Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR

Severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia (XLA) are inborn errors of immune function that require prompt diagnosis and treatment to prevent life-threatening infections. The lack of functional T or B lymphocytes in these diseases serves as a diagnostic criterion and can be applied to neonatal screening. A robust triplex PCR method for quantitation of T-cell receptor excision circles (TRECs) and κ-deleting recombination excision circles (KRECs), using a single Guthrie card punch, was developed and validated in a cohort of 2560 anonymized newborn screening cards and in 49 original stored Guthrie cards from patients diagnosed with SCID, XLA, ataxia-telangiectasia, Nijmegen-breakage-syndrome, common variable immunodeficiency, immunoglobulin A deficiency, or X-linked hyper-IgM syndrome. Simultaneous measurement of TREC and KREC copy numbers in Guthrie card samples readily identified patients with SCID, XLA, ataxia-telangiectasia and Nijmegen-breakage-syndrome and thus facilitates effective newborn screening for severe immunodeficiency syndromes characterized by the absence of T or B cells.     

23例仅C3沉积的儿童原发性肾病的临床病理特征

目的:通过回顾性分析首都医科大学附属北京儿童医院肾组织病理免疫荧光仅有C3沉积(≥2+)的肾病患儿的临床及病理特点,以加深对儿童以C3沉积为主的原发性肾病的认识.方法:选取首都医科大学附属北京儿童医院肾活检病理结果仅补体C3沉积(≥2+),不伴免疫复合物沉积或仅有少许IgM沉积的原发性肾病患儿.收集患者临床、病理信息及肾功能、补体C3,C4水平等资料.同时记录治疗及转归.结果:病理提示仅C3沉积(≥2+)的原发性肾病患儿23例,包括急性链球菌感染后肾炎7例,无明确病因的肾炎综合征6例,肾炎型肾病综合征7例,反复发作性肉眼血尿3例.其中补体C3降低者20例.23例患儿中病理表现为毛细血管内增生性肾炎11例,局灶增生性肾炎1例,新月体肾炎1例,增生硬化或硬化性肾炎6例,膜增生性肾炎4例.免疫荧光C3强度2+9例,3+14例,内皮下、上皮下、系膜区均可见沉积.随访中大部分肾功能正常,6例患儿就诊即出现严重肾功能不全者,预后不佳.结论:以C3沉积为主的肾病患儿临床与病理表现多种多样,预后与病理改变有关.     

Impact of Comorbidity on Mortality Among Older Persons with Advanced Heart Failure

BACKGROUND  

Care for patients with advanced heart failure (HF) has traditionally focused on managing HF alone; however, little is known about the prevalence and contribution of comorbidity to mortality among this population. We compared the impact of comorbidity on mortality in older adults with HF with high mortality risk and those with lower mortality risk, as defined by presence or absence of a prior hospitalization for HF, respectively.     

NKG2C deletion is a risk factor of HIV infection

NK cell function is important in the immune response to HIV infection. NKG2C and NKG2A are activating and inhibitory NK cell receptors, respectively, and their only known ligand, HLA-E, demonstrates increased expression in HIV infection and presents at least one HIV-derived peptide. A variation in chromosome 12 exists in which the 16-kb section of DNA encompassing the nkg2c gene is completely absent. DNA samples of 433 HIV-1-infected patients and 280 controls were genotyped by PCR, and revealed an association of the absence variation with a higher risk of HIV infection, as well as faster progression and higher pretreatment viral loads (p<0.05, respectively). Surface NKG2C expression, analyzed by FACS, on the freshly isolated lymphocytes of 20 control and 19 HIV-infected donors revealed that NKG2C expression is genotype dependent in both populations: no NKG2C expression in the -/- groups, intermediate expression in the +/- groups, and highest expression in the +/+ groups. The comparison of NKG2C and NKG2A expression in HIV and control groups (+/- and +/+ included) indicates an increased NKG2C expression on HIV patient NK cells (p<0.05) and decreased inhibitory NKG2A expression on CD8 T cells (p<0.001), and both these effects are more striking in the +/+ genotype (p<0.005). Furthermore, a positive correlation was found between HIV viral load and the proportion of NKG2C(+) NK cells. The increased expression of NKG2C in HIV patients, in combination with the genetic association of the absence variation with an increased susceptibility to HIV infection, higher HIV viral set point, and a faster progression, indicate that NKG2C is important in the defense against HIV infection and progression.