Can CXCL13 be a prognostic marker in clear cell renal cell carcinoma?

Background: CXCL13, B-lymphocyte chemoattractant, has been associated with many diseases and cancers. One of the malignancies that CXCL13 has been investigated is clear cell renal cell carcinomas which are the most common subtype of renal cancers. Aims and Objectives: The aim of this study is to evaluate the immunohistochemical staining patterns of CXCL13 in clear cell renal cell carcinomas and to determine its relationship with pathological tumor stage, risk factors, and prognostic parameters. Materials and Methods: In this study, 99 patients who underwent partial/radical nephrectomy diagnosed with clear cell renal cell carcinoma were included. Four micron sections were taken from paraffin embedded blocks containing sufficient tumor and kidney tissue. Samples were immunohistochemically stained with CXCL13 antibody. During microscopic examination, CXCL13 positive stained cells in ten high magnification fields were counted and evaluated using a semiquantitative H score: 3 × strongly stained + 2 × moderately stained + 1 × weakly stained. The cut-off value was set as 40 for values between 0 and 300. The low and high stained groups were compared with prognostic parameters and risk factors. Statistics: The difference of continuous variables between the two groups was examined with the t test and the distribution of categorical variables with the Chi-square test. A value of P < 0.05 was considered to be statistically significant. Results: The number of lymphocytes stained with CXCL13 in the tumor was higher than in the normal kidney parenchyma (p = 0.07). Intratumoral lymphocytes were highly stained with CXCL13 in 57.5% of pT3 cases and 31.7% of pT1 cases. The amount of intratumoral lymphocytes stained with CXCL13 increased in advanced pathological stages (p = 0.05). Nonsmoking cases were mostly in the low staining group (p = 0.06). Conclusion: The relationship we found between advanced pathological stage and intratumoral CXCL13 staining in our study suggests that CXCL13 has a prognostic value in this cancer.

Use of cerebrospinal fluid CXCL13 concentration for diagnosis and monitoring of neurosyphilis: a three-case report

Introduction: Previous retrospective studies have demonstrated that the concentration of chemokine ligand CXCL13 in cerebrospinal fluid (CSF-CXCL13) is a promising biomarker in the diagnosis of neurosyphilis and, additionally, in the monitoring of therapeutic efficacy. Objective: To describe three cases of patients with neurosyphilis (NS) treated at Hospital Universitário Gaffrée e Guinle, in Rio de Janeiro, Brazil, with suspected active syphilis with neurological symptoms. Case report: Three patients from Rio de Janeiro, Brazil, were investigated for symptomatic NS. The concentration of CSF-CXCL13 was prospectively performed by enzyme-linked immunosorbent assay (ELISA) in all participants at baseline and in follow-up visits at 3 months after therapy. CSF-CXCL13 concentrations were significantly higher in all three patients with established NS. The CSF-CXCL13 concentrations decreased after 3 months of therapy compared to baseline in all cases reported. The added high concentration of CSF-CXCL13 plus CSF-TPHA reactivity above 1:40 titer agreed with the diagnosis of NS in 100% of the cases. Conclusion: In this case series, we present three cases of NS diagnosed using CXCL13 in CSF as a complementary test. These case series suggest that the clinical use of CSF-CXCL13 is useful as a supplementary biomarker for NS and for monitoring the effectiveness of NS therapy, especially in patients with nonreactive CSF-VDRL, excluding other neurologic diseases

Diagnosis Significance of the Levels of Cytokines IL-6, IL-10 and CXCL-13 in Cerebrospinal Fluid for Central Nervous System Infiltration of Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To evaluate the diagnostic value of the expression levels of cytokines interleukin-6(IL-6), interleukin-10 (IL-10) and chemokine （C-X-C motif） ligand-13 (CXCL-13) in cerebrospinal fluid (CSF) for central nervous system infiltration of lymphoma.@*METHODS@#Forty patients diagnosed as lymphoma or acute lymphoblastic leukemia in General Hospital of Northern Theater Command from July 2020 to July 2021 were collected and recorded their CSF indexes, including pressure, protein, Pandy test, nucleated cell count, glucose and chlorine content in CSF. The levels of cytokines IL-6, IL-10 and CXCL-13 were detected by Enzyme-linked immunosorbent assay.@*RESULTS@#The patients were divided into CNSI (central nervous system infiltration) group and non-CNSI group, the average levels of IL-6, IL-10, CXCL-13 and IL-10/IL-6 ratio in CNSI group were higher than those in non-CNS group, but the difference of IL-10/IL-6 ratio between the two groups was statistically significant (P<0.05). Then the patients were divided into protein elevated(n=14) group and protein normal group(n=26), the levels of IL-6 ［ (5.78±2.69) pg/ ml］ and CXCL-13 ［(0.83±0.59) pg/ml］ in protein elevated group were significantly higher than those in the protein normal group ［IL-6: (2.41±1.16) pg/ml; CXCL-13: (0.38±0.18) pg/ml］ (P<0.05). Further analysis of the expression levels of the cytokines in non-CNSI group (n=32), IL-6, IL-10, CXCL-13 level and IL-10/IL-6 ratio in the protein elevated group (n=12) were higher than those in the protein normal group (n=20), but the difference was not statistically significant.@*CONCLUSION@#The levels of IL-6, IL-10 and CXCL-13 in CSF of lymphoma patients with CNS infiltration were higher than those in non-CNS infiltration group, and those in patients with protein elevated group are higher than those in the protein normal group.

Association between circulating exhausted CD4+ T cells with poor meningococcal C conjugate vaccine antibody response in HIV-infected children and adolescents

OBJECTIVES: To investigate the expression levels of surface markers of activation (CD38 and HLA-DR), inhibition (PD-1, TIGIT and CD57) and co-stimulation (CD28 and CD127) on CD4+ T cells of children/adolescents with vertical HIV infection (HI patients) and HIV-uninfected (HU) controls vaccinated with the meningococcal C conjugate vaccine (MCC). METHODS: HI patients (n=12), aged 8-17 years, were immunized with two MCC injections, while HU controls (n=9), aged 5.3-10.7 years, received a single MCC dose (as per national recommendation at the time of this study, a single MCC vaccine dose should be given for healthy children and youth aged 1-18 years). The HI patients were categorized according to the combined antiretroviral therapy (cART) treatment. Blood samples were obtained before vaccination, after priming, and after the administration of a booster dose of vaccine to determine the serum bactericidal antibody (SBA) titers and the expression levels of surface markers on CD4+ T cells by flow cytometry. The levels of serum cytokines, IL-4 and CXCL-13 were also measured using Luminex kits. RESULTS: The co-expression of the TIGIT-HLA-DR-CD38 molecules increased in the CD4+ T cells of HI patients/no-cART who also showed a lower frequency of CD127+CD28+ CD4+ T cells than HI patients/cART and HU group subjects. There were significant negative correlations between the frequency of exhausted CD4+ T cells and the SBA response. IL-4 levels were higher in HI patients/cART and positively correlated with SBA titers but negatively associated with the expression of exhaustion markers. Moreover, the CXCL-13 levels were positively correlated with the exhausted CD4+ T cells. CONCLUSION: The results of our study suggest that the co-expression of exhaustion markers and/or loss of co-stimulatory molecules influence the SBA response in HI patients.

Increased CXCL13 and CXCR5 in Anterior Cingulate Cortex Contributes to Neuropathic Pain-Related Conditioned Place Aversion / 神经科学通报·英文版

Pain consists of sensory-discriminative and emotional-affective components. The anterior cingulate cortex (ACC) is a critical brain area in mediating the affective pain. However, the molecular mechanisms involved remain largely unknown. Our recent study indicated that C-X-C motif chemokine 13 (CXCL13) and its sole receptor CXCR5 are involved in sensory sensitization in the spinal cord after spinal nerve ligation (SNL). Whether CXCL13/CXCR5 signaling in the ACC contributes to the pathogenesis of pain-related aversion remains unknown. Here, we showed that SNL increased the CXCL13 level and CXCR5 expression in the ACC after SNL. Knockdown of CXCR5 by microinjection of Cxcr5 shRNA into the ACC did not affect SNL-induced mechanical allodynia but effectively alleviated neuropathic pain-related place avoidance behavior. Furthermore, electrophysiological recording from layer II-III neurons in the ACC showed that SNL increased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs), decreased the EPSC paired-pulse ratio, and increased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor ratio, indicating enhanced glutamatergic synaptic transmission. Finally, superfusion of CXCL13 onto ACC slices increased the frequency and amplitude of spontaneous EPSCs. Pre-injection of Cxcr5 shRNA into the ACC reduced the increase in glutamatergic synaptic transmission induced by SNL. Collectively, these results suggest that CXCL13/CXCR5 signaling in the ACC is involved in neuropathic pain-related aversion via synaptic potentiation.

Levels of CXCL13 and sICAM-1 correlate with disease activity score in patients with rheumatoid arthritis treated with tocilizumab

Abstract Background: Tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin-6 receptor, has been proven to be a safe and effective treatment for rheumatoid arthritis (RA). Because RA is a heterogenous disease and patient response to treatments can vary, identifying characteristics that predict which patients are more likely to respond to TCZ is important for optimal patient care. Serum levels of C-X-C motif chemokine ligand 13 (CXCL13) and soluble intercellular adhesion molecule-1 (sICAM-1) have been associated with response to TCZ in patients with RA. Objectives: To evaluate the association of CXCL13 and sICAM-1 with disease activity and response to TCZ in patients with early RA and those with inadequate response to disease-modifying antirheumatic drugs (DMARD-IR). Methods: Baseline and week 24 serum CXCL13 and sICAM-1 levels were measured using available patient samples from the FUNCTION (early RA) and LITHE (DMARD-IR) trials. Correlations between CXCL13 and sICAM-1 levels and Disease Activity Score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR) at baseline and between change in CXCL13 and sICAM-1 and change in DAS28-ESR at week 24 were estimated. CXCL13 and sICAM-1 changes from baseline to week 24 were compared between treatment arms. The effects of TCZ treatment and baseline DAS28-ESR, CXCL13 and sICAM-1 levels on DAS28-ESR remission and 50% improvement per the American College of Rheumatology (ACR50) response at week 24 were determined. Results: Overall, 458 patients from FUNCTION and 287 patients from LITHE were included. Correlation of baseline serum CXCL13 and sICAM-1 levels with DAS28-ESR was weak to moderate. CXCL13 and sICAM-1 levels decreased significantly at week 24 in TCZ-treated patients in both the early-RA and DMARD-IR populations. CXCL13 and sICAM-1 changes correlated moderately to weakly with DAS28-ESR changes at week 24 in both populations. The treatment regimen, but not baseline CXCL13 and sICAM-1 levels, had a significant effect on the likelihood of DAS28-ESR remission and ACR50 response. Conclusions: Although CXCL13 and sICAM-1 are modestly associated with RA disease activity, they do not predict response to TCZ in all RA populations.

Role of C-X-C motif chemokine 13 in sepsis-associated encephalopathy in mice / 中华麻醉学杂志

Objective To evaluate the role of C-X-C motif chemokine 13 (CXCL13) in sepsis-associated encephalopathy in mice.Methods A total of 64 healthy male C57BL/6J mice,aged 3-4 months,weighing 20-25 g,were divided into 4 groups (n=16 each) using a random number table method:sham operation group (Sham group),sepsis group (S group),CXCL13 siRNA group (si-CXCL13 group) and negative control siRNA group (si-control group).5-bromo-2-deoxyuridine (BrdU) 50 mg/kg was intraperitoneally injected twice a day for 3 consecutive days in the four groups,and then lipopolysaccharide 500 μg/kg was intraperitoneally injected to establish the sepsis model in S,si-CXCL13 and si-control groups.CXCL13 siRNA 5 μl and siRNA 5 μl were injected into the left lateral cerebral ventricle in si-CXCL13 and si-control groups,respectively,at 3 days before establishing the model.Morris water maze test was performed at 5 days after establishing the model.The escape latency,time spent in the target quadrant,and the number of crossing the platform were recorded.Mice were sacrificed after the end of test,brains were removed and hippocampi were isolated for examination of the pathological changes of the dentate gyrus (with a light microscope) and for determination of the expression of CXCL13,C-X-C motif chemokine receptor 5 (CXCR5) and brain-derived neurotrophic factor (BDNF),and the number of BrdU and BrdU/NeuroD positive cells (by immunofluorescence).Results Compared with sham group,the escape latency was significantly prolonged,the time spent in the target quadrant was shortened,and the number of crossing the platform was reduced on 2nd-4th days,the number of BrdU positive cells in the dentate gyrus was increased,and the number of BrdU/NeuroD positive cells in the dentate gyrus was decreased in S,siCXCL13 and si-control groups,and the expression of CXCL13 and CXCR5 was up-regulated,and the expression of BDNF was down-regulated in LPS and si-control groups (P＜0.05).Compared with S group,the escape latency was significantly shortened,the time spent in the target quadrant was prolonged,and the number of crossing the platform was increased on 2nd-4th days,the number of BrdU positive cells in the dentate gyrus was decreased,the number of BrdU/NeuroD positive cells in the dentate gyrus was increased,and the expression of CXCL13 and CXCR5 was down-regulated,and the expression of BDNF was up-regulated in si-CXCL13 group (P＜0.05),and no significant change was found in the parameters mentioned above in si-control group (P＞0.05).Conclusion CXCL13 is involved in sepsis-associated encephalopathy through regulating hippocampal neurogenesis,and the mechanism may be related to down-regulating the expression of hippocampal BDNF in mice.

Alteration in plasma chemokine profile in a high-fat diet-induced obesity mouse model / 한국영양학회지

PURPOSE: Obesity is associated with a dysregulation of metabolic balance and is regarded as a low grade chronic inflammation. Western-style diet and physical inactivity are leading causes of obesity. This study examined the profiles of forty plasma cytokines and chemokines at the same time in the early stages of high-fat diet-induced obesity using a mouse model. METHODS: A total of 30 male CD1 mice, 12 ~ 14 weeks of age, were enrolled. The mice were fed a high-fat diet for 6 weeks to induce obesity. The plasma glucose and triglyceride concentrations were measured using a hexokinase colorimetric assay kit and a serum triglyceride determination kit, respectively. The relative levels of multiple cytokines and chemokines in the plasma were determined using a mouse cytokine array kit. RESULTS: The mice exhibited significant weight gain after 6 weeks of a high-fat diet. The genital fat depot was enlarged along with an increase in the number and the mean size of white adipocytes as early as 4 weeks after a high-fat diet. In addition, the plasma glucose and triglyceride levels increased significantly after 4 weeks of a high-fat diet. Cytokine array analysis revealed a remarkable increase in the expression of both CXCL12 and CXCL13, whereas the proinflammatory cytokines remained low after 4 weeks of a high-fat diet. CONCLUSION: A significant increase in plasma levels of CXCL12 and CXCL13 was observed after 4 weeks of a high-fat diet, which might induce the migration of B lymphocytes, T lymphocytes, and monocytes from the blood to expanding adipose tissue or fat associated lymphoid clusters, playing a key role in adipose tissue remodeling and local immunity during the early stages of high-fat diet-induced obesity.

Changes of serum C-X-C motif ligand 13 concentration in senior patients undergoing total hip replacement / 临床麻醉学杂志

Objective To investigate the changes of serum C-X-C motif ligand 13 (CXCL13) concentration in senior patients undergoing total hip replacement and its role in post-operative dys-function(POCD).Methods Eighty consecutive senior patients aged 65-80 years with BMI 18.4-27.3 kg/m2,ASA physical status Ⅱ or Ⅲ,were recruited and scheduled to undergo hip joint replacement operation.Neuropsychological test was performed 1-5 d after operation and patients were divided into POCD group and non-POCD group.Serum C reactive protein (CPR),procalcitonin (PCT),IL-6, TNF-α,CXCL13 concentration were detected 1 d before and 1,2,3,4,5 d after operation. Results A total of 21 (26%)patients developed POCD 1-5 d after operation (recruited in POCD group),and the other 59 patients were recruited in non-POCD group.Compared with the time point of 1 d before operation,serum CRP,PCT,IL-6,TNF-αand CXCL13 concentration were higher 1-5 d after operation in all patients (P<0.05).The concentrationsof these factors were higher in patients from POCD group than in those from non-POCD group 1-5 d after operation (P < 0.05). Conclusion The CXCL13 concentration insenior patients undergoing total hip replacement who devel-oped POCD were higher than in those who did not developed POCD.Whether it is correlated with POCD remains further study.

Th1/Th2 cytokines and chemokine CXCL13 levels in peripheral blood and cerebrospinal fluid of patients with neurosyphilis and their clinical significance / 中华临床感染病杂志

Objective To investigate the Th1/Th2 cytokines and chemokine CXCL 13 levels in peripheral blood and cerebrospinal fluid(CSF)of patients with neurosyphilis and their clinical significance. Methods Forty seven HIV negative patients with neurosyphilis, 36 syphilis patients without neurological involvement(syphilis group)and 23 patients without infectious intracranial diseases(control group) admitted in Hangzhou Third Hospital during July 2011 to December 2014 were enrolled in the study.CSF pressure, protein contents, white blood cell counts and IgG index were detected in patients with neurosyphilis.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of Th1 cytokines (IL-2,IL-12 and IFN-γ),Th2 cytokines(IL-6,IL-10)and CXCL13 in serum and CSF in three groups.Th1/Th2 cytokines,CXCL13 levels and CSF routine were also examined in neurosyphilis patients after treatment for 3 and 12 months.ANOVA, Kruskal-Wallis test and Spearman correlation were used for data analysis.Results The levels of IL-6 and IL-10 in serum and CSF from neurosyphilis patients were higher than those in syphilis group and control group(χ2IL-6=15.43, 15.39 and 14.44, 20.01,χ2 IL-10 =16.46, 23.86 and 15.11,24.44;P<0.05 or <0.01), while the levels of IL-2, IL-12 and IFN-γin the serum and CSF were lower than those in syphilis group and control group(χ2IL-2=14.55,17.14 and 16.14,17.97;χ2IL-12=13.65,20.50 and 18.48,21.04;χ2IFN-γ=16.95,17.53 and 16.00,15.21;P<0.05 or <0.01). CXCL13 contents in CSF of neurosyphilis patients were significantly higher than those in other two groups (χ2=52.51 and 53.76, P <0.01), and were positively correlated with leucocyte counts, protein concentrations,IgG index,IL-6 and IL-10(r=0.325,0.544,0.750,0.333 and 0.382,P<0.05 or <0.01),but were negatively correlated with IL-12 levels in neurosyphilis patients(r=-0.303,P<0.05). In neurosyphilis patients,CXCL13 and IL-6 levels were reduced after treatment for 12 months(χ2=102.00 and 22.17,P<0.05 and <0.01), while the levels of IL-2 and IL-12 were increased(χ2=18.28 and 24.10,P<0.05 and <0.01).Conclusion Chemokine CXCL13 and Th1/Th2 cytokines are involved in the immune response in neurosyphilis patients, which may be used for the diagnosis and evaluation of therapeutic efficacy in patients with neurosyphilis.

The cerebrospinal fluid in multiple sclerosis: far beyond the bands / O líquido cefalorraquidiano na esclerose múltipla: muito além das bandas

ABSTRACT The cerebrospinal fluid analysis has been employed for supporting multiple sclerosis diagnosis and ruling out the differential diagnoses. The most classical findings reflect the inflammatory nature of the disease, including mild pleocytosis, mild protein increase, intrathecal synthesis of immunoglobulin G, and, most typically, the presence of oligoclonal bands. In recent years, new biomarkers have emerged in the context of multiple sclerosis. The search for new biomarkers reflect the need of a better evaluation of disease activity, disease progression, and treatment efficiency. A more refined evaluation of disease and therapy status can contribute to better therapeutic choices, particularly in escalation of therapies. This is very relevant taking into account the availability of a greater number of drugs for multiple sclerosis treatment in recent years. In this review, we critically evaluate the current literature regarding the most important cerebrospinal fluid biomarkers in multiple sclerosis. The determination of biomarkers levels, such as chemokine ligand 13, fetuin A, and mainly light neurofilament has shown promising results in the evaluation of this disease, providing information that along with clinical and neuroimaging data may contribute to better therapeutic decisions.

RESUMO A análise do líquido cefalorraquidiano tem sido empregada para avaliação diagnóstica da esclerose múltipla e a exclusão dos diagnósticos diferenciais. Os achados clássicos refletem a natureza inflamatória da doença, incluindo discreta pleocitose, leve hiperproteinorraquia, aumento da síntese intratecal de imunoglobulina G e, mais tipicamente, a presença de bandas oligoclonais. Nos últimos anos, surgiram novos biomarcadores para esclerose múltipla, e esta busca por marcadores reflete a necessidade de melhor avaliar a atividade e a progressão da doença, bem como a eficácia terapêutica. Uma avaliação mais refinada da atividade da doença e da resposta aos medicamentos pode contribuir para melhores decisões terapêuticas, particularmente no que se refere à troca de medicação. Isto é muito importante nos dias de hoje, quando surgem novas opções medicamentosas. Neste artigo de revisão, avaliamos criticamente a literatura atual referente aos novos marcadores liquóricos na esclerose múltipla. A mensuração destes marcadores, como a quimiocina CXCL13, fetuína A e, principalmente, o neurofilamento de cadeia leve, demonstrou resultados promissores na avaliação da doença, provendo informações que, em conjunto com dados clínicos e de neuroimagem, podem contribuir para melhores decisões terapêuticas.

Expression of intrahepatic chemokine CXCL13 in a mouse model of primary biliary cholangitis / 医学研究生学报

Objective The expression of chemokine C-X-C motif ligand 13 (CXCL13) within liver in primary biliary cholangitis (PBC) patients is significantly increased, but its origin and mechanism is not clear yet.The study aimed to investigate the expression of CXCL13 in the liver of mice through establishing a mouse model of PBC.Methods C57BL/6 mice were randomly divided into experiment group (n=20) control group(n=10).The mice in the experimental group were intraperitoneally injected with polyriboinosinic polyribocytidylic acid (Poly I:C) while the mice in control group were injected with PBS of the same volume.The level of serum AMA was quantified by ELISA and intrahepatic inflammatory cells were assessed by HE staining.Kupffer cells, liver sinusoidal endothelial cells, and infiltrating lymphocytes in the liver of mice were collected by in situ perfusion enzyme digestion and magnetic bead separation methods.The transcriptional level of intrahepatic CXCL13 in liver tissues and cell subpopulations were detected by qPCR.Results The serum AMA titers of the mice in experiment group increased gradually with the prolonging of modeling time and the positive rates at the 4th, 8th, and 12th week after the first injection of Poly I:C were 5.9%, 52.9% and 76.5% respectively.While the serum AMA titers of the mice in control group were at a lower level through the modeling process, with only 2 mice presenting a little higher level above positive cutoff value at the 12th week.The results of HE staining in liver tissues of both groups showed that there were a great amount of intensely infiltrating inflammatory cells in the mice of experimental group while no inflammatory cell infiltration were found in the mice of control group.The separation purity of Kupffer cells and liver sinusoidal endothelial cells in the mice of experiment group tested by flow cytometry were 76%-80%, 68%-72% respectively.Compared with the CXCL13 mRNA level in Kupffer cells [2.34(0.22-8.64)], the expression levels in liver sinusoidal endothelial cells and infiltrating lymphocytes declined[0.27(0.03-1.64), 0.05(0-0.22), P<0.05].Conclusion The chemokine CXCL13 is predominantly produced by Kupffer cells in the liver of PBC mice established by Poly I:C injection.

The expression and significance of CXCL13 in gastric mucosa of children with nodular gastritis / 临床儿科杂志

Objective To explore the expression and significance of CXCL13 in gastric mucosa of children with nodular gastritis. Methods A total of 216 pediatric patients with clinically diagnosed gastritis under gastroscopy were randomly divided into nodular group and non-nodular group according to whether there were nodular changes under endoscopy. The pathological characteristics of gastric mucosa and the expression of CXCL13/CXCR5 in gastric mucosa of all patients were evaluated. Results The infection rates of Helicobacter pylori(HP)in gastric mucosa in nodule group(n=102)and non-nodular group(n=114)were 70.59% and 42.11%, respectively; the rate of severe mononuclear cell infiltration were 74.51% and 22.81%, respectively; the proportion of neutrophil infiltration were 62.75% and 33.33%, respectively; lymph follicles occurred in 64.71% and 20.18%, respectively; and there were statistical differences between the two groups (P<0.001). Positive staining of CXCL13 and CXCR5 were found in the gastric mucosa of all HP infected patients. The percentages of positive cells of CXCL13 and CXCR5 in the gastric mucosa of the nodules group were (71.33±7.14)% and (73.54 ± 7.92)%, which were higher than those in the non-nodule group (45.88 ± 5.92)% and (50.42 ± 5.98)%, respectively, and there were statistical differences (P<0.001). Conclusions Nodular gastritis in children is mainly associated with Hp infection. The expression of CXCL13/CXCR5 is increased in gastric mucosa in children with Hp infection, especially in nodular gastritis, it may be involved in the formation of lymphoid tissue in gastric mucosa.

The mechanism of IL-17A induced the secretion of CXCL13 in gastric cancer cell line SGC-7901 / 国际检验医学杂志

Objective To study the molecular mechanism of interleukin-17A(IL-17A)induced the secretion of CXCL13 in gas-tric cancer cell line SGC-7901.Methods SGC-7901 cells were stimulated by recombination cytokine IL-17A,or SGC-7901 were pre-incubated with signal pathway inhibitor for 1 hour and then stimulated by IL-17A,the level of CXCL13 were detected by using en-zyme-linked immunosorbent assay.Results After IL-17A stimulation,the secretion of CXCL13 by SGC-7901 cells was significant-ly increased(P<0.05),which was with dose and time dependence.IL-17A-induced secretion of CXCL13 could be inhibited when SGC-7901 were pre-incubated with STAT3 inhibitor(P<0.05).However,such effect was not observed while SGC-7901 were pre-incubated with NK-κB,MEK1/2,p38/MAPK and JNK inhibitors.Conclusion IL-17A could induce the secretion of CXCL13 in gastric cancer cell line SGC-7901 by activating STAT3 signal pathway,which might play regulation role in gastric cancer.

Effect of ozone combined with arthroscopy on expression of IL1R I,CXCL13 and IL24 gene in synovium of osteoarthritis of knee joint / 实用医学杂志

Objective To observe the effect of medical ozone on the expression of IL1R,CXCL-13 and IL24 gene in synovial membrane of osteoarthritis of knee joint. Methods Sixty-five cases of knee osteoarthritis including 11 lost-cases were selected ,and randomly divided into combination group and arthroscopy group with 27 cases in each group. After arthroscopic surgery ,combination group performed intra-articular injection of 40μg/mL concentration of medical ozone 40 mL/week for 2 weeks but arthroscopic surgery group had no ozone injection. Differences of the expression of IL1R I,CXCL13 and IL24 gene and protein in synovium were compared before and after the treatment in two groups by RT-PCR and Western blot. Results Expression of IL1R I gene and protein in synovium of combination group was significantly lower than that of arthroscopy group and it showed statistical significance(P<0.01). Expression of CXCL13 gene and IL24 gene and protein in synovium of combination group was higher than those of arthroscopy group and it had statistical significance (P < 0.05). Conclusions Medical ozone can reduce the symptoms of arthritis and slow synovitis progress through influencing the expression of IL1R, CXCL-13 and IL24 gene. The effect of ozone combined with arthroscopic is better than that of simple arthroscopic debridement,but cannot stop and reverse the progression of the disease completely.

Effect of ozone combined with arthroscopy on expression of IL1R I,CXCL13 and IL24 gene in synovium of osteoarthritis of knee joint / 实用医学杂志

Objective To observe the effect of medical ozone on the expression of IL1R,CXCL-13 and IL24 gene in synovial membrane of osteoarthritis of knee joint. Methods Sixty-five cases of knee osteoarthritis including 11 lost-cases were selected ,and randomly divided into combination group and arthroscopy group with 27 cases in each group. After arthroscopic surgery ,combination group performed intra-articular injection of 40μg/mL concentration of medical ozone 40 mL/week for 2 weeks but arthroscopic surgery group had no ozone injection. Differences of the expression of IL1R I,CXCL13 and IL24 gene and protein in synovium were compared before and after the treatment in two groups by RT-PCR and Western blot. Results Expression of IL1R I gene and protein in synovium of combination group was significantly lower than that of arthroscopy group and it showed statistical significance(P<0.01). Expression of CXCL13 gene and IL24 gene and protein in synovium of combination group was higher than those of arthroscopy group and it had statistical significance (P < 0.05). Conclusions Medical ozone can reduce the symptoms of arthritis and slow synovitis progress through influencing the expression of IL1R, CXCL-13 and IL24 gene. The effect of ozone combined with arthroscopic is better than that of simple arthroscopic debridement,but cannot stop and reverse the progression of the disease completely.

Relationships between the level of chemokine CXCL13 and the distribution of Tfh subsets in peripheral blood of hepatitis B patients and their clinical significance / 中华微生物学和免疫学杂志

Objective To investigate the distribution of T follicular helper(Tfh)cell subsets in hepa-titis B patients at different immune stages and to clarify the relationships between the level of CXCL13 and the distribution of Tfh cell subsets. Methods Flow cytometry analysis was performed to detect the distribution of Tfh cells. Enzyme-linked immunosorbent assay(ELISA)was performed to measure the levels of CXCL13 in ser-um samples collected from hepatitis B patients. RT-PCR and Western blot assay were used to analyze the expres-sion of CXCL13 in HepG2 and HepG2. 2. 1. 5 cells. Results The percentages of Tfh1 cells were significantly up-regulated at the immune activation(IA)stage,while those of Tfh2 cells were significantly raised at the im-mune tolerance(IT)stage. The percentages of Tfh17 cells in patients at the stage of IT were similar to those in patients at the stage of IA,but were higher than those in responders with HBsAg seroconversion(RP)or healthy controls(HC). The expression of CXCL13 was positively correlated with the percentage of Tfh2 cells. More over,hepatitis B virus(HBV)enhanced the expression of CXCL13 at both transcriptional and translational lev-els. Conclusion HBV might up-regulate the percentage of Tfh2 cells through promoting the expression of CXCL13,which resulted in the induction of immune tolerance. Elucidating the functions of Tfh1,Tfh2 and Tfh17 cells and understanding the type conversion mechanism among the three subsets are important for further researches on HBV-induced immunosuppression.

Comparison of diagnostic values of Clusterin, CXCL13, Podoplanin, CD21 and CD35 in foll-cular dendritic cell sarcoma / 临床与实验病理学杂志

Purpose To evaluate the diagnostic values of Clusterin, CXCL13, Podoplanin (D2-40), CD21 and CD35 in follcular den-dritic cell sarcoma. Methods The expression levels of 10 cases of follcular dendritic cell sarcoma ( FDCS) and 12 types of FDCS mimics (83 cases in total) were investigated by immunohistochemical methods, the latter including solitary fibrous tumor, leiomyosar-coma, gastrointestinal stromal tumor and others. The diagnostic validities of the five biomarkers were compared. Results ( 1 ) The positive rates of Clusterin, CXCL13, D2-40, CD21 and CD35 in the FDCS group were 100%, 70%, 60%, 90% and 80%, respec-tively, the corresponding rates in the control group were 30%, 4%, 11%, 2% and 0 in turn. (2) The five biomarkers could be cate-gorized into 3 groups, according to their diagnostic values in FDCS. The first group included CD21 and CD35, which had much higher sensitivities (90%, 80%), specificities (100%, 98%) and accuracies (98%, 96%), compared with the other biomarkers. The second group included CXCL13 and D2-40, which had a relatively lower sensitivities (70%, 60%), specificities (96%, 89%) and accuracies (94%, 86%), compared with CD21 and CD35. The third group included Clusterin, which had the highest sensitivity (100%), while the specificity (70%)and accuracy (73%) were inferior to the first and second groups. (3) The diagnostic values of CD21 and CD35 combination were 100%, 98%, 98%, 83% and 100%, respectively. Conclusions (1) CD21 and CD35 are the most valuable biomarkers for FDCS. The combined diagnostic effect of the two markers is generally superior to that of single marker. (2) Clusterin has the highest sensitivity for FDCS. However, the frequent expression in FDCS mimickers restricts its diagnostic values for FDCS. (3) CXCL13 and D2-40 may be used as a marker for FDCS, but are not recommended as the first selection based on their diagnostic performance. (4) On the reasons that FDCS mimickers may not uncommonly express Clusterin and D2-40, and rarely show positivity for CD21 or CXCL13, more attention should be paid to the phenomenon to avoid misdiagnosis.

Hypoxia inducible transcription factor (HIF-1) regulates CXCL13 expression: Clinical implications in pediatric non-Hodgkin's lymphoma

Background: Lymphomas are B and/or T cell clonal neoplasms in various states of differentiation, characteristically compromising lymph nodes. They are constituted by B and T lymphocytes that reach the node by chemokine-mediated recruitment including CXCL13. Hypoxia-inducible transcription factor (HIF-1α) plays a role in cellular adaptation to oxygen concentration changes. It also regulates expression of chemokines such as CXCL12, CCL20, and CCL5 as well as some of their receptors such as CCR7 and CXCR4. Methods: We performed in silico analysis of the CXCL13 promoter, pharmacologic modulation of HIF-1α activity and, using reporter plasmids, site-directed mutation and DNA-protein interaction analysis we analyzed the relation between HIF-1α activity and CXCL13 expression. Moreover, we did tissue microarray and immunohistochemistry to see the expression of HIF-1α and CXCL13. Results: This study detected three possible HIF-1α binding sites suggesting that this chemokine may be regulated by the CXCL13 transcription factor. We showed that CXCL13 expression is directly dependent, whereby an increase in HIF-1α activity increases CXCL13 expression and decreased HIF-1α activity in turn decreases CXCL13 expression. We proved that HIF-1α transcriptionally regulates the expression of CXCL13 in a direct manner. We established that HIF-1α and CXCL13 are greatly overexpressed in the most aggressive pediatric lymphomas. Conclusions: For the first time, this study showed that HIF-1α directly regulates transcriptional CXCL13 and that both proteins are overexpressed in the most aggressive forms of pediatric lymphoma. This suggests that they may play a significant role in the pathogenesis of pediatric non-Hodgkin's lymphoma.

The role and clinical significance of follicular helper T cells and interleukin-21, CXCL13 in patients with ankylosing spondylitis / 中华风湿病学杂志

Objective To test the level of follicular helper T cells (Tfh) and interleukin (IL)-21,CXCL13 in the peripheral blood of patients with ankylosing spondylitis (AS),and to analyze the relationship between Tfh and clinic features and explore the possible immunological pathogenesis of AS.Methods The Tfh cells were obtained from patients and normal controls and detected by flow cytometry.While the levels of IL-21,CXCL13 in patients and normal controls were measured by enzyme-linked immunosorbent assay (ELISA) tests.Data analysis were performed by Student's t-test,Rank-sum test,Spearman's correlation test.Results The expression of CD4+CXCR5 qCOS + cells (Tfh) (mean rank 33.71) and IL-21 [(299±27) ng/L],CXCL13 [(5.8±1.0) μg/L] in the peripheral blood of AS was significantly higher than normal controls [mean rank 23.54,(176±26) ng/L,(4.2±0.8) μg/L] (Z=-2.258,t=17.221,t=6.464,all P＜0.05).It was similar in AS with peripheral joint involvement compared with AS of non-peripheral joint involvement,and there was no difference between AS patients with positive HLA-B27 and those without HLA-B27.Mean -while,no correlation was found between the expression of Tfh,IL-21,CXCL13 and level of ESR,CRP,BASDAI.And there was no significant correlation between the expression of Tfh and IL-21,CXCL13 (P＞0.05).Conclusion The expression of Tfh and the levels of IL-21,CXCL13 are increased significantly,but are not closely relatedto disease activity.These results indicate that the abnormality of Tfh may play an important role in the pathogenesis of AS.