Background: Renal osteodystrophy (ROD) is a bone disorder resulting from chronic kidney disease (CKD) and related metabolic diseases. Dickkopf-related protein-1 (DKK-1) is critical in regulating bone biology. This stu...Background: Renal osteodystrophy (ROD) is a bone disorder resulting from chronic kidney disease (CKD) and related metabolic diseases. Dickkopf-related protein-1 (DKK-1) is critical in regulating bone biology. This study aimed to evaluate the serum DKK-1 level as a bone marker in children with CKD who undergo regular hemodialysis (HD). Subjects and Methods: This case-control study involved 40 children with CKD on HD and 40 healthy children as controls. The study measured serum DKK-1 levels and performed a dual-energy X-ray absorptiometry scan (DEXA) in line with routine laboratory investigations. Results: There was a significant increase in the serum level of DKK-1 in the patient group compared to the control group. The DKK-1 levels were 2540.65 (2215.4 - 2909.2) pg/ml and 1110.45 (885.45 - 1527.65) pg/ml, respectively, with a p-value of less than 0.001. In the hemodialysis group, 25 patients (62.5%) had low bone mineral density (BMD) with a Z-score of under -2.0. Eighteen of these patients had low BMD in both the neck of the femur and lumbar spines. Additionally, there was a significant increase in serum DKK-1 level in patients with low BMD (2567.35 (2303.8 - 3108.1) pg/ml) compared to patients with normal BMD (2454 (1859 - 2820) pg/ml) (p = 0.041). There was also a significant positive correlation between DKK1 level and phosphorus, alkaline phosphatase, and Parathormone serum levels. In conclusion, the study indicates a clear correlation between DKK-1 and BMD in children undergoing maintenance hemodialysis. DKK1 is a promising biomarker for CKD-MBD.展开更多
目的:探讨血清基质金属蛋白酶-1(matrix metalloproteinase-1,MMP1)和纽约食管鳞状细胞癌抗原-1(New York esophageal squamous cell carcinoma 1,NY-ESO-1)自身抗体联合检测在食管鳞状细胞癌中的诊断意义。方法:应用酶联免疫吸附实验检...目的:探讨血清基质金属蛋白酶-1(matrix metalloproteinase-1,MMP1)和纽约食管鳞状细胞癌抗原-1(New York esophageal squamous cell carcinoma 1,NY-ESO-1)自身抗体联合检测在食管鳞状细胞癌中的诊断意义。方法:应用酶联免疫吸附实验检测120例食管鳞状细胞癌患者和120例正常对照血清中MMP1和NY-ESO-1自身抗体的表达水平,采用受试者工作特征(receiver operating characteristic,ROC)曲线评价诊断效能。结果:血清MMP1和NY-ESO-1自身抗体在食管鳞状细胞癌患者中的表达均明显高于正常对照[(8.070±5.738)ng/mL vs(4.331±3.137)ng/mL,Z=6.214,P<0.001;0.463±0.571 vs 0.156±0.086,Z=5.210,P<0.001]。ROC曲线显示,当血清MMP1为最佳诊断临界值10.586 ng/mL时,其在诊断食管鳞状细胞癌的曲线下面积(area under the ROC curve,AUC)为0.732(95%CI:0.671~0.787),敏感度为24.2%,特异度为95.0%。NY-ESO-1自身抗体诊断食管鳞状细胞癌AUC为0.695(95%CI:0.632~0.752),敏感度为33.0%,特异度为95.0%。MMP1和NY-ESO-1自身抗体联合检测诊断食管鳞状细胞癌的AUC为0.800(95%CI:0.744~0.849),敏感度为47.5%,特异度为95.0%。结论:血清MMP1和NY-ESO-1自身抗体联合检测可能有助于提高食管鳞状细胞癌的诊断效能。展开更多
目的探讨Wnt-1、Dickkopf相关蛋白1(DKK-1)、红细胞分布宽度(red cell distribution width,RDW)与冠心病的相关性,并分析Wnt-1、DKK-1和RDW之间的内在联系及其对冠心病的联合诊断价值。方法选取行冠状动脉(简称冠脉)造影的住院患者188例...目的探讨Wnt-1、Dickkopf相关蛋白1(DKK-1)、红细胞分布宽度(red cell distribution width,RDW)与冠心病的相关性,并分析Wnt-1、DKK-1和RDW之间的内在联系及其对冠心病的联合诊断价值。方法选取行冠状动脉(简称冠脉)造影的住院患者188例,根据冠脉造影结果将其分为冠心病组(n=128)和非冠心病组(n=60)并收集临床资料,比较两组间的Wnt-1、DKK-1、RDW差异。结果冠心病组患者血清Wnt-1水平降低,而DKK-1、RDW升高,与非冠心病组相比差异均有统计学意义(P<0.05);冠心病组中的急性心肌梗死组(30例)、不稳定型心绞痛组(54例)和稳定型心绞痛组(44例)三个亚组间Wnt-1、DKK-1及RDW差异均无统计学意义(P>0.05)。经Logistic回归分析,Wnt-1、DKK-1、RDW的OR值分别为0.947、1.023、64.995。三者联合诊断冠心病的受试者工作特征曲线下面积为0.977(95%CI 0.958~0.997),敏感性为92.2%,特异性为96.7%。结论DKK-1、RDW可能为发生冠心病的独立危险因素,Wnt-1可能为发生冠心病的独立保护因素。Wnt-1、DKK-1、RDW三者联合高于上述任一指标单独对冠心病的诊断价值。展开更多
BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by th...BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens.Like neutrophils in the context of innate immune responses,immunoglobulin A(IgA)as an acquired immune response partakes in the defense of the intestinal epithelium.Under normal conditions,IgA contributes to the elimination of microbes,but in connection with the loss of tolerance to chitinase 3-like 1(CHI3L1)in IBD,IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms.The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target,the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear.AIM To determine the predictive potential of Ig subtypes of a novel serological marker,anti-CHI3L1 autoantibodies(aCHI3L1)in determining the disease phenotype,therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients.METHODS Sera of 257 Crohn’s disease(CD)and 180 ulcerative colitis(UC)patients from a tertiary IBD referral center of Hungary(Division of Gastroenterology,Department of Internal Medicine,Faculty of Medicine,University of Debrecen)were assayed for IgG,IgA,and secretory IgA(sIgA)type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1,along with 86 healthy controls(HCONT).RESULTS The IgA type was more prevalent in CD than in UC(29.2%vs 11.1%)or HCONT(2.83%;P<0.0001 for both).However,sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT(39.3%and 32.8%vs 4.65%,respectively;P<0.0001).The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement(P<0.0001 and P=0.038,respectively)in patients with CD.Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity(57.1%vs 36.0%,P=0.009).IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group(46.9%vs 25.7%,P=0.005).In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis,positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models.This association disappeared after merging subgroups of different disease locations.CONCLUSION CHI3L1 is a novel neutrophil autoantigenic target in IBD.The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.展开更多
BACKGROUND In recent years,the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediat...BACKGROUND In recent years,the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes(T1D).While it has been established that 20%-30%of T1D patients suffer from autoimmune thyroid disease(AITD),there is limited available data regarding the presence of anti-islet autoantibodies in AITD patients.Among commercially available anti-islet autoantibodies,glutamic acid decarboxylase 65 autoantibodies(GADAs)are often the first marker measured in general clinical practice.AIM To investigate the frequency of anti-islet autoantibodies in AITD patients.METHODS Our study involved four hundred ninety-five AITD patients,categorized into three distinct groups:AITD with T1D(n=18),AITD with phenotypic type 2 diabetes(T2D)(n=81),and AITD without diabetes(n=396),and the enzyme-linked immunosorbent assay(ELISA)was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody(3 Screen ICA),GADA,insulinoma-associated antigen-2 autoantibodies(IA-2As),and zinc transporter 8 autoantibodies(ZnT8As)within these groups.RESULTS The frequency of 3 Screen ICA in AITD patients with T1D,T2D,and those without diabetes were 88.9%,6.2%,and 5.1%,respectively,with no significant difference seen between the latter two groups.Notably,the frequency of 3 Screen ICA was 11.1%higher in AITD patients with T1D,1.3%higher in AITD patients with T2D,and 1.1%higher in AITD patients without diabetes compared to GADA,respectively.Furthermore,12.5%,20.0%,and 20.0%of the 3 Screen ICA-positive patients were negative for GADA.Additionally,1.3%of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual autoantibodies.Among the 3 Screen ICA-positive patients,there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D compared to those without diabetes(37.5%vs 5.0%,P<0.05).However,this proportion was similar to that in AITD patients with T2D(20.0%).Nevertheless,there was no significant difference in 3 Screen ICA titers between AITD patients with T1D and those without diabetes(436.8±66.4 vs 308.1±66.4 index).Additionally,no significant difference in 3 Screen ICA titers was observed between Graves’disease and Hashimoto’s thyroiditis in any of the groups.CONCLUSION Our findings reveal that some AITD patients without diabetes exhibit 3 Screen ICA titers comparable to those in AITD patients with T1D.Thus,3 Screen ICA outperforms GADA in identifying latent anti-islet autoantibody-positive individuals among AITD patients.展开更多
文摘Background: Renal osteodystrophy (ROD) is a bone disorder resulting from chronic kidney disease (CKD) and related metabolic diseases. Dickkopf-related protein-1 (DKK-1) is critical in regulating bone biology. This study aimed to evaluate the serum DKK-1 level as a bone marker in children with CKD who undergo regular hemodialysis (HD). Subjects and Methods: This case-control study involved 40 children with CKD on HD and 40 healthy children as controls. The study measured serum DKK-1 levels and performed a dual-energy X-ray absorptiometry scan (DEXA) in line with routine laboratory investigations. Results: There was a significant increase in the serum level of DKK-1 in the patient group compared to the control group. The DKK-1 levels were 2540.65 (2215.4 - 2909.2) pg/ml and 1110.45 (885.45 - 1527.65) pg/ml, respectively, with a p-value of less than 0.001. In the hemodialysis group, 25 patients (62.5%) had low bone mineral density (BMD) with a Z-score of under -2.0. Eighteen of these patients had low BMD in both the neck of the femur and lumbar spines. Additionally, there was a significant increase in serum DKK-1 level in patients with low BMD (2567.35 (2303.8 - 3108.1) pg/ml) compared to patients with normal BMD (2454 (1859 - 2820) pg/ml) (p = 0.041). There was also a significant positive correlation between DKK1 level and phosphorus, alkaline phosphatase, and Parathormone serum levels. In conclusion, the study indicates a clear correlation between DKK-1 and BMD in children undergoing maintenance hemodialysis. DKK1 is a promising biomarker for CKD-MBD.
文摘目的:探讨血清基质金属蛋白酶-1(matrix metalloproteinase-1,MMP1)和纽约食管鳞状细胞癌抗原-1(New York esophageal squamous cell carcinoma 1,NY-ESO-1)自身抗体联合检测在食管鳞状细胞癌中的诊断意义。方法:应用酶联免疫吸附实验检测120例食管鳞状细胞癌患者和120例正常对照血清中MMP1和NY-ESO-1自身抗体的表达水平,采用受试者工作特征(receiver operating characteristic,ROC)曲线评价诊断效能。结果:血清MMP1和NY-ESO-1自身抗体在食管鳞状细胞癌患者中的表达均明显高于正常对照[(8.070±5.738)ng/mL vs(4.331±3.137)ng/mL,Z=6.214,P<0.001;0.463±0.571 vs 0.156±0.086,Z=5.210,P<0.001]。ROC曲线显示,当血清MMP1为最佳诊断临界值10.586 ng/mL时,其在诊断食管鳞状细胞癌的曲线下面积(area under the ROC curve,AUC)为0.732(95%CI:0.671~0.787),敏感度为24.2%,特异度为95.0%。NY-ESO-1自身抗体诊断食管鳞状细胞癌AUC为0.695(95%CI:0.632~0.752),敏感度为33.0%,特异度为95.0%。MMP1和NY-ESO-1自身抗体联合检测诊断食管鳞状细胞癌的AUC为0.800(95%CI:0.744~0.849),敏感度为47.5%,特异度为95.0%。结论:血清MMP1和NY-ESO-1自身抗体联合检测可能有助于提高食管鳞状细胞癌的诊断效能。
文摘目的探讨Wnt-1、Dickkopf相关蛋白1(DKK-1)、红细胞分布宽度(red cell distribution width,RDW)与冠心病的相关性,并分析Wnt-1、DKK-1和RDW之间的内在联系及其对冠心病的联合诊断价值。方法选取行冠状动脉(简称冠脉)造影的住院患者188例,根据冠脉造影结果将其分为冠心病组(n=128)和非冠心病组(n=60)并收集临床资料,比较两组间的Wnt-1、DKK-1、RDW差异。结果冠心病组患者血清Wnt-1水平降低,而DKK-1、RDW升高,与非冠心病组相比差异均有统计学意义(P<0.05);冠心病组中的急性心肌梗死组(30例)、不稳定型心绞痛组(54例)和稳定型心绞痛组(44例)三个亚组间Wnt-1、DKK-1及RDW差异均无统计学意义(P>0.05)。经Logistic回归分析,Wnt-1、DKK-1、RDW的OR值分别为0.947、1.023、64.995。三者联合诊断冠心病的受试者工作特征曲线下面积为0.977(95%CI 0.958~0.997),敏感性为92.2%,特异性为96.7%。结论DKK-1、RDW可能为发生冠心病的独立危险因素,Wnt-1可能为发生冠心病的独立保护因素。Wnt-1、DKK-1、RDW三者联合高于上述任一指标单独对冠心病的诊断价值。
基金Supported by the German Federal Ministry of Education and Research(BMBF-Wachstumskern-PRAEMED.BIO),03WKDB2Csupported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences,BO/00232/17/5+1 种基金Research Grants of National Research Development and Innovation Office,K115818/2015/1New National Excellence Program of the Ministry of Human Capacities,ÚNKP-18-4 Bolyai Plus.
文摘BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens.Like neutrophils in the context of innate immune responses,immunoglobulin A(IgA)as an acquired immune response partakes in the defense of the intestinal epithelium.Under normal conditions,IgA contributes to the elimination of microbes,but in connection with the loss of tolerance to chitinase 3-like 1(CHI3L1)in IBD,IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms.The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target,the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear.AIM To determine the predictive potential of Ig subtypes of a novel serological marker,anti-CHI3L1 autoantibodies(aCHI3L1)in determining the disease phenotype,therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients.METHODS Sera of 257 Crohn’s disease(CD)and 180 ulcerative colitis(UC)patients from a tertiary IBD referral center of Hungary(Division of Gastroenterology,Department of Internal Medicine,Faculty of Medicine,University of Debrecen)were assayed for IgG,IgA,and secretory IgA(sIgA)type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1,along with 86 healthy controls(HCONT).RESULTS The IgA type was more prevalent in CD than in UC(29.2%vs 11.1%)or HCONT(2.83%;P<0.0001 for both).However,sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT(39.3%and 32.8%vs 4.65%,respectively;P<0.0001).The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement(P<0.0001 and P=0.038,respectively)in patients with CD.Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity(57.1%vs 36.0%,P=0.009).IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group(46.9%vs 25.7%,P=0.005).In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis,positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models.This association disappeared after merging subgroups of different disease locations.CONCLUSION CHI3L1 is a novel neutrophil autoantigenic target in IBD.The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.
文摘BACKGROUND In recent years,the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes(T1D).While it has been established that 20%-30%of T1D patients suffer from autoimmune thyroid disease(AITD),there is limited available data regarding the presence of anti-islet autoantibodies in AITD patients.Among commercially available anti-islet autoantibodies,glutamic acid decarboxylase 65 autoantibodies(GADAs)are often the first marker measured in general clinical practice.AIM To investigate the frequency of anti-islet autoantibodies in AITD patients.METHODS Our study involved four hundred ninety-five AITD patients,categorized into three distinct groups:AITD with T1D(n=18),AITD with phenotypic type 2 diabetes(T2D)(n=81),and AITD without diabetes(n=396),and the enzyme-linked immunosorbent assay(ELISA)was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody(3 Screen ICA),GADA,insulinoma-associated antigen-2 autoantibodies(IA-2As),and zinc transporter 8 autoantibodies(ZnT8As)within these groups.RESULTS The frequency of 3 Screen ICA in AITD patients with T1D,T2D,and those without diabetes were 88.9%,6.2%,and 5.1%,respectively,with no significant difference seen between the latter two groups.Notably,the frequency of 3 Screen ICA was 11.1%higher in AITD patients with T1D,1.3%higher in AITD patients with T2D,and 1.1%higher in AITD patients without diabetes compared to GADA,respectively.Furthermore,12.5%,20.0%,and 20.0%of the 3 Screen ICA-positive patients were negative for GADA.Additionally,1.3%of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual autoantibodies.Among the 3 Screen ICA-positive patients,there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D compared to those without diabetes(37.5%vs 5.0%,P<0.05).However,this proportion was similar to that in AITD patients with T2D(20.0%).Nevertheless,there was no significant difference in 3 Screen ICA titers between AITD patients with T1D and those without diabetes(436.8±66.4 vs 308.1±66.4 index).Additionally,no significant difference in 3 Screen ICA titers was observed between Graves’disease and Hashimoto’s thyroiditis in any of the groups.CONCLUSION Our findings reveal that some AITD patients without diabetes exhibit 3 Screen ICA titers comparable to those in AITD patients with T1D.Thus,3 Screen ICA outperforms GADA in identifying latent anti-islet autoantibody-positive individuals among AITD patients.
