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Abstract Objective: The incidence and prevalence of inflammatory bowel disease (IBD) in pediatric patients are increasing. Currently, the diagnostic method for IBD is inconvenient, expensive, and difficult. S100A12, a type of calcium-binding protein, detected in the feces of patients with IBD has recently been suggested as a promising diagnostic tool. Hence, the authors aimed to evaluate the accuracy of fecal S100A12 in diagnosing IBD in pediatric patients by performing a meta-analysis. Methods: The authors performed a systematic literature search in five electronic databases for eligible studies up to July 15, 2021. Pooled diagnostic accuracies of fecal S100A12 were analyzed as the primary outcomes. Secondary outcomes were standardized mean difference (SMD) of fecal S100A12 levels between IBD and non-IBD groups and a comparison of diagnostic accuracies between fecal S100A12 and fecal calprotectin. Results: Seven studies comprising 712 children and adolescents (474 non-IBD controls and 238 IBD cases) were included. Fecal S100A12 levels were higher in the IBD group than in the non-IBD group (SMD = 1.88; 95% confidence interval [CI] = 1.19-2.58; p < 0.0001). Fecal S100A12 could diagnose IBD in pediatric patients with a pooled sensitivity of 95% (95% CI = 88%-98%), specificity of 97% (95% CI = 95%-98%), and area under the receiver operating summary characteristics (AUSROC) curve of 0.99 (95% CI = 0.97-0.99). Fecal S100A12 specificity and AUSROC curve values were higher than those of fecal calprotectin (p < 0.05). Conclusion: Fecal S100A12 may serve as an accurate and non-invasive tool for diagnosing pediatric IBD. © 2023 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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BACKGROUND: Inflammatory transmitters secreted from the synovium may be one of the important factors inducing the onset of knee osteoarthritis, and further exacerbate knee osteoarthritis. OBJECTIVE: To observe the effect of different concentrations of catalpol from the root of Rehmannia glutinosa on the expression of interleukin-1β, galectin 3 and S100A12 in the synovium of the knee joint in rats with early knee osteoarthritis, and to explore the mechanism of catalpol from the root of Rehmannia glutinosa in the treatment of early knee osteoarthritis. METHODS: The 14 of 48 adult male Wistar rats were randomly selected as a normal control group, and the remaining 34 rats were injected with 4% papain and 0.03 mol/L cysteine solution (0.2 mL) into the right knee joint cavity at 1, 4, 7 days after the initialization of the experiment to duplicate the model of early knee osteoarthritis. At 10 days after the initialization of the experiment, 4 rats in each group were randomly selected for histological observation using hematoxylin-eosin staining and validation of the model using Mankin and OARSI grading evaluation. After the model was successfully verified, the remaining 30 rats in the model group were randomly divided into model control group, low-dose group and high-dose group. At 2 days after successful modeling, each treatment group was infused with corresponding drugs at a dose of 0.2 mL/kg, and normal control group and model control group were infused with normal saline, once a day for 28 consecutive days. The synovium of the right knee joint was then taken from rats in each group, and the expression of interleukin-1β, galectin 3 and S100A12 in the rat synovium was detected by ELISA. RESULTS AND CONCLUSION: Mankin score and OARSI grading were significantly higher in the model control group than the normal control group (P < 0.05). The levels of S100A12, interleukin-1β and galectin 3 in the synovium were significantly higher in the model control group than the normal control group (P < 0.01). Compared with the model control group, the levels of S100A12, interleukin-1β and galectin 3 in the synovium was decreased somewhat in the low-dose group (P < 0.05), but significantly decreased in the high-dose group (P < 0.01). Therefore, catalpol from the root of Rehmannia glutinosa can delay the progression of knee osteoarthritis by reducing the level of inflammatory factors in the synovium.
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BACKGROUND AND OBJECTIVE: The diagnosis and evaluation of inflammatory bowel disease is quite complex. An ideal, noninvasive marker for this disease is quite urgently needed. Fecal S100A12 is a member of the S100 protein family and is secreted by activated neutrophils. We aim to evaluate it as a biomarker for inflammatory bowel disease patients in China. METHODS: Fecal S100A12 was measured in 18 Crohn's disease, 21 ulcerative colitis, and 17 healthy controls. Diagnostic value was evaluated by receiver operating characteristic (ROC) analysis in comparison with C-reactive protein and erythrocyte sedimentation rate. The correlation between fecal S100A12 and clinical characteristics was also evaluated. RESULTS: We found significant increases (p<0.01) in the diagnostic value of S100A12 in both Ulcerative Colitis and Crohn's Disease when compared to healthy controls. In ulcerative colitis, fecal S100A12 correlated with fecal occult blood (p=0.02, r=0.55); in Crohn's disease, it correlated with disease duration, albumin and platelet levels (p=0.01, r=-0.53; p<0.01, r=-0.65; p=0.04, r=0.45. respectively). No correlation occurred between fecal S100A12 and other clinical conditions. CONCLUSION: Fecal S100A12 is valuable in distinguishing inflammatory bowel disease patients versus healthy controls. However, the sensitivity and specificity are limited when compared with that described in western countries. The correlation between S100A12 and clinical characteristics is limited as well. More research is need to better explore this interaction in Chinese patients.
JUSTIFICATIVA E OBJETIVO: O diagnóstico e avaliação da doença inflamatória intestinal é bastante complexo. Um marcador ideal, não invasivo para esta doença é urgentemente necessário. O S100A12 fecal é um membro da família de proteínas S100 e é secretado por neutrófilos ativados. Pretendemos avaliá-lo como biomarcador para pacientes com doença inflamatória intestinal na China. MÉTODOS: a proteína fecal S100A12 foi medida em 18 pacientes com Moléstia de Crohn, 21 pacientes com Colite Ulcerativa e 17 voluntários saudáveis (controles). O valor diagnóstico foi avaliado através da análise da característica de operação do receptor (ROC) em comparação com a proteína C reativa e com a taxa sedimentação eritrocitária. A correlação entre S100A12 fecal e características clínicas também foi avaliada. RESULTADOS: Observamos aumentos significativos (p < 0.01) no valor diagnóstico de S100A12 tanto na Colite Ulcerativa quanto na Doença de Crohn quando comparados aos controles saudáveis. Na colite ulcerativa, a proteína S100A12 fecal correlacionou com sangue oculto fecal (p = 0,02, r = 0,55); Na doença de Crohn, correlacionou com a duração da doença, albumina e níveis de plaquetas (p = 0,01, r = -0,53; p <0,01, r = -0,65; p = 0,04, r = 0,45, respectivamente). Não houve correlação entre S100A12 fecal e outras condições clínicas. CONCLUSÃO: O S100A12 fecal é valioso para distinguir pacientes com doença inflamatória intestinal versus controles saudáveis. No entanto, a sensibilidade e especificidade é limitada quando comparada com a descrita nos países ocidentais. A correlação entre S100A12 e características clínicas é limitada. Mais pesquisas são necessárias para explorar melhor essa interação em pacientes chineses.
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Humans , Colitis, Ulcerative/diagnosis , Crohn Disease/diagnosis , S100A12 Protein/analysis , Occult Blood , Biomarkers/analysis , ChinaABSTRACT
Objective To investigate the correlation and significance of S100A12 with obstructive sleep apnea hypopnea syndrome (OSAHS).Methods Fifty-three patients with OSAHS were chosen as OSAHS group and 46 healthy volunteers were chosen as control group.The levels of S100A12 and hs-CRP in the two groups were compared,and its relationship with those of epworth (ESS),apnea hypopnea index (AHI),and minimum blood oxygen saturation (L-SpO2) were analysised.Results The scores of ESS,BMI,A HI,L-SpO2,hs-CRP and S100A12 in two groups were statistically significant (P＜0.05).The severity of hs-CRP in severe OSAHS group was significantly higher than that of mild OSAHS group (P＜0.05).There was no significant difference in hs-CRP between moderate OSAHS group and mild OSAHS group and severe group (P＞0.05).The level of S100A12 in severe OSAHS group was significantly higher than that of moderate OSAHS group and OSAHS mild group(P＜0.05).The level of S100A12 in moderate moderate group was significantly higher than that of mild group(P＜0.01).hs-CRP was negatively correlated with ESS and AHI (r=0.822,0.787,P＜0.01),was positively correlated with L-SpO2 (r=-0.740,P＜0.01),S100A12 was positively correlated with ESS and AHI (r =0.707,P ＜ 0.01),and negatively correlated with ESS and AHI (r =0.707,0.807,P＜0.01),and negatively correlated with with L-SpO2 (r=-0.670,P＜0.01).Conclusion S100A12 is associated with OSAHS.The higher the severity of OSAHS,the higher the S100A12 value,which can be used as a new predictor of cardiovascular disease risk in OSAHS patients.
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Objective To analyze the relationship between the level of serum calcium binding protein S 100A12 and the severity of acute pancreatitis (AP) ,so as to provide a simple and reliable method for judging the severity of AP .Methods A total of 68 pa-tients with AP from January 2015 to January 2016 in Luzhou Hospital of Traditional Chinese Medicine were selected as objects in this study ,and complete the examination after diagnosis ,modified CT severity index (MCTSI) was used to grade the severity ,serum calcium binding protein S100A12were tested and compared in patients with different disease grading .The ROC curve of different se-verity patients were made .Judging the severity of critical value according to the S 100A12 curve inflection point ,basing on the judg-ment of MCTSI ,the sensitivity ,specificity and accuracy of S 100A12 in grading condition of AP were calculated ,then the value of S100A12 was evaluated .Results The level of S100A12 increased with MCTSI grade rising ,there were significant differences in S100A12 level between different grades patients(P<0 .05) .ROC curve analysis showed that the clinical limits of gradeⅠto Ⅲ were 26-80 ,81-260 ,>260 ng/mL respectively .The sensitivities accuracy of S100A12 judging grade Ⅰ ,grade Ⅱ and grade Ⅲ were 88 .89% ,94 .12% ,80 .00% ,the specificity were 75 .00% ,94 .12% ,96 .55% ,the accuracy were 82 .35% ,94 .12% ,94 .12% respec-tively .Conclusion The serum calcium binding protein S100A12 estimates is consistent with MCTSI for judging the severity condi-tion of AP .
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Objective To analyze the relationship between the level of serum calcium binding protein S 100A12 and the severity of acute pancreatitis (AP) ,so as to provide a simple and reliable method for judging the severity of AP .Methods A total of 68 pa-tients with AP from January 2015 to January 2016 in Luzhou Hospital of Traditional Chinese Medicine were selected as objects in this study ,and complete the examination after diagnosis ,modified CT severity index (MCTSI) was used to grade the severity ,serum calcium binding protein S100A12were tested and compared in patients with different disease grading .The ROC curve of different se-verity patients were made .Judging the severity of critical value according to the S 100A12 curve inflection point ,basing on the judg-ment of MCTSI ,the sensitivity ,specificity and accuracy of S 100A12 in grading condition of AP were calculated ,then the value of S100A12 was evaluated .Results The level of S100A12 increased with MCTSI grade rising ,there were significant differences in S100A12 level between different grades patients(P<0 .05) .ROC curve analysis showed that the clinical limits of gradeⅠto Ⅲ were 26-80 ,81-260 ,>260 ng/mL respectively .The sensitivities accuracy of S100A12 judging grade Ⅰ ,grade Ⅱ and grade Ⅲ were 88 .89% ,94 .12% ,80 .00% ,the specificity were 75 .00% ,94 .12% ,96 .55% ,the accuracy were 82 .35% ,94 .12% ,94 .12% respec-tively .Conclusion The serum calcium binding protein S100A12 estimates is consistent with MCTSI for judging the severity condi-tion of AP .
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Hemodialysis (HD) patients experience vascular calcification, ultimately leading to high mortality rates. Previously, we reported associations between soluble receptor for advanced glycation end products (sRAGEs) and extracellular newly identified RAGE-binding protein S100A12 (EN-RAGE) and vascular calcification. Here, we extended our observations, investigating whether these biomarkers may be useful for predicting cardiovascular morbidity and mortality in these subjects. Thus, we evaluated the relationship between sRAGE and S100A12 and mortality in long-term HD patients. This was a prospective observational cohort study in 199 HD patients from an extended analysis of our previous study. Plasma sRAGE, S100A12, comorbidities, and other traditional risk factors were investigated. The cumulative incidences for death using Cox proportional hazards regression were evaluated in multivariable analyses. The observation period was 44 months. During the observation period, 27 (13.6%) patients died. Univariate analysis demonstrated that S100A12 was correlated with diabetes (P = 0.040) and high-sensitivity C-reactive protein (hsCRP) (P = 0.006). In multivariable analyses, plasma sRAGE (hazard ratio [HR] = 1.155; 95% confidence interval [CI] = 0.612–2.183; P = 0.656) and S100A12 (HR = 0.960; 95% CI = 0.566–1.630; P = 0.881) were not associated with mortality in HD patients, although traditional predictors of mortality, including age, history of cardiovascular diseases (CVDs), and serum levels of albumin and hsCRP were related to mortality. Powerful predictors of mortality were age, CVD, and albumin levels. Plasma sRAGE and S100A12 may be weak surrogate markers for predicting all-cause mortality in patients undergoing HD, although S100A12 was partly related to diabetes and inflammation.
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Humans , Biomarkers , C-Reactive Protein , Cardiovascular Diseases , Cohort Studies , Comorbidity , Incidence , Inflammation , Mortality , Plasma , Prospective Studies , Renal Dialysis , Risk Factors , S100A12 Protein , Vascular CalcificationABSTRACT
Objective To study the significance of S100A12 in patients with acute pancreatitis (AP).Methods 139 patients with AP were divided into the severe acute pancreatitis (SAP) and moderate acute pancreatitis (MAP) groups.61 patients in the SAP group were further subdivided into the infection group (n =32) and the non-infection group (n =29) based on the presence/absence of secondary infection.Serum samples of these patients were collected on the 3rd,7th and 14th day after treatment.ELISA was used to determinate the S100A12,IL-1 β and IL-6 levels in serum.The area under ROC was used to evaluate the predictive role of S100A12,IL-1β,IL-6 and CRP for infection in patients with SAP.Results The S100A12,IL-1β and IL-6 levels in SAP patients were markedly higher than those in MAP patients and normal controls on the 3rd,7th and 14th day after treatment.These levels decreased toward normal range in MAP patients.They were persistently high in SAP patients after treatment for 7 days,but decreased significantly after 14 days.The serum levels of S100A12,IL-1β,IL-6 and CRP were significantly higher in the infection subgroup(647.5 ± 300.1,155.9 ±48.5,95.7 ±25.5,166.8 ±53.0) than the non-infection subgroup(249.0 ± 176.3,108.0 ± 46.1,64.0 ±38.5,117.9 ±34.9) (P ＜0.05).The sensitivity and specificity of serum S100A12 in diagnosing secondary infection in SAP were 96.8％ and 83.3％,which were higher than those of serum IL-1β,IL-6 or CRP.Conclusion The level of S100A12 was associated with systemic inflammatory response syndrome (SIRS) in AP,and it may serve as a new marker in early diagnosis of SAP and in secondary infection in SAP.
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Objective To evaluate the correlation between human serum S100A12 level and severity of acute pancreatitis (AP).Methods Serum S100A12 were tested in 64 AP patients in 24 hours after the onset.S 100A12 levels was compared to the severity of AP,and the area under the curve (AUC) of the receiver operating characteristic curve(ROC) of serum S100A12 levels for estimating the severity of AP were made and compared with laboratory parameters and APACHE-Ⅱ,Ranson' s scoring system.Results S100A12 levels in early AP patients were higher than healthy controls (P ＜ 0.05).S100A12 levels increased and correlated with MCTSI scores:patients scored 7-8 ＞ patients scored 4-6 ＞patients scored less than 4 (P ＜ 0.01).S100A 12 levels increased with organ failure (P ＜ 0.01).The AUC of S100A12 in 24 hours after onset for distinguishing MAP between MSAP and SAP was 0.80,cut-off point was 61.83 ng/ml,sensitivity was 70.01％ and the specificity was 73.52％.Serum S100A12 levels were higher in SAP than in MSAP(P =0.01).The AUC of S100A12 in early AP for distinguishing between MSAP and SAP was 0.84,cut-off point was 285.32 ng/ml,the sensitivity was 76.94％ and the specificity was 94.12％,Youden index was 71.00％,positive likelihood ratio was 13.00,negative likelihood ratio was 0.20,the diagnostic performance was better than APACHE-Ⅱ,Ranson and Marshall scoring systems and serum CRP concentration.Conclusions Human serum S100A12 levels elevated at early stage of AP.S100A12 ＞285.32 ng/ml represents high risk of SAP,which is more sensitive and accurate than APACHE-Ⅱ and Marshall scoring system.
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Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterised by periodic inflammatory attacks. We investigated changes in monocyte-granulocyte derived S10012A and chitotriosidase in both the attack and silent period of FMF for better estimation of inflammation. Endogenous resolvin was determined for utility to restrict inflammation. This study included 29 FMF patients (15 M/14 F) and 30 healthy controls (15 M/15 F). Serum levels of highly sensitive C-reactive protein, serum amiloid A (SAA), S100A12, chitotriosidase, and resolvin D1 were measured. Age, sex, body mass indexes, and lipids were similar between patients and controls. Biomarkers including hs-CRP, SAA, S100A12, chitotriosidase, and resolvin D1 were higher in the attack period of FMF patients compared to controls (P < 0.001). When FMF patients in the silent period were compared with their attack period, hs-CRP, SAA, and chitotriosidase were found elevated in the attack period (P < 0.001, P < 0.001, and P = 0.02 respectively). Serum levels of SAA, S100A12, chitotriosidase, and resolvin D1 in the silent period of FMF patients were still found elevated compared to healthy controls, indicating subclinical inflammation (P < 0.001, P < 0.001, P = 0.009, and P < 0.001 respectively ). In subgroup analysis, patients with M694V homozygote and heterozygote mutations had higher S10012A and hs-CRP compared to other mutation carriers. Our findings indicate that chitotriosidase and S10012A are useful in diagnosis and detection of subclinical inflammation and/or assessment of disease activity in FMF patients. They could be more informative for inflammation in various disease states compared to hsCRP and SAA. Resolvin D1 is elevated in both the attack and silent periods of FMF. It may be helpful to restrict inflammation.
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Adult , Female , Humans , Male , Biomarkers , Docosahexaenoic Acids/blood , Familial Mediterranean Fever/blood , Feasibility Studies , Hexosaminidases/blood , Reproducibility of Results , S100A12 Protein/blood , Sensitivity and SpecificityABSTRACT
Objective To examine the kinetics of plasma S100A12 and soluble receptor for advanced glycation end products (sRAGE) in infants and young children undergoing cardiopulmonary bypass ( CPB),and to investigate whether they could protective the occurrence of noninfectious pulmonary complication (NPC) after cardiac surgery.Methods This was a case-control study.The subjects included all children aged ＜3 years old who underwent cardiac surgery with CPB during the period from June 1st to July 31st 2011.The patient who showed pulmonary inflammation or had abnormal liver or renal function before surgery was excluded.The remain patients were divided into 2 groups according to whether they had developed NPC postoperatively.Twenty patients were grouped into NPC because they developed the complications of pleural effusion,chylothorax,partial lung collapse,pulmonary hypertensive crisis,airway disorders,pneumothorax,pneumomediastinum,or phrenic nerve palsy.Forty patients were categorized into the no-NPC group.Plasma concentrations of S100A12 and sRAGE were measured using ELISA at baseline,before CPB,immediately after CPB,1 h,12 h and 24 h after operation.Differences concentrations between two groups were analyzed with t test.A stepwise logistic regression analysis was used to indentify the independent risk factor for NPC.A P value ＜0.05 was considered statistically significant.Results Plasma levels of S100A12 and sRAGE dramatically increased immediately after CPB ( P ＜ 0.01 ).The levels of sRAGE dropped to lower than baseline level (P ＜0.05),while S100A12 was still at high level 24h after operation (P ＜0.01 ).Levels of S100A12 and sRAGE immediately after CPB in NPC group were significantly higher than the no-NPC group (P ＜ 0.05).Twenty-four hours after operation,levels of S100A12 were still higher in NPC group than no-NPC (P ＜ 0.01 ),while levels of sRAGE were similar in the two groups ( P ＞ 0.05 ).In the stepwise logistic regression analysis,plasma S100A12 level immediately after CPB remained as a independently predictor for postoperative NPC (OR =1.042,95％ CI:1.010 ～ 1.076,P =0.011 ).Levels of S100A12 immediately after CPB were positively associated with mechanical ventilation time ( r =0.47,P ＜ 0.01 ),duration of surgical Intensive Care Unit ( r =0.407,P =0.002) and hospital stay ( r =0.421,P =0.01 ).Conclusions Plasma levels of S100A12 and sRAGE were significantly increased immediately after CPB and the elevated plasma S100A12 immediately after CPB served as an early reliable biomarker of the occurrence and the prognosis of NPC after CPB in infants and young children.
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BACKGROUND: S100A12 is a member of the S100 family of calcium-binding proteins and is secreted either in inflamed tissues or in the bloodstream by activated neutrophils. Expression of S100A12 has been reported in various diseases, especially non-infectious inflammatory diseases, such as Kawasaki disease, giant cell arteritis and inflammatory bowel disease. OBJECTIVE: This study was conducted to determine both the tissue expression and the serum levels of S100A12 in Behcet's disease (BD) patients and the correlation of the S100A12 serum level with disease activity of BD. METHODS: We included in this study ten BD patients who fulfilled the criteria for diagnosis, according to the International Study Group for BD. The activity of BD was calculated using the BD Current Activity Form. The serum concentrations of both S100A12 and interleukin-8 were measured by the enzyme-linked immunosorbent assay, before and after treatment. Immunohistochemical studies were also performed to detect S100A12 expression in the skin. RESULTS: The serum S100A12 level was significantly increased in the active BD period (p<0.001), in the inactive BD period (p=0.041) and in patients with active Kawasaki disease (p=0.028), compared with the serum level in the healthy controls. The serum S100A12 level decreased significantly from baseline, compared to post-treatment (p=0.017). The activity score of BD was significantly correlated with the serum level of S100A12 (Spearman's coefficient=0.464, p=0.039). Immunohistochemical studies showed that S100A12 was strongly expressed in the erythema nodosum-like skin lesions of patients. CONCLUSION: S100A12 contributes to the pathogenesis of BD related to neutrophil hyperactivity and reflects the disease activity in BD patients.