagnosis model was developed and validated that used information collected from HIS system and LIS system and may be used to risk stratify idiopathic pulmonary fibrosis patients experiencing acute exacerbations.

Photocatalytic C-N bond construction toward high-value nitrogenous chemicals.

The construction of carbon-nitrogen bonds is vital for producing versatile nitrogenous compounds for the chemical and pharmaceutical industries. Among developed synthetic approaches to nitrogenous chemicals, photocatalysis is particularly prominent and has become one of the emerging fields due to its unique advantages of eco-sustainable characteristics, efficient process integration, no need for high-pressure H2, and tunable synthesis methods for developing advanced photocatalytic materials. Here, the review focuses on potential photocatalytic protocols developed for the construction of robust carbon-nitrogen bonds in discrepant activation environments to produce high-value nitrogenous chemicals. The photocatalytic C-N bond construction strategies and involved reaction mechanisms are elucidated.

ASMT determines gut microbiota and increases neurobehavioral adaptability to exercise in female mice.

N-acetylserotonin O-methyltransferase (ASMT) is responsible for melatonin biosynthesis. The Asmt gene is located on the X chromosome, and its genetic polymorphism is associated with depression in humans. However, the underlying mechanism remains unclear. Here, we use CRISPR/Cas9 to delete 20 bp of exon 2 of Asmt, and construct C57BL/6J mouse strain with Asmt frameshift mutation (Asmtft/ft). We show that female Asmtft/ft mice exhibit anxiety- and depression-like behaviors, accompanied by an obvious structural remodeling of gut microbiota. These behavioral abnormalities are not observed in male. Moreover, female Asmtft/ft mice show a lower neurobehavioral adaptability to exercise, while wild-type shows a "higher resilience". Cross-sectional and longitudinal analysis indicates that the structure of gut microbiota in Asmtft/ft mice is less affected by exercise. These results suggests that Asmt maintains the plasticity of gut microbiota in female, thereby enhancing the neurobehavioral adaptability to exercise.

Clinical Performance of the Line Immunoassay, Digital Liquid Chip Method, and Chemiluminescent Immunoassay for Detecting Specific Antinuclear Antibodies.

CONTEXT.­: Antinuclear antibodies (ANAs) against certain antigens are useful for identifying autoimmune disorders. Although new solid phase-based immunoassays have been developed for evaluating ANAs, the conventional line immunoassay (LIA) is commonly used in clinical practice. OBJECTIVE.­: To compare the clinical performance of 2 newly developed methods for detecting specific ANAs with LIA. DESIGN.­: Six hundred ninety-six serum samples were collected from 559 patients with autoimmune disease (AID) and 137 controls. The samples were screened by using the LIA, digital liquid chip method (DLCM), and chemiluminescent immunoassay (CLIA) for specific ANAs. The agreement across assays and the clinical performance of each assay in diagnosing ANA-associated rheumatic diseases (AARDs) were evaluated. RESULTS.­: Perfect agreement was observed among all assays for anti-centromere protein B (κ = 0.85-0.97), anti-ribosome P (κ = 0.85-0.88), anti-SSA 52 (κ = 0.86-0.89), and anti-SSA 60 (κ = 0.89-0.91); moderate to substantial agreement was detected for the autoantibodies against Sm, Jo-1, ribonucleoprotein, Scl-70, and SSB (κ = 0.55-0.80). LIA exhibited better sensitivity for diagnosing AARDs, while DLCM and CLIA demonstrated higher specificity. In the subset of AIDs, especially systemic lupus erythematosus, antibody positive percentages varied greatly between assays. CONCLUSIONS.­: The 3 assays showed comparable qualitative agreement; however, the standardization of testing for ANAs remains challenging owing to intermanufacturer variations. Moreover, DLCM and CLIA exhibited better specificity in distinguishing non-AID individuals, whereas LIA was more sensitive in diagnosing AARDs.

Localization of multiple DNAzymes as a branchedzyme-powered nanodevice for the immunoassay of tumor biomarkers.

Traditional immunoassay methods often face challenges due to the labeling procedure of protein enzymes, the use of multiple antibodies, and severe conditions. To address these limitations, we propose the concept of incorporating branchedzyme-powered nanodevices into immunoassays. In this strategy, multiple DNAzymes are localized onto gold nanoparticles (AuNPs) along with substrates. The localization format facilitates intramolecular reactions between DNAzymes and substrates, leading to accelerated kinetics of the nanodevice. Upon the formation of an immunocomplex with an antibody on a 96-well plate, the branchedzyme-powered nanodevice catalytically releases multiple fluorescent signals under ambient temperature, eliminating the need for secondary antibodies. The branched DNAzymes exhibit catalytic properties similar to those of protein enzymes, thus simplifying the assay procedure and achieving isothermal detection. Furthermore, the detection process can be controlled by the addition or deletion of cofactors. Additionally, the affinity ligand can be easily modified to construct nanodevices specific to different targets without requiring extensive redesign. This strategy has demonstrated successful quantification of tumor biomarkers such as alpha-fetoprotein (AFP) and prostate-specific antigen (PSA) at subpicomolar concentrations, showcasing its suitability for clinical applications. Consequently, the branchedzyme-powered nanodevice represents a valuable addition to the immunoassay toolbox, opening new possibilities for clinical diagnostics.

Differential expression and correlation of immunoregulation related piRNA in rheumatoid arthritis.

Background: Although PIWI-interacting RNAs (piRNAs) have recently been associated with germline development and many human diseases, their expression pattern and relationship in autoimmune diseases remain indistinct. This study aimed to investigate the presence and correlation of piRNAs in rheumatoid arthritis (RA). Methods: We first analyzed the expression profile of piRNAs using small RNA sequencing in peripheral leukocytes of three new-onset untreated RA patients and three healthy controls (HCs). We then selected piRNAs related to immunoregulation by bioinformatics analysis and verified them in 42 new-onset RA patients and 81 HCs by RT-qPCR. Furthermore, a receiver operating characteristic curve was generated to quantify the diagnostic performance of these piRNAs. A correlation analysis was conducted to observe the link between piRNA expression and RA clinical characteristics. Results: A total of 15 upregulated and 9 downregulated piRNAs among 1,565 known piRNAs were identified in peripheral leukocytes of RA patients. Dysregulated piRNAs were enriched in numerous pathways related to immunity. After selection and validation, two immunoregulation piRNAs (piR-hsa-27620 and piR-hsa-27124) were significantly elevated in RA patients and have good abilities to distinguish patients from controls, which have the potential to serve as biomarkers. PIWI and other proteins implicated in the piRNA pathway were also associated with RA.

Gut microbiota in pre-clinical rheumatoid arthritis: From pathogenesis to preventing progression.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive polyarthritis that leads to cartilage and bone damage. Pre-clinical RA is a prolonged state before clinical arthritis and RA develop, in which autoantibodies (antibodies against citrullinated proteins, rheumatoid factors) can be present due to the breakdown of immunologic self-tolerance. As early treatment initiation before the onset of polyarthritis may achieve sustained remission, optimize clinical outcomes, and even prevent RA progression, the pre-clinical RA stage is showing the prospect to be the window of opportunity for RA treatment. Growing evidence has shown the role of the gut microbiota in inducing systemic inflammation and polyarthritis via multiple mechanisms, which may involve molecular mimicry, impaired intestinal barrier function, gut microbiota-derived metabolites mediated immune regulation, modulation of the gut microbiota's effect on immune cells, intestinal epithelial cells autophagy, and the interaction between the microbiome and human leukocyte antigen alleles as well as microRNAs. Since gut microbiota alterations in pre-clinical RA have been reported, potential therapies for modifying the gut microbiota in pre-clinical RA, including natural products, antibiotic therapy, fecal microbiota transplantation, probiotics, microRNAs therapy, vitamin D supplementation, autophagy inducer-based treatment, prebiotics, and diet, holds great promise for the successful treatment and even prevention of RA via altering ongoing inflammation. In this review, we summarized current studies that include pathogenesis of gut microbiota in RA progression and promising therapeutic strategies to provide novel ideas for the management of pre-clinical RA and possibly preventing arthritis progression.

Sugar-sweetened beverage consumption retarded weight gain but not induced depression and anxiety-like behaviors in mice.

AIMS: To assess the effects of sugar-sweetened beverage (SSB) consumption and exercise on behaviors. METHODS: Twenty-four male mice were divided into four groups: the water + sedentary (WS), the SSB + sedentary (CS), the water + exercise (WE), and the SSB + exercise (CE). After three-month of interventions, forced swim test (FST), open field test (OFT), and morris water maze (MWM) were conducted. Then, mRNA levels of MAO-A, COMT, and 5-HT1A and protein levels of synapsin, STAT3, A2AR, CRTC1, CREB, and BDNF were measured. RESULTS: Under a similar baseline body weight condition, SSB consumption reduced the weight gain from the 3rd week (p < 0.05, or p < 0.01). Exercise decreased the escape latency in the CE group when compared to the CS group on day5 (p < 0.01) and increased the time in the target quadrant in the WE group than the WS group on day4 (p < 0.05) and 5 (p < 0.01) during MWM. No significant differences were found during the FST and OFT. COMT mRNA level was increased after SSB consumption (p < 0.05), but no differences were found in the MAO-A and 5-HT1A mRNA levels and the concerned biomarkers, all of which were previously reported to be associated with depression and anxiety-like behaviors. CONCLUSION: SSB consumption reduced weight gain but not result in depression and anxiety-like behaviors in mice. Therefore, the behavioral effects of exercise were not significant. This is not consistent with the results of previous epidemiological surveys of humans.

Photothermal technique-enabled ambient production of microalgae biodiesel: Mechanism and life cycle assessment.

Thermocatalytic (trans)esterification of oils/lipids to produce biodiesel is generally energy-consuming, reversible, and controlled by the equilibrium law. Herein, a light-induced photothermal process was illustrated to be highly efficient for biodiesel production (96.8 % yield) from microalgae lipids at room temperature enabled by a biomass-based SO3H-functionalized graphene-like heterogeneous catalyst (S-NGL-600), as optimized by response surface methodology. Infrared thermal imaging indicated that interfacial solar heating led to forming a local photothermal catalytic system, reaching 72.2 °C in 2 min. The local light heating was conducive to evaporation and removal of water from acid sites, resulting in local excess of microalgae lipids to facilitate the forward reaction. Notably, the photothermal catalyst was highly recyclable and exhibited a significantly higher conversion rate of microalgae lipids than industrially used catalyst H2SO4. Life cycle assessment suggested energy-saving advantage (0.87 MJ/MJ) and environmental protection (-89.42 CO2eq/MJ) of the photothermal-driven protocol for microalgae biodiesel production.

Association of Gene Polymorphisms in CXC Chemokine Receptor 5 with Rheumatoid Arthritis Susceptibility.

Rheumatoid arthritis (RA) is caused by complicated interactions between genes and the environment. CXC chemokine receptor 5 (CXCR5) is required for B and T follicular helper cell migration and humoral immunity generation. Therefore, this study aimed to assess whether polymorphisms of the CXCR5 gene are implicated in RA development and progression. This case-control study enrolled 285 RA patients and 291 healthy controls. The polymerase chain reaction-ligase detection reaction method was used to genotype rs630923, rs497916, rs3922, and rs676925 in the CXCR5 gene. Epidemiological, clinical, and laboratory data were collected retrospectively. The rs630923 A allele was associated with a higher risk of RA (AOR [adjusted odds ratio]=2.00, 95% confidence interval [CI] =1.14-3.53). However, in the RA group, the frequency of the rs497916 T allele was lower (AOR=0.69, 95% CI=0.51-0.93). Regarding rs3922, AG+GG genotype carriers were at a significantly lower risk for RA than AA genotype carriers (AOR=0.70, 95% CI=0.49-0.99). In the RA group, we found that the different genotypes were significantly associated with specific laboratory values, including rheumatoid factor, total bilirubin, total cholesterol, low-density lipoprotein cholesterol, and alkaline phosphatase. This is the first report indicating that CXCR5 polymorphisms were associated with RA susceptibility. These findings lead to a rising possibility of identifying RA-susceptible individuals based on genetic markers.

Codon-optimized FAM132b gene therapy prevents dietary obesity by blockading adrenergic response and insulin action.

BACKGROUND: FAM132b (myonectin) has been identified as a muscle-derived myokine with exercise and has hormone activity in circulation to regulate iron homeostasis and lipid metabolism via unknown receptors. Here, we aim to explore the potential of adeno-associated virus to deliver FAM132b in vivo to develop a gene therapy against obesity. METHODS: Adeno-associated virus AAV9 were engineered to induce overexpression of FAM132b with two mutations, A136T and P159A. Then, AAV9 was delivered into high-fat diet mice through tail vein, and glucose homeostasis and obesity development of mice were observed. Methods of structural biology were used to predict the action site or receptor of the FAM132b mutant. RESULTS: Treatment of high-fat diet-fed mice with AAV9 improved glucose intolerance and insulin resistance, and resulted in reductions in body weight, fat depot, and adipocyte size. Codon-optimized FAM132b (coFAM132b) reduced the glycemic response to epinephrine (EPI) in the whole body and increased the lipolytic response to EPI in adipose tissues. However, FAM132b knockdown by shRNA significantly increased the glycemic response to EPI in vivo and reduced adipocyte response to EPI and adipose tissue browning. Structural analysis predicted that the FAM132b mutant with A136T and P159A may form a weak bond with ß2 adrenergic receptor (ADRB2) and may have more affinity for insulin and insulin-receptor complexes. CONCLUSIONS: Our study underscores the potential of FAM132b gene therapy with codon optimization to treat obesity by modulating the adrenergic response and insulin action. Both structural biological analysis and in vivo experiments suggest that the adrenergic response and insulin action are most likely blockaded by FAM132b mutants.

Gene expression profile associated with Asmt knockout-induced depression-like behaviors and exercise effects in mouse hypothalamus.

Sleep disorder caused by abnormal circadian rhythm is one of the main symptoms and risk factors of depression. As a known hormone regulating circadian rhythms, melatonin (MT) is also namely N-acetyl-5-methoxytryptamine. N-acetylserotonin methyltransferase (Asmt) is the key rate-limiting enzyme of MT synthesis and has been reportedly associated with depression. Although 50-90% of patients with depression have sleep disorders, there are no effective treatment ways in the clinic. Exercise can regulate circadian rhythm and play an important role in depression treatment. In the present study, we showed that Asmt knockout induced depression-like behaviors, which were ameliorated by swimming exercise. Moreover, swimming exercise increased serum levels of MT and 5-hydroxytryptamine (5-HT) in Asmt knockout mice. In addition, the microarray data identified 10 differentially expressed genes (DEGs) in KO mice compared with WT mice and 29 DEGs in KO mice after swimming exercise. Among the DEGs, the direction and magnitude of change in epidermal growth factor receptor pathway substrate 8-like 1 (Eps8l1) and phospholipase C-ß 2 (Plcb2) were confirmed by qRT-PCR partly. Subsequent bioinformatic analysis showed that these DEGs were enriched significantly in the p53 signaling pathway, long-term depression and estrogen signaling pathway. In the protein-protein interaction (PPI) networks, membrane palmitoylated protein 1 (Mpp1) and p53-induced death domain protein 1 (Pidd1) were hub genes to participate in the pathological mechanisms of depression and exercise intervention. These findings may provide new targets for the treatment of depression.

Detection of IgA Antiphospholipid Antibodies Does not Improve Thrombotic Antiphospholipid Syndrome Classification: A two-Center Study.

BACKGROUND: Thrombotic antiphospholipid syndrome (APS) is a systemic autoimmune disease; its diagnosis requires meeting both clinical and laboratory criteria. Prevalence rates of immunoglobulin (Ig) A anticardiolipin antibodies (aCL) and IgA anti-ß2 glycoprotein I antibodies (aß2GPI) remain unknown, and the clinical value of these antibodies to APS classification remains controversial. Therefore, we aimed to examine both items in the Chinese population. METHODS: Using chemiluminescence immunoassay, antiphospholipid antibodies (aPL) were quantified in 12,582 hospital-based general population, 278 thrombotic APS patients, and 233 healthy controls. RESULTS: In the general population, the positive rates of IgA aCL and IgA aß2GPI antibodies were 2.87% and 1.99%, respectively. Furthermore, isolated IgA aPL-positivity rate was 0.72% in patients with APS, which was comparable to those in the general population (0.68%, p = 1) and in healthy controls (0.43%, p = 1). Among the IgA aPL-positive individuals in the general population, isolated IgA-positive individuals had lower serum levels of IgA antibodies (p = 0.007 for IgA aCL and p = 0.059 for IgA aß2GPI). Regarding to APS classification, adding IgA aPL into conventional aPL assays may not improve and may even deteriorate the net reclassification index for APS; besides, no association between thrombosis and IgA aPL was observed. CONCLUSIONS: this study assessed the prevalence of various aPL in Chinese population. IgA aPL may not enhance the classification ability of established laboratory criteria for thrombotic APS. Our data do not support the addition of IgA aPL to conventional aPL assays.

Association of genetic polymorphisms in IL-23R and IL-17A with the susceptibility to IgA nephropathy in a Chinese Han population.

IgA Nephropathy (IgAN) is one of the most common causes of chronic kidney damage worldwide. Identifying new genetic factors associated with IgAN risk is of invaluable importance. To explore the association between polymorphisms of IL-23R and IL-17A and the susceptibility of IgAN, 164 IgAN patients and 192 healthy controls were genotyped for five SNPs in a Chinese Han population. A comparative analysis between genotype distributions, clinical indexes and pathological grades in the IgAN patients was also performed. The GG genotype and a G allele of rs7517847 were associated with a decreased IgAN risk (OR: 0.545; 95% CI: 0.299-0.993; p = 0.046; OR: 0.730; 95% CI: 0.541-0.984; p = 0.039) compared to the TT genotype and T allele respectively. Furthermore, the AA genotype of rs2275913 appeared to reduce the IgAN risk (OR: 0.405; 95% CI: 0.209-0.786; p = 0.007) compared to the GG genotype. Consistently, individuals harboring an AA genotype had a lower IgAN risk (OR: 0.380; 95% CI: 0.211-0.686; p = 0.001) under the recessive model. Our study demonstrated for the first time the significant associations of rs7517847 in IL-23R and rs2275913 in IL-17A with the risk of IgAN in Chinese Han.

Dense fine speckled immunofluorescence pattern in a Chinese population: Prevalence and clinical association.

OBJECTIVE: To provide information on the prevalence and possible clinical association in a Chinese population for medical practice of the dense fine speckled pattern (DFS pattern). METHODS: A retrospective study was conducted with patients who had the DFS pattern from June 2018 to December 2019 in West China Hospital. RESULTS: A total of 469 patients (1.27% of patients with positive anti-nuclear antibody indirect immunofluorescence (ANA IIF) test results) revealed the DFS pattern, of which 92.96% had isolated DFS pattern and 23.67% had titers above/equal to 1:320. The average age of patients with the DFS pattern was 43.45 years, and females accounted for 76.97% of them. Ten different kinds of diseases made up the vast majority of the disease spectrum, in which inflammatory or infectious diseases (46.11%), mental diseases (21.45%), and systemic autoimmune rheumatic diseases (SARDs) (18.23%) ranked in the top three. The most common SARDs were rheumatoid arthritis (RA), undifferentiated connective tissue disease (UCTD), and systemic lupus erythematosus (SLE). Forty-six patients (10.55%) had positive or suspicious extractable nuclear antigen (ENA) antibodies test results and a higher risk of suffering from SARDs. Forty-seven patients would be missed if the DFS pattern with negative ENA antibodies test result was considered as exclusion criterion of SARDs. CONCLUSIONS: The DFS pattern is basically isolated and with low titer. It is unwise to exclude the diagnosis of SARDs only depending on the appearance of the DFS pattern. Autoimmune diseases-related antibodies, clinical information of patients, and long-term follow-up are of great importance to avoid missed or delayed diagnosis of SARDs.

Analysis of inflammation-related microRNA expression in patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a complex genetic disease characterized by axial skeletal inflammation. Available scientific evidence suggests that a relationship may exist between miRNA expression levels and the pathogenesis of AS. This study investigated the clinical diagnostic value of miR-146a, miR-15a, miR-20a, miR-125a-3p, miR-125a-5p, miR-125b-5p, miR-148a, miR-149a, miR-499, and miR-155a in AS. A total of 44 AS patients and 56 healthy controls (HCs) were included in the study. MiRNA expression levels were detected using fluorescence quantitative PCR (qPCR). Results showed that the expression levels of miR-146a, miR-125a-3p, miR-125a-5p, miR-125b-5p, and miR-155a decreased, whereas miR-499a expression increased significantly in AS patients compared to that in the controls. Logistic regression analysis with receiver operating characteristic (ROC) curves showed that combined miR-146a/miR-125a-5p/miR-125b-5p/miR-499a/miR-155a (area under curve [AUC] = 0.824, 95% confidence interval [CI] = 0.727-0.921) had high sensitivity and specificity for AS diagnosis. C-reactive protein (CRP) levels were positively correlated with the expression of miR-125a-5p (rs = 0.438, p = 0.005) and miR-155a (rs = 0.414, p = 0.006), which indicates that miR-125a-5p and miR-155a can perhaps aggravate AS-induced inflammation. Our findings suggest the association of miR-125a-5p and miR-155a with disease activity in AS patients. Furthermore, miR-146a, miR-125a-5p, miR-125b-5p, miR-499a, and miR-155a could have potential diagnostic value in AS.

Anti-Golgi Antibody as a Potential Indicator for Rheumatoid Arthritis.

OBJECTIVE: To reveal the relationship between anti-Golgi antibody (AGA) and clinical diseases through retrospective analysis. METHODS: The clinical data of 584 cases testing positive for AGA in the past 11 years were collected and retrospectively analyzed. RESULTS: AGA pattern accounted for .2% of positive ANA results. In total, 35.0% of diagnosed patients had autoimmune diseases (AID), mainly rheumatoid arthritis (RA). High-titer AGA (≧1:1000) was common in AID. In nondiagnosed patients with clinical symptoms, joint pain/muscle pain was the most common. CONCLUSIONS: Positive AGA with high titer was closely related to RA. Joint pain/muscle pain was the most common symptom in patients who tested AGA positive. Therefore, AGA may be a key indicator of RA in the Chinese population.

ETS1 polymorphism rs73013527 in relation to serum RANKL levels among patients with RA.

ABSTRACT: We previously identified E26 transformation specific sequence 1 (ETS1) rs73013527 single nucleotide polymorphism associated with RA susceptibility and disease activity. In the present study, we aims to further investigate the association between ETS1 rs73013527 and receptor activator of nuclear factor kappa B ligand (RANKL), an index related to bone destruction and was reported to elevate in RA.We determined genotypes of ETS1 rs73013527, serum RANKL concentration, clinical characteristics (disease duration, disease activity score for 28 painful/swollen joints), and laboratory markers (rheumatoid factor, anti-citrullinated protein antibody, anti-keratin antibody, c-reactive protein, erythrocyte sedimentation rate) of 254 RA cases. Univariate and multivariate analysis were employed to explore the association between ETS1 rs73013527 and serum RANKL levels in RA patients.Univariate and multivariate analysis indicated no association of serum RANKL levels with patient age, gender, clinical characteristics, and laboratory markers. Univariate analysis, not multivariate analysis indicated genotype CT/TT of ETS1 rs73013527 was significantly associated with elevated RANKL levels in RA patients.ETS1 rs73013527 is in relation to serum RANKL levels among patients with RA. ETS1 probably might be an indirect factors involved in RANKL regulation in RA.

IKZF1 polymorphisms are associated with susceptibility, cytokine levels, and clinical features in systemic lupus erythematosus.

Ikaros family zinc finger 1(IKZF1) encodes a lymphoid-restricted zinc finger transcription factor named Ikaros that regulates lymphocyte differentiation and proliferation as well as self-tolerance. Increasing evidence indicates that IKZF1 could contribute to the pathogenesis of autoimmune diseases. Recent research has provided evidence that IKZF1 might correlate with Systemic lupus erythematosus (SLE), but no clear definition has been made yet. In this study, we focus on the relationship between IKZF1 polymorphisms and SLE susceptibility, cytokine levels, and clinical characteristics in the Chinese Han population.One thousand seventy-six subjects, including 400 SLE patients and 676 healthy controls, were included in this study. Three single nucleotide polymorphisms within IKZF1 containing rs4917014, rs11980379, and rs4132601 were genotyped in all subjects by an improved multiplex ligation detection reaction technique. 143 subjects from SLE patients were randomly selected for testing the levels of serum cytokines. The clinical characteristics of SLE patients were gathered and collated from medical records. The data were analyzed mainly using SPSS20.0 (SPSS lnc., Chicago, IL).Significant relationships were observed between rs4132601 and SLE susceptibility, CD40 ligand, and malar rash (P < .001, P = .04, and P = .01, respectively). In addition, significant relationships were observed between rs4917014 and susceptibility, granzyme B level, and hematological disorder in SLE (P = .005, P = .03 and P = .005, respectively).The results further support that IKZF1 may have an important role in the development and pathogenesis of SLE. Allele G of rs4132601 and rs4917014 is related to a decreased risk of SLE occurrence and associated with clinical features in SLE patients, including CD40 ligand level, granzyme B level, malar rash, and hematological disorder, which play important roles in disease progression.