| BackgroundHemophagocytic lymphohistocytosis(HLH), also known as hemophagocytic syndrome(HPS), is a serious life-threatening and easily missed ultra-inflammatory response syndrome, and is more common in childhood, with clinical manifestations of complex and diverse, the extremely rapid disease progression and high mortality rate. Early diagnosis is critical to reduce mortality of patients. Currently, because lack of a recognized high specificity diagnostic criteria and the verification gold standard, diagnosed as soon as possible remains a serious challenge for clinicians.Monocytes / macrophages hemoglobin scavenger receptor(CD163) is a transmembrane glycoprotein expressing on activated monocytes and macrophages membrane. The study showed that CD163 can directly activate monocytes and macrophages intracellular signal transduction pathways, adjust the expression of inflammatory cytokines, e.g. TNF-a, IL-6 and IL-10, play anti-inflammatory and antioxidant effects in the inflammatory response. In inflammation, the CD163 molecule from the macrophage cell membrane fall off and form a soluble s CD163. When the body is excessive activation of macrophages caused by infection, cancer, autoimmune disease, the serum s CD163 molecule expression would be significantly higher. It has become one of the hallmarks of macrophage activation. Soluble CD25(s IL-2Ra) mainly result from CD25 molecular of Treg cell, activated T/B lymphocytes and monocytes surface. s CD25 is an important immunosuppressive factors, combined with the activated IL-2R of cell surface by competing with IL-2, and reduce the activity of IL-2. and the level of CD25 and severity of inflammation is positively correlated. s CD25 is one of the indicators of T lymphocyte activation, and one of HLH diagnostic criteria.Biological function of serum s CD163 and s CD25 remain poorly understood at present, and domestic and foreign research concentrated on its expression in disease. In many diseases they have become an important serological markers and have an evaluation value. In recent researches on serum s CDl63 and s CD25 are more and more. Although serum s CD25 has emerged as one of the diagnostic criteria for HLH, but it is still not enough clinical popularity. At present clinical and pathological studies of HLH needs to be further improved.Enzyme linked immunosorbent assay(ELISA) is one of the three classic Labeled Immunoassays technology. With the advent of new technologies related to ELISA, the specificity, sensitivity and the degree of automation of the analysis and the measurement method are significantly improved. So the enzyme immunoassay constantly updated, range of applications is continuing to broaden. At present, the enzyme immunoassay technology has been widely used in medicine and biology,and it became one of commonly used in clinical and easy-to-use tests methods. ObjectiveBy detecting serum s CD163 and s CD25 levels in the peripheral blood in HLH group, non-HLH infected group and normal control group, this study was to explore the role of serum s CD163 and s CD25 levels in diagnosis of HLH, and correlation with clinical manifestations, as well as trends before and after the treatment. And to analyze diagnostic efficiency of serum s CD163 and s CD25 and the assessment role of the treatment effect of HLH. Methods42 cases of children with HLH and 32 cases of non-HLH infection children visiting to First Affiliated Hospital of Zhengzhou University pediatric clinic and ward were collected from December 2013 to December 2014, and 24 healthy children of getting to medical examination in the hospital as a normal controls group in the same period. And age, sex and living area was no significant difference(P > 0.05) among the three groups. All patients were negative for HIV antibodies, no hereditary diseases, with complete clinical data, and the subjects were informed parental consent. Children with HLH were phlebotomized 3ml fasting peripheral venous blood before treatment, two weeks after treatment and eight weeks after treatment. Children of non-HLH infected group and normal control group were phlebotomized 3ml fasting peripheral venous blood at the initial visit. All samples are placed in the general drying tube and allowed to stand at room temperature for two hours, then centrifuged in 1000 × g for 15 minutes. The supernatant specimens were packed in non-pyrogenic and ono-ndotoxin EP tubes and placed in-80 ℃ refrigerator.①Detected serum s CD163 and s CD25 levels in the peripheral blood in HLH group, non-HLH infected group and healthy control group by ELISA, and compared differences of serum s CD163 and s CD25 levels before treatment in three groups. Compared differences of serum s CD163 and s CD25 levels between different suffering cause. Compared trends of serum s CD163 and s CD25 levels before and after treatment in HLH group. ROC curve was used to evaluate the diagnosis effectiveness of serum s CD163 and s CD25 level.②Collected clinical and laboratory data of patients of HLH group, and analyzed correlation and relevance between serum s CD163 and s CD25 levels and various clinical data.Results1. Compared with the control group, serum s CD163 levels of HLH group and non-HLH infection group were increased in varying degrees, and the difference was statistically significant among the three groups(F = 71.396, P <0.05). Pairwise comparison showed that the differences were statistically significant between the groups(P <0.05). Compared with the control group, serum s CD25 levels of HLH group and non-HLH infection group were increased in varying degrees, and the difference was statistically significant among the three groups(F = 37.513, P <0.05). Pairwise comparison showed that non-HLH infection group and normal control group was not statistically significant(P >0.05), and the difference between the remaining groups was statistically significant(P <0.05). And serum s CD163 and s CD25 level were positive linear correlation, and pearson correlation coefficient r = 0.851(t = 15.848, P <0.05).2. The difference of serum s CD163 and s CD25 level among the different cause of disease in HLH group was statistically significant(P <0.05). Pairwise comparison showed that serum s CD163 and s CD25 level of tumor-associated HLH group were increased than infection-associated HLH group(P <0.05), but the difference was no statistically significant between the other groups(all P >0.05).3. Serum s CD163 and s CD25 level were decreased(P <0.05) with the extension of treatment time and improvement of the disease, and the difference between two adjacent time points was statistically significant(P <0.05).4. The correlation analysis showed that in HLH group serum s CD163 levels and blood leukocyte count, hemoglobin, platelet count and fibrinogen were negatively correlated(all P <0.05), and alanine aminotransferase, lactate dehydrogenase, serum ferritin, triglycerides, C-reactive protein and procalcitonin were positively correlated(all P <0.05), whereas serum s CD163 levels and other laboratory parameters were no significant correlation(all P >0.05). Similarly, serum s CD25 levels and blood leukocyte count, hemoglobin, platelet count, and fibrinogen were negatively correlated(all P <0.05), and lactate dehydrogenase, serum ferritin, triglycerides, C-reactive protein, s CD163 serum procalcitonin levels were positively correlated(all P <0.05), and serum s CD25 levels and other laboratory parameters were no significant correlation(all P >0.05).5. Seen from the ROC curve, serum s CD163 and s CD25 levels were used to diagnose HLH with high accuracy. When s CD163 cut-off point was 2359.08 ng / ml, the diagnostic sensitivity was 83.3%, and specificity was 83.9%. When s CD25 cut-off point was 14901.024 pg / ml, the diagnosis sensitivity was 76.2%, and specificity was 98.2%. Conclusions1. Similar to the serum s CD25, serum s CD163 be used for diagnosis of HLH. Patients of suspecting HLH and failing to meet the diagnostic criteria should be early detect serum s CD163 levels, to provide the basis for further diagnosis.2. Serum s CD163 and s CD25 levels may provide clues to the identification of tumor associated HLH and other reasons associated HLH.3. Dynamically monitoring of serum s CD163 and s CD25 level can help to determine the condition deteriorated of HLH and guide treatment. |
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