Clinical features of the children with malignancy-associated hemophagocytic syndrome in Beijing / 中华实用儿科临床杂志

Objective To investigate the clinical features,treatment and prognosis of the children with malignancy-associated hemophagocytic syndrome (MAHS) in Beijing in recent decade.Methods The clinical data of the patients with MAHS under 18 years old from July 2007 to February 2018 collected by the Society of Beijing hemophagocytic syndrome were analyzed retrospectively.Results There were 46 patients under 18 years old with MAHS in all(male 27,female 19).The patients with MAHS took up 8.9％ of the patients with hemophagocytic lymphohistiocytosis (HLH) (46/519 cases) from the area during that period.The median age of onset had 13.5 years (0.9-18.0 years).Thirty-five patients had lymphoma (76.0％),9 cases had leukemia (19.6％),1 case had myelodysplastic syndrome with refractory anemia with excess blast (RAEB-T),and 1 case had Epstein-Barr virus (EBV) associated lymphoproliferative disease (borderline tumor stage).All the patients had a fever.A half of them suffered from hepatosplenomegaly and 7 patients (15.2％) had neurological symptoms.Tbe common laboratory abnormalities included cytopenias,hemophagocytosis in bone marrow (81.8％,36/44 cases),elevated serum ferritin (87.8％,36/41 cases),and elevated sCD25 (100.0％,15/15 cases),decreased nature killer (NK) activity (61.1％,11/18 cases),and plasma EBV-DNA positive (57.9％).Four patients did not receive treatment,the rest were treated by several chemotherapy protocols including the HLH-94/2004 protocol.Five patients (10.8％) received the allogeneic hematopoietic stem cell transplantation,and 1 case received the splenectomy therapy.The mortality was 58.7％.Four heterozygous mutations of SH2D1A,UNC13D and PRF1 genes were found in 2 patients.Conclusions MAHS in children progresses rapidly,with poor prognosis,and it is often complicated with EBV infection.The children with MAHS may develop genetic defects similar to primary hemophagocytic syndrome.Nowadays,there is no standard treatment for MAHS,so the individualized treatment is to be explored.

Clinical features of the children with malignancy-associated hemophagocytic syndrome in Beijing / 中华实用儿科临床杂志

Objective@#To investigate the clinical features, treatment and prognosis of the children with malignancy-associated hemophagocytic syndrome (MAHS) in Beijing in recent decade.@*Methods@#The clinical data of the patients with MAHS under 18 years old from July 2007 to February 2018 collected by the Society of Beijing hemophagocytic syndrome were analyzed retrospectively.@*Results@#There were 46 patients under 18 years old with MAHS in all(male 27, female 19). The patients with MAHS took up 8.9% of the patients with hemophagocytic lymphohistiocytosis (HLH)(46/519 cases) from the area during that period.The median age of onset had 13.5 years (0.9-18.0 years). Thirty-five patients had lymphoma (76.0%), 9 cases had leukemia (19.6%), 1 case had myelodysplastic syndrome with refractory anemia with excess blast(RAEB-T), and 1 case had Epstein-Barr virus(EBV) associated lymphoproliferative disease (borderline tumor stage). All the patients had a fever.A half of them suffered from hepatosplenomegaly and 7 patients(15.2%) had neurological symptoms.The common laboratory abnormalities included cytopenias, hemophagocytosis in bone marrow (81.8%, 36/44 cases), elevated serum ferritin (87.8%, 36/41 cases), and elevated sCD25 (100.0%, 15/15 cases), decreased nature killer(NK) activity (61.1%, 11/18 cases), and plasma EBV-DNA positive (57.9%). Four patients did not receive treatment, the rest were treated by several chemotherapy protocols including the HLH-94/2004 protocol.Five patients (10.8%) received the allogeneic hematopoietic stem cell transplantation, and 1 case received the splenectomy therapy.The mortality was 58.7%.Four heterozygous mutations of SH2D1A, UNC13D and PRF1 genes were found in 2 patients.@*Conclusions@#MAHS in children progresses rapidly, with poor prognosis, and it is often complicated with EBV infection.The children with MAHS may develop genetic defects similar to primary hemophagocytic syndrome.Nowadays, there is no standard treatment for MAHS, so the individualized treatment is to be explored.

Killer cell immunoglobulin-like receptor gene polymorphisms predispose susceptibility to Epstein-Barr virus associated hemophagocytic lymphohistiocytosis in Chinese children.

Epstein-Barr virus associated hemophagocytic lymphohistiocytosis (EBV-HLH) has a high mortality rate among children. The pathogenesis of, and underlying predisposing factors for, EBV-HLH are as yet unclear; however, natural killer cells may play a key role in progression of the disease. This study attempted to determine whether killer cell immunoglobulin-like receptor (KIR) gene polymorphisms are responsible for susceptibility to EBV-HLH. Of the 125 children with EBV infection studied, 59 had EBV-HLH and 66 patients had EBV associated infectious mononucleosis (IM) without HLH. The control group was 146 normal children without immune deficiency. KIR polymorphisms were determined by polymerase chain reaction with sequence-specific primers. KIR polymorphism data were analyzed using the X(2) test or Fisher's exact test. The overall observed carrier frequency (OF) of KIR2DS5 was significantly higher in EBV-HLH patients than in IM patients and normal controls (49.2% versus 31.8%, P = 0.048; 49.2% versus 31.5%, P = 0.018, respectively), and the odds ratios (95% confidence interval) were 2.071 (1.001-4.286) and 2.101(1.132-3.900) respectively. The OF of KIR3DS1 was significantly higher in the EBV-HLH patients than in the IM patients (47.4% versus 24.6%, P = 0.012), but not different from normal controls. In summary, KIR polymorphisms may be involved in the development of EBV-HLH, with KIR2DS5 promoting susceptibility to this disease. The obtained KIR data will enrich the understanding of genetic relationships among diseases associated with EBV infection in children.

Screening the PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK gene mutations in Chinese children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.

BACKGROUND: This study aimed to investigate the prevalence of mutations in the PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK in Chinese pediatric patients with EBV-HLH. METHODS: Sixty-seven pediatric patients diagnosed with EBV-HLH in Beijing Children's Hospital were recruited. Nucleotide sequences of all exons and their flanking intronic sequences of PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK were amplified by PCR followed by direct sequencing. RESULTS: Eight patients were identified with heterozygous, compound heterozygous, or homozygous mutations in PFR1, UNC13D, and XIAP. Three missense mutations (c.83G>A, c.503G>A, c.632C>T) were found in PRF1 of two males and two females. Compound heterozygous c.93C>G and c.1066C>T were found in PRF1 of a 2.5-year-old female. Four different mutations were found in UNC13D of two patients: compound nonsense heterozygous mutations c.766C>T and c.1215C>G were found in one male and two splicing mutations c.1596+1G>C and c.2709+1G>A were found in another male. A heterozygous mutation c.1099+2T>C in XIAP was found in a 4-year-old male. No detrimental mutations were identified in STX11, SH2D1A, or ITK. NK cell activity did not differ between the eight FHL patients and the remaining patients. There was no statistical difference in clinical features and laboratory data for these two subgroups with biallelic and heterozygous mutations. CONCLUSIONS: Seven novel mutations in PRF1, UNC13D, and XIAP were identified in EBV-HLH patients. Only a fraction of the Chinese children with EBV-HLH have genetic defects in PRF1, UNC13D, and XIAP. There were no gene mutations of PRF1/UNC13D/STX11/SH2D1A/XIAP/ITK in the majority of Chinese child patients with EBV-HLH.

Advances in hereditary research of primary hemophagocytic lymphohistiocytosis / 国际儿科学杂志

Hemophagocytic lymphohistiocytosis(HLH)is a life-threatening syndrome characterized by multiple organs infiltrations of lymphocytes and histiocytes with proliferation and hemophagocytic activity,and pancytopenia.HLH can be classified as either primary or secondary.Primary HLH includes familial HLH and immune deficiency syndromes associated HLH.Until now, familial HLH is classified into five types, whereas,immune deftciencv svndromes associated HLH is divided into Chediak-Higashi syndrome, GrisceUi syndrome 2,research of primary HLH. screening genetic defects and researches in functions of target genes and coding proteins, the effect of these genes and proteins in pathogenesis of HLH could be known further.

EFFECT OF CHLOROGENIC ACID ON GLUCOSE CONSUMPTION IN HepG2 CELLS PRETREATED WITH HIGH INSULIN AND HIGH OLEIC ACID / 营养学报

Objective To explore the modulation of chlorogenic acid (CGA) on glucose metabolism in HepG2 cells pretreated with high insulin and high oleic acid (OA). Methods Cultured HepG2 cells induced by high insulin and oleic acid for insulin resistance and steatosis respectively, were co-cultured with different concentrations of CGA (10,20,40,80 mg/L) for 24h. The morphological changes were observed and glucose consumptions of cells were measured by glucose oxidase method. Results Compared to control group, CGA could significantly increase glucose consumption of normal HepG2 cells and the dosedependent effect was noted between 10-40 mg/L(P