BACKGROUND There are few cases of pulmonary granulomatous changes secondary to primary biliary cirrhosis(PBC).No case of granulomatous lung disease secondary to PBC misdiagnosed as lung cancer had been reported.CASE S...BACKGROUND There are few cases of pulmonary granulomatous changes secondary to primary biliary cirrhosis(PBC).No case of granulomatous lung disease secondary to PBC misdiagnosed as lung cancer had been reported.CASE SUMMARY A middle-aged woman presented with lung nodules and was misdiagnosed with lung cancer by positron emission tomography/computed tomography.She underwent left lobectomy,and the pathology of the nodules showed granulomatous inflammation,which was then treated with antibiotics.However,a new nodule appeared.Further investigation with lung biopsy and liver serology led to the diagnosis of PBC,and chest computed tomography indicated significant reduction in the pulmonary nodule by treatment with methylprednisolone and ursodeoxycholic acid.CONCLUSION Diagnosis of pulmonary nodules requires integrating various clinical data to avoid unnecessary pulmonary lobectomy.展开更多
Objective:To investigate granulomatous inflammation etiology based on clinical history and ancillary tests.Methods:Children aged<18 years with biopsy proven granulomatous lesions in any tissue specimens between Jan...Objective:To investigate granulomatous inflammation etiology based on clinical history and ancillary tests.Methods:Children aged<18 years with biopsy proven granulomatous lesions in any tissue specimens between January 2014 and January 2022 were included in the study.The diagnosis was based on the results of immunohistochemical staining,molecular tests,culture,serology,radiological and other auxiliary laboratory tests.Diagnoses were categorized into infectious and noninfectious causes.Results:In total,174 patients with granulomatosis inflammation confirmed by histopathology were analyzed.Approximately 59.2%patients were males,and the median age was 4.48(IQR 2.36-6.39)years(range:16 months-18 years).The tissues/organs that were most commonly biopsied were lymph node,bone,skin,and lung(51.1%,17.8%,9.2%,and 5.7%,respectively).Infectious and non-infectious causes were identified in 73.0%and 12.6%patients,respectively,in terms of granulomatosis inflammation etiology;however,no cause was identified in 14.4%patients.The most common infectious cause was tuberculosis(in 51.7%patients),followed by toxoplasmosis,aspergillosis,mucormycosis,leishmaniasis,and cat-scratch disease(in 8.6%,5.7%,1.7%,1.7%,and 1.1%patients,respectively).The common non-infectious cause was chronic granulomatous disease.Histopathological evaluation revealed granulomatosis inflammation in 33.3%patients,necrotizing granulomatosis inflammation in 30.5%patients,and caseating granulomatosis inflammation in 12.1%patients.When the pathology results of patients with and without tuberculosis were compared,the incidence of caseating granulomatosis inflammation(P=0.003)and necrotizing granulomatosis inflammation(P=0.005)was higher in patients with tuberculosis.Conclusions:Chronic granulomatous disease is the most common non-infectious cause in children.Moreover,primary or secondary immune deficiencies may cause granulomatosis inflammation,especially in pediatric patients.展开更多
BACKGROUND Chronic granulomatous disease(CGD)characterized by recurrent and severe bacterial and fungal infections is most common in childhood.CASE SUMMARY We reported a 24-d-old male infant who developed gastrointest...BACKGROUND Chronic granulomatous disease(CGD)characterized by recurrent and severe bacterial and fungal infections is most common in childhood.CASE SUMMARY We reported a 24-d-old male infant who developed gastrointestinal symptoms as the first sign of CGD.CONCLUSION Gastrointestinal symptoms representing the first sign of CGD are very rare,and prompt diagnosis and treatment with broad-spectrum antibiotics were of crucial importance.展开更多
Chronic granulomatous disease(CGD)is an inherited defect of phagocyte function due to defective NADPH oxidase.Patients with CGD are not able to effectively clear the infections because of the defect in the phagocyte p...Chronic granulomatous disease(CGD)is an inherited defect of phagocyte function due to defective NADPH oxidase.Patients with CGD are not able to effectively clear the infections because of the defect in the phagocyte production of oxygen free radicals and are prone to recurrent bacterial and fungal infections.Inflammatory complications are also noted in CGD such as colitis,non-infective granulomas causing gastrointestinal or urinary tract obstruction,hemophagocytic lymphohistiocytosis,and arthritis.Studies on toll-like receptor pathways and neutrophil extracellular traps in CGD have shed light on the role of NADPH oxidase in the innate immunity and pathogenesis of infections in CGD.Some reports also indicate a reduction of memory B cells and defective production of functional antibodies in CGD.Though the exact mechanisms for non-infective inflammatory complications in CGD are not yet clear,studies on efferocytosis and defective autophagy with inflammasome activation have made a substantial contribution to our understanding of the pathogenesis of inflammation in CGD.We also discuss the clinical and molecular features of p40phox defects and a newer genetic defect,EROS.Clinical phenotypes of X-linked carriers of CYBB are also discussed.展开更多
In past two decades the gene therapy using genetic modified autologous hematopoietic stem cells(HSCs)transduced with the viral vector has become a promising alternative option for treating primary immunodeficiency dis...In past two decades the gene therapy using genetic modified autologous hematopoietic stem cells(HSCs)transduced with the viral vector has become a promising alternative option for treating primary immunodeficiency diseases(PIDs).Despite of some pitfalls at early stage clinical trials,the field of gene therapy has advanced significantly in the last decade with improvements in viral vector safety,preparatory regime for manufacturing high quality virus,automated CD34 cell purification.Hence,the overall outcome from the clinical trials for the different PIDs has been very encouraging.In addition to the viral vector based gene therapy,the recent fast moving forward developments in genome editing using engineered nucleases in HSCs has provided a new promising platform for the treatment of PIDs.This review provides an overall outcome and progress in gene therapy clinical trials for SCID-X,ADA-SCID,WAS,X-CGD,and the recent developments in genome editing technology applied in HSCs for developing potential therapy,particular in the key studies for PIDs.展开更多
基金The Special Health Project of the Department of Finance of Jilin Province,China,No.2020SCZT023 and No.3D5177713429.
文摘BACKGROUND There are few cases of pulmonary granulomatous changes secondary to primary biliary cirrhosis(PBC).No case of granulomatous lung disease secondary to PBC misdiagnosed as lung cancer had been reported.CASE SUMMARY A middle-aged woman presented with lung nodules and was misdiagnosed with lung cancer by positron emission tomography/computed tomography.She underwent left lobectomy,and the pathology of the nodules showed granulomatous inflammation,which was then treated with antibiotics.However,a new nodule appeared.Further investigation with lung biopsy and liver serology led to the diagnosis of PBC,and chest computed tomography indicated significant reduction in the pulmonary nodule by treatment with methylprednisolone and ursodeoxycholic acid.CONCLUSION Diagnosis of pulmonary nodules requires integrating various clinical data to avoid unnecessary pulmonary lobectomy.
文摘Objective:To investigate granulomatous inflammation etiology based on clinical history and ancillary tests.Methods:Children aged<18 years with biopsy proven granulomatous lesions in any tissue specimens between January 2014 and January 2022 were included in the study.The diagnosis was based on the results of immunohistochemical staining,molecular tests,culture,serology,radiological and other auxiliary laboratory tests.Diagnoses were categorized into infectious and noninfectious causes.Results:In total,174 patients with granulomatosis inflammation confirmed by histopathology were analyzed.Approximately 59.2%patients were males,and the median age was 4.48(IQR 2.36-6.39)years(range:16 months-18 years).The tissues/organs that were most commonly biopsied were lymph node,bone,skin,and lung(51.1%,17.8%,9.2%,and 5.7%,respectively).Infectious and non-infectious causes were identified in 73.0%and 12.6%patients,respectively,in terms of granulomatosis inflammation etiology;however,no cause was identified in 14.4%patients.The most common infectious cause was tuberculosis(in 51.7%patients),followed by toxoplasmosis,aspergillosis,mucormycosis,leishmaniasis,and cat-scratch disease(in 8.6%,5.7%,1.7%,1.7%,and 1.1%patients,respectively).The common non-infectious cause was chronic granulomatous disease.Histopathological evaluation revealed granulomatosis inflammation in 33.3%patients,necrotizing granulomatosis inflammation in 30.5%patients,and caseating granulomatosis inflammation in 12.1%patients.When the pathology results of patients with and without tuberculosis were compared,the incidence of caseating granulomatosis inflammation(P=0.003)and necrotizing granulomatosis inflammation(P=0.005)was higher in patients with tuberculosis.Conclusions:Chronic granulomatous disease is the most common non-infectious cause in children.Moreover,primary or secondary immune deficiencies may cause granulomatosis inflammation,especially in pediatric patients.
文摘BACKGROUND Chronic granulomatous disease(CGD)characterized by recurrent and severe bacterial and fungal infections is most common in childhood.CASE SUMMARY We reported a 24-d-old male infant who developed gastrointestinal symptoms as the first sign of CGD.CONCLUSION Gastrointestinal symptoms representing the first sign of CGD are very rare,and prompt diagnosis and treatment with broad-spectrum antibiotics were of crucial importance.
文摘Chronic granulomatous disease(CGD)is an inherited defect of phagocyte function due to defective NADPH oxidase.Patients with CGD are not able to effectively clear the infections because of the defect in the phagocyte production of oxygen free radicals and are prone to recurrent bacterial and fungal infections.Inflammatory complications are also noted in CGD such as colitis,non-infective granulomas causing gastrointestinal or urinary tract obstruction,hemophagocytic lymphohistiocytosis,and arthritis.Studies on toll-like receptor pathways and neutrophil extracellular traps in CGD have shed light on the role of NADPH oxidase in the innate immunity and pathogenesis of infections in CGD.Some reports also indicate a reduction of memory B cells and defective production of functional antibodies in CGD.Though the exact mechanisms for non-infective inflammatory complications in CGD are not yet clear,studies on efferocytosis and defective autophagy with inflammasome activation have made a substantial contribution to our understanding of the pathogenesis of inflammation in CGD.We also discuss the clinical and molecular features of p40phox defects and a newer genetic defect,EROS.Clinical phenotypes of X-linked carriers of CYBB are also discussed.
基金We thank Dr Alessia Cavazza for helping in the manuscript correction.FZ is supported by the Wellcome Trust(104807/Z/14/Z)ZYZ is supported by National Natural Science Foundation of China(NO.81202316)+1 种基金Foundation from Children’s Hospital of Chongqing Medical University.AJT is supported by both the Wellcome Trust(104807/Z/14/Z)by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London.
文摘In past two decades the gene therapy using genetic modified autologous hematopoietic stem cells(HSCs)transduced with the viral vector has become a promising alternative option for treating primary immunodeficiency diseases(PIDs).Despite of some pitfalls at early stage clinical trials,the field of gene therapy has advanced significantly in the last decade with improvements in viral vector safety,preparatory regime for manufacturing high quality virus,automated CD34 cell purification.Hence,the overall outcome from the clinical trials for the different PIDs has been very encouraging.In addition to the viral vector based gene therapy,the recent fast moving forward developments in genome editing using engineered nucleases in HSCs has provided a new promising platform for the treatment of PIDs.This review provides an overall outcome and progress in gene therapy clinical trials for SCID-X,ADA-SCID,WAS,X-CGD,and the recent developments in genome editing technology applied in HSCs for developing potential therapy,particular in the key studies for PIDs.