Evaluation of fecal protein S100A12 in patients with inflammatory bowel disease / Avaliação da proteína fecal s100q12 em pacientes com doença inflamatória intestinal

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.

Associations between Soluble Receptor for Advanced Glycation End Products (sRAGE) and S100A12 (EN-RAGE) with Mortality in Long-term Hemodialysis Patients

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.

S1000A12, Chitotriosidase, and Resolvin D1 as Potential Biomarkers of Familial Mediterranean Fever

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.