BACKGROUND In paediatric patients with complicated nephrotic syndrome(NS), rituximab(RTX) administration can induce persistent IgG hypogammaglobulinemia among subjects showing low basal immunoglobulin G(IgG) levels.AI...BACKGROUND In paediatric patients with complicated nephrotic syndrome(NS), rituximab(RTX) administration can induce persistent IgG hypogammaglobulinemia among subjects showing low basal immunoglobulin G(IgG) levels.AIM To evaluate the effect of RTX on IgG levels and infections in patients with complicated NS and normal basal IgG levels.METHODS We consecutively enrolled all patients with complicated NS and normal basal IgG levels undergoing the first RTX infusion from January 2008 to January 2016. Basal IgG levels were dosed after 6 wk of absent proteinuria and with a maximal interval of 3 mo before RTX infusion. The primary outcome was the onset of IgG hypogammaglobulinemia during the follow-up according to the IgG normal values for age [mean ± standard deviation(SD)].RESULTS We enrolled 20 patients with mean age at NS diagnosis of 4.2 ± 3.3 years. The mean age at the first RTX infusion was 10.9 ± 3.5 years. Eleven out of twenty patients(55%) developed IgG hypogammaglobulinemia. None of these patients showed severe or recurrent infections. Only one patient suffered from recurrent acute otitis media and underwent substitutive IgG infusion. Three patients undergoing only the two "starting doses" experienced normalization of IgG levels. Using Kaplan-Meier analysis, the cumulative proportion of patients free of IgG hypogammaglobulinemia was 57.8% after the first RTX dose, 51.5% after the third dose, 44.1% after the fourth dose, and 35.5% after the fifth dose.CONCLUSION RTX can induce IgG hypogammaglobulinemia in patients with pre-RTX IgG normal values. None of the treated patients showed severe infections.展开更多
BACKGROUND Lymphangioma is a benign lesion that rarely involves the gastrointestinal tract,especially in adults.Small bowel lymphangioma is a rare cause of gastrointestinal bleeding.Here,we report a case of an adult d...BACKGROUND Lymphangioma is a benign lesion that rarely involves the gastrointestinal tract,especially in adults.Small bowel lymphangioma is a rare cause of gastrointestinal bleeding.Here,we report a case of an adult diagnosed with jejunal lymphangioma presenting with melena,anemia and hypogammaglobulinemia.We also summarize and analyze all 23 reported cases from 1961 to 2019,and propose an algorithm for identification and management of small bowel lymphangioma.CASE SUMMARY A case of a 29-year-old woman presented with persistent melena and irondeficiency anemia,accompanied by hypogammaglobulinemia.No lesions were found in the initial workup with esophagogastroduodenoscopy,colonoscopy and computed tomography(CT)enterography.Ultimately,capsule endoscopy and double-balloon enteroscopy revealed a 3 cm×2 cm primary lesion with intensive white lymphatic dilatatory changes and visible fresh blood stains,accompanied by a small satellite lesion.The patient underwent complete surgical resection of these lesions,and histopathological examination confirmed a diagnosis of cavernous lymphangioma of the jejunum.The patient showed no evidence of disease at the time of this report.CONCLUSION We recommend CT,capsule endoscopy and enteroscopy to identify the lesions of lymphangioma.Laparoscopic surgery with histological diagnosis is an ideal curative method.展开更多
A Pleural mass biopsy was performed showing an invasive thymoma. Computed tomography (CT) scan of the chest performed on admission revealed a left sided pleural mass, anterior mediastinal mass, lymphadenopathy and per...A Pleural mass biopsy was performed showing an invasive thymoma. Computed tomography (CT) scan of the chest performed on admission revealed a left sided pleural mass, anterior mediastinal mass, lymphadenopathy and pericardial effusion. Pleural mass biopsy showed an invasive thymoma. Due to her clinical presentation, a complete work-up was performed revealing paraneoplastic systemic lupus erythematous (SLE), myasthenia gravis (MG) and hypogammaglobulinemia. We reviewed the literature regarding thymoma and its relationship with paraneoplastic SLE, MG and hypogammaglobulinemia.展开更多
Background Hypogammaglobulinemia is common in infant humoral immunodeficiencies and has complicated causes and outcomes. We aimed to determine the clinical manifestations, immunological changes and outcomes of Shangha...Background Hypogammaglobulinemia is common in infant humoral immunodeficiencies and has complicated causes and outcomes. We aimed to determine the clinical manifestations, immunological changes and outcomes of Shanghai infants with hypogammaglobulinemia. Methods Patients under 2 years old, having one or more warning signs of primary immunodeficiency disorders, serum immunoglobulin levels below the lower limit of reference range per age, and with normal numbers for lymphocyte subsets were analyzed and followed up for 2 to 3 years. Results A total of 91 children （male-to-female ratio： 2.25： 1） participated in the study. Initial clinical presentation was recurrent upper respiratory tract infection （46%）, invasive infection （3%）, atopic disease （32%）. IgA reduction （77%） was prevalent; 34% patients had more than one isotype reduced. During follow-up, 51 of 62 patients （82.25%） had immunoglobulins normalized at the age between 12-48 months; these were diagnosed as transient hypogammaglobulinemia of infancy （THI）. Long-term follow-up may reveal a diagnosis for the remaining 11 infants with persistent lower Jmmunoglobulin levels, who did not have antibody titers measured. Earlier onset was correlated with higher rates of normalization. More patients were diagnosed with isolated hypogammaglobulinemia in 2006 compared with the previous 4 years （2002-2005）. Conclusions The awareness of immunodeficiency among pediatricians has been greatly improved. Recurrent otitis media was not a major infection in our patients. THI is a relatively common condition associated with infant hypogammaglobulinemia. In the absence of specific antibody titers, the diagnosis of THI can be confirmed retrospectively with Ig levels normalized in follow-up visits. Therefore, long-term follow-up and frequent re-evaluation of these patients are necessary to distinguish them from true primary immunodeficiency.展开更多
目的:探讨低丙种球蛋白血症与弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)患者的临床特征及其与预后的关系。方法:回顾性分析73例初治DLBCL患者治疗前血清丙种球蛋白水平,分析其与患者临床病理特征及预后的关系。根据丙种...目的:探讨低丙种球蛋白血症与弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)患者的临床特征及其与预后的关系。方法:回顾性分析73例初治DLBCL患者治疗前血清丙种球蛋白水平,分析其与患者临床病理特征及预后的关系。根据丙种球蛋白水平,将患者分为低丙种球蛋白组(15例)和正常/高丙种球蛋白组(58例)。比较2组患者临床病理特征、总生存期和疾病无进展生存期的差异,并使用Cox比例风险回归模型分析患者预后的独立危险因素。结果:在低丙种球蛋白组DLBCL患者中,高IPI评分、Ann Arbor分期(Ⅲ~Ⅳ)、β2微球蛋白水平高于正常上限、血清乳酸脱氢酶水平高于正常上限以及B症状患者的比例显著高于正常/高丙种球蛋白组(P<0.05)。低丙种球蛋白组DLBCL患者的总生存期和疾病无进展生存期更短(P<0.05)。Cox回归分析发现,高IPI评分和低丙种球蛋白是DLBCL患者预后的独立危险因素(P<0.05)。结论:初治DLBCL患者的丙种球蛋白水平与临床病理特征存在一定的相关性,低丙种球蛋白是远期总生存期和疾病无进展生存期缩短的独立危险因素,值得临床关注。展开更多
Immunodeficiency,centromeric instability,and facial anomalies(ICF)syndrome is a rare autosomal recessive disorder characterized by DNA hypomethylation and antibody deficiency.It is caused by mutations in DNMT3B,ZBTB24...Immunodeficiency,centromeric instability,and facial anomalies(ICF)syndrome is a rare autosomal recessive disorder characterized by DNA hypomethylation and antibody deficiency.It is caused by mutations in DNMT3B,ZBTB24,CDCA7,or HELLS.While progress has been made in elucidating the roles of these genes in regulating DNA methylation,little is known about the pathogenesis of the life-threatening hypogammaglobulinemia phenotype.Here,we show that mice deficient in Zbtb24 in the hematopoietic lineage recapitulate the major clinical features of patients with ICF syndrome.Specifically,Vav-Cre-mediated ablation of Zbtb24 does not affect lymphocyte development but results in reduced plasma cells and low levels of IgM,IgG1,and IgA.Zbtb24-deficient mice are hyper and hypo-responsive to T-dependent and T-independent type 2 antigens,respectively,and marginal zone B-cell activation is impaired.Mechanistically,Zbtb24-deficient B cells show severe loss of DNA methylation in the promoter region of Il5ra(interleukin-5 receptor subunit alpha),and Il5ra derepression leads to elevated CD19 phosphorylation.Heterozygous disruption of Cd19 can revert the hypogammaglobulinemia phenotype of Zbtb24-deficient mice.Our results suggest the potential role of enhanced CD19 activity in immunodeficiency in ICF syndrome.展开更多
To the Editor:Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropa...To the Editor:Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia,hypoalbuminemia,and hypogammaglobulinemia.展开更多
文摘BACKGROUND In paediatric patients with complicated nephrotic syndrome(NS), rituximab(RTX) administration can induce persistent IgG hypogammaglobulinemia among subjects showing low basal immunoglobulin G(IgG) levels.AIM To evaluate the effect of RTX on IgG levels and infections in patients with complicated NS and normal basal IgG levels.METHODS We consecutively enrolled all patients with complicated NS and normal basal IgG levels undergoing the first RTX infusion from January 2008 to January 2016. Basal IgG levels were dosed after 6 wk of absent proteinuria and with a maximal interval of 3 mo before RTX infusion. The primary outcome was the onset of IgG hypogammaglobulinemia during the follow-up according to the IgG normal values for age [mean ± standard deviation(SD)].RESULTS We enrolled 20 patients with mean age at NS diagnosis of 4.2 ± 3.3 years. The mean age at the first RTX infusion was 10.9 ± 3.5 years. Eleven out of twenty patients(55%) developed IgG hypogammaglobulinemia. None of these patients showed severe or recurrent infections. Only one patient suffered from recurrent acute otitis media and underwent substitutive IgG infusion. Three patients undergoing only the two "starting doses" experienced normalization of IgG levels. Using Kaplan-Meier analysis, the cumulative proportion of patients free of IgG hypogammaglobulinemia was 57.8% after the first RTX dose, 51.5% after the third dose, 44.1% after the fourth dose, and 35.5% after the fifth dose.CONCLUSION RTX can induce IgG hypogammaglobulinemia in patients with pre-RTX IgG normal values. None of the treated patients showed severe infections.
基金Supported by the General Program of Natural Science Foundation of Beijing Municipality,No.7192172
文摘BACKGROUND Lymphangioma is a benign lesion that rarely involves the gastrointestinal tract,especially in adults.Small bowel lymphangioma is a rare cause of gastrointestinal bleeding.Here,we report a case of an adult diagnosed with jejunal lymphangioma presenting with melena,anemia and hypogammaglobulinemia.We also summarize and analyze all 23 reported cases from 1961 to 2019,and propose an algorithm for identification and management of small bowel lymphangioma.CASE SUMMARY A case of a 29-year-old woman presented with persistent melena and irondeficiency anemia,accompanied by hypogammaglobulinemia.No lesions were found in the initial workup with esophagogastroduodenoscopy,colonoscopy and computed tomography(CT)enterography.Ultimately,capsule endoscopy and double-balloon enteroscopy revealed a 3 cm×2 cm primary lesion with intensive white lymphatic dilatatory changes and visible fresh blood stains,accompanied by a small satellite lesion.The patient underwent complete surgical resection of these lesions,and histopathological examination confirmed a diagnosis of cavernous lymphangioma of the jejunum.The patient showed no evidence of disease at the time of this report.CONCLUSION We recommend CT,capsule endoscopy and enteroscopy to identify the lesions of lymphangioma.Laparoscopic surgery with histological diagnosis is an ideal curative method.
文摘A Pleural mass biopsy was performed showing an invasive thymoma. Computed tomography (CT) scan of the chest performed on admission revealed a left sided pleural mass, anterior mediastinal mass, lymphadenopathy and pericardial effusion. Pleural mass biopsy showed an invasive thymoma. Due to her clinical presentation, a complete work-up was performed revealing paraneoplastic systemic lupus erythematous (SLE), myasthenia gravis (MG) and hypogammaglobulinemia. We reviewed the literature regarding thymoma and its relationship with paraneoplastic SLE, MG and hypogammaglobulinemia.
文摘Background Hypogammaglobulinemia is common in infant humoral immunodeficiencies and has complicated causes and outcomes. We aimed to determine the clinical manifestations, immunological changes and outcomes of Shanghai infants with hypogammaglobulinemia. Methods Patients under 2 years old, having one or more warning signs of primary immunodeficiency disorders, serum immunoglobulin levels below the lower limit of reference range per age, and with normal numbers for lymphocyte subsets were analyzed and followed up for 2 to 3 years. Results A total of 91 children （male-to-female ratio： 2.25： 1） participated in the study. Initial clinical presentation was recurrent upper respiratory tract infection （46%）, invasive infection （3%）, atopic disease （32%）. IgA reduction （77%） was prevalent; 34% patients had more than one isotype reduced. During follow-up, 51 of 62 patients （82.25%） had immunoglobulins normalized at the age between 12-48 months; these were diagnosed as transient hypogammaglobulinemia of infancy （THI）. Long-term follow-up may reveal a diagnosis for the remaining 11 infants with persistent lower Jmmunoglobulin levels, who did not have antibody titers measured. Earlier onset was correlated with higher rates of normalization. More patients were diagnosed with isolated hypogammaglobulinemia in 2006 compared with the previous 4 years （2002-2005）. Conclusions The awareness of immunodeficiency among pediatricians has been greatly improved. Recurrent otitis media was not a major infection in our patients. THI is a relatively common condition associated with infant hypogammaglobulinemia. In the absence of specific antibody titers, the diagnosis of THI can be confirmed retrospectively with Ig levels normalized in follow-up visits. Therefore, long-term follow-up and frequent re-evaluation of these patients are necessary to distinguish them from true primary immunodeficiency.
文摘目的:探讨低丙种球蛋白血症与弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)患者的临床特征及其与预后的关系。方法:回顾性分析73例初治DLBCL患者治疗前血清丙种球蛋白水平,分析其与患者临床病理特征及预后的关系。根据丙种球蛋白水平,将患者分为低丙种球蛋白组(15例)和正常/高丙种球蛋白组(58例)。比较2组患者临床病理特征、总生存期和疾病无进展生存期的差异,并使用Cox比例风险回归模型分析患者预后的独立危险因素。结果:在低丙种球蛋白组DLBCL患者中,高IPI评分、Ann Arbor分期(Ⅲ~Ⅳ)、β2微球蛋白水平高于正常上限、血清乳酸脱氢酶水平高于正常上限以及B症状患者的比例显著高于正常/高丙种球蛋白组(P<0.05)。低丙种球蛋白组DLBCL患者的总生存期和疾病无进展生存期更短(P<0.05)。Cox回归分析发现,高IPI评分和低丙种球蛋白是DLBCL患者预后的独立危险因素(P<0.05)。结论:初治DLBCL患者的丙种球蛋白水平与临床病理特征存在一定的相关性,低丙种球蛋白是远期总生存期和疾病无进展生存期缩短的独立危险因素,值得临床关注。
基金supported by a grant(1R01AI12140301A1)from the National Institutes of Health(NIH)in the USA.
文摘Immunodeficiency,centromeric instability,and facial anomalies(ICF)syndrome is a rare autosomal recessive disorder characterized by DNA hypomethylation and antibody deficiency.It is caused by mutations in DNMT3B,ZBTB24,CDCA7,or HELLS.While progress has been made in elucidating the roles of these genes in regulating DNA methylation,little is known about the pathogenesis of the life-threatening hypogammaglobulinemia phenotype.Here,we show that mice deficient in Zbtb24 in the hematopoietic lineage recapitulate the major clinical features of patients with ICF syndrome.Specifically,Vav-Cre-mediated ablation of Zbtb24 does not affect lymphocyte development but results in reduced plasma cells and low levels of IgM,IgG1,and IgA.Zbtb24-deficient mice are hyper and hypo-responsive to T-dependent and T-independent type 2 antigens,respectively,and marginal zone B-cell activation is impaired.Mechanistically,Zbtb24-deficient B cells show severe loss of DNA methylation in the promoter region of Il5ra(interleukin-5 receptor subunit alpha),and Il5ra derepression leads to elevated CD19 phosphorylation.Heterozygous disruption of Cd19 can revert the hypogammaglobulinemia phenotype of Zbtb24-deficient mice.Our results suggest the potential role of enhanced CD19 activity in immunodeficiency in ICF syndrome.
文摘To the Editor:Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia,hypoalbuminemia,and hypogammaglobulinemia.
