Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation

Background Probiotics are widely studied both in the treatment and prevention of allergic diseases, but their mode of action is poorly known. Objective Our aim was to examine the effect of probiotic bacteria on in vivo cytokine, antibody, and inflammatory responses in allergy‐prone infants. Methods In a randomized double‐blind study, probiotic bacteria or placebo were given for 1 month before delivery to mothers and for 6 months to infants with a family history of allergy. Plasma samples were analysed for C‐reactive protein (CRP), total IgA and IgE, food‐specific IgA, IgG, and IgE, IL‐2, IL‐4, IL‐6, IL‐10, TNF‐α, and IFN‐γ. We analysed the associations of immunological and inflammatory parameters at age 6 months with probiotic treatment and allergic phenotype at 2 years. Results Infants receiving probiotic bacteria had higher plasma levels of CRP (P=0.008), total IgA (P=0.016), total IgE (P=0.047), and IL‐10 (P=0.002) than infants in the placebo group. Increased plasma CRP level at age 6 months was associated with a decreased risk of eczema [odds ratio (OR) 0.41 [95% confidence interval (CI) 0.17–0.99], P=0.046], and with a decreased risk of allergic disease [OR 0.38 (95% CI 0.16–0.87), P=0.023] at age 2 years, when adjusted with probiotic use. Conclusion The association of CRP with a decreased risk of eczema at 2 years of age in allergy‐prone children supports the view that chronic, low‐grade inflammation protects from eczema. Probiotic‐induced low‐grade inflammation was characterized by elevation of IgE, IgA, and IL‐10, the changes typically observed in helminth infection‐associated induction of regulatory mechanisms. The findings emphasize the role of chronic microbial exposure as an immune modulator protecting from allergy.     

《伤寒论》六经辨证在IgA肾病诊治中的指导价值

《伤寒论》六经辨证是在《黄帝内经》六经理论及脏象、经络两学说的基础上发展、完善而得来的,是中医的鼻祖。本文的主要目的是探讨《伤寒论》六经辨证在IgA肾病诊治中应用价值。IgA肾病又称为原发性肾小球疾病,在我国常见,其整个发病过程可视为从三阳经(太阳、阳明、少阳)转变为三阴经(太阴、少阴及厥阴)。IgA肾病在各经为病,脉症特点并不相同,因此IgA肾病采用六经辨证为指导,判断病情,能够有效防治IgA肾病,对临床具有重要的意义及价值。     

RTS,S/AS01E malaria vaccine induces IgA responses against CSP and vaccine-unrelated antigens in African children in the phase 3 trial

BackgroundThe evaluation of immune responses to RTS,S/AS01 has traditionally focused on immunoglobulin (Ig) G antibodies that are only moderately associated with protection. The role of other antibody isotypes that could also contribute to vaccine efficacy remains unclear. Here we investigated whether RTS,S/AS01_E elicits antigen-specific serum IgA antibodies to the vaccine and other malaria antigens, and we explored their association with protection.MethodsNinety-five children (age 5–17 months old at first vaccination) from the RTS,S/AS01_E phase 3 clinical trial who received 3 doses of RTS,S/AS01_E or a comparator vaccine were selected for IgA quantification 1 month post primary immunization. Two sites with different malaria transmission intensities (MTI) and clinical malaria cases and controls, were included. Measurements of IgA against different constructs of the circumsporozoite protein (CSP) vaccine antigen and 16 vaccine-unrelated Plasmodium falciparum antigens were performed using a quantitative suspension array assay.ResultsRTS,S vaccination induced a 1.2 to 2-fold increase in levels of serum/plasma IgA antibodies to all CSP constructs, which was not observed upon immunization with a comparator vaccine. The IgA response against 13 out of 16 vaccine-unrelated P. falciparum antigens also increased after vaccination, and levels were higher in recipients of RTS,S than in comparators. IgA levels to malaria antigens before vaccination were more elevated in the high MTI than the low MTI site. No statistically significant association of IgA with protection was found in exploratory analyses.ConclusionsRTS,S/AS01_E induces IgA responses in peripheral blood against CSP vaccine antigens and other P. falciparum vaccine-unrelated antigens, similar to what we previously showed for IgG responses. Collectively, data warrant further investigation of the potential contribution of vaccine-induced IgA responses to efficacy and any possible interplay, either synergistic or antagonistic, with protective IgG, as identifying mediators of protection by RTS,S/AS01_E immunization is necessary for the design of improved second-generation vaccines.Clinical trial registration: ClinicalTrials.gov: NCT008666191.     

Pathogenesis of idiopathic IgA nephropathy

Despite a prodigious amount of work on the physiology of IgA production in man, and many studies on the immunopathology of IgA nephropathy, ranging from the immunogenetics to the immune response to chemical characteristics of the IgA, we are hardly any nearer to defining the pathogenesis of this disease. One of the main changes in our understanding has been to recognise that the bone marrow, now known to produce normally one-third of the body's IgA, overproduces this immunoglobulin in IgA nephropathy. This alters the previous notion that IgA nephropathy was due simply to IgA production in the mucosa, although a mucosal component is not excluded. Certain characteristics of the IgA in the diseased kidney and the circulation have been defined: it is of subclass IgA1 and has a higher proportion of light chains and negative charge than in normal subjects. The specificities of the IgA, either in the kidney or in complexes, have not helped to clarify the pathogenesis. They have been found for a wide range of endogenous and exogenous antigens, suggesting that the antibody activity represents polyclonal B cell activation. These findings have not helped to confirm the prevailing theory that IgA nephropathy is an immune complex disease. Other theories put forward are that IgA nephropathy is an autoimmune disease, glomerular components or IgA itself being among the candidate antigens, or that there is primary dysregulation of the IgA immune system. At this stage of development in our understanding of this common nephropathy, it is important to guard against the assumption that idiopathic IgA nephropathy is one disease and is the result of a single pathogenetic mechanism.     

IgA肾病患者的扁桃体免疫组织化学观察

目的：了解ＩｇＡ肾病（ＩｇＡ－Ｎ）与扁桃体免疫异常的关系。方法：经肾穿刺活检确诊为ＩｇＡ－Ｎ３１例,以慢性扁桃体炎１６例作对照,扁桃体切除术后运用ＡＢＣ方法对扁桃体组织进行免疫组化标记。结果：两组扁桃体在ＩｇＡ、ＩｇＧ的表达上存在明显的区别,ＩｇＡ－Ｎ患者的扁桃体组织内产生ＩｇＡ的淋巴细胞数显著增加,结论：ＩｇＡ－Ｎ患者存在着扁桃体免疫异常,切除扁桃可预防抗原入浸,消除扁桃体来源的ＩｇＡ,减少循环中的ＩｇＡ免疫复合物形成,进一步使肾小球基底膜区的ＩｇＡ免疫复合物沉积减少。     

Modified sternal elevation for children with pectus excavatum

Objective To investigate the relationship between intestinal mucus IgA content and mucus barrier function after surface burns. Methods Detection of IgA content in mucus was performed by enzyme linked immunosorbent assay (ELISA) at different time points after burns.Bacterial adherence to cultured epithelial cells (IEC-6) in vitro using E.coli was assessed for each group. Results The intestinal mucus barrier function declined, parallel to a decrease in IgA content after surface burn in mice.In the normal control group, mucus IgA content was 2.32 Dλ, and 2.51, 1.76, 1.49, 1.06 Dλ at 0.5 h, 1 h, 6 h and 24 h after burn, respectively.Bacterial adherence rate was 0.53 in control group, and 0.46, 0.69, 0.58, 0.81 at 0.5 h, 1 h, 6 h, 24 h after burn, respectively. Conclusion The decrease of intestinal mucus IgA contents is one of the reasons why intestinal mucus barrier function declines after burns.     

Polymorphisms of TAP, LMP and HLA-DM genes in the Chinese

Ｔｒａｎｓｐｏｒｔｅｒａｓｓｏｃｉａｔｅｄｗｉｔｈａｎｔｉｇｅｎｐｒｏｃｅｓｓｉｎｇ(ＴＡＰ),ｌｏｗｍｏｌｅｃｕｌａｒｗｅｉｇｈｔｐｒｏｔｅａｓｏｍｅ(ＬＭＰ)ａｎｄＨＬＡＤＭａｒｅＭＨＣｃｌａｓｓⅡｌｉｋｅｇｅｎｅｓｗｈｉｃｈｈａｖｅｂｅｅｎｍａｐｐｅｄｂｅｔｗｅｅｎＨＬＡＤＰａｎｄＨＬＡＤＯｌｏｃｉｉｎｔｈｅｃｌａｓｓⅡｒｅｇｉｏｎｏｆｔｈｅｈｕｍａｎｍａｊｏｒｈｉｓｔｏｃｏｍｐａｔｉｂｉｌｉｔｙｃｏｍｐｌｅｘ1　ＴｈｅｓｅｇｅｎｅｓｄｉｆｆｅｒｆｒｏｍｔｈｅｃｌａｓｓｉｃｃｌａｓｓⅡｇｅｎｅｓ…     

Influence of α-tocopherol over the time course of experimental IgA nephropathy

 The present study investigated the pathogenesis and the time course of kidney injury in experimental IgA nephropathy. In order to determine an appropriate period in the course of experimental IgA nephropathy to study renal injury and repair, we examined proteinuria and IgA deposition in the renal mesangium after 4, 8, and 16 weeks of mucosal challenge by bovine gamma globulins (BGG) provided in the drinking water. The hallmark of IgA deposition in the mesangium was present after 4 weeks and 8 weeks of BGG inoculation, but by 16 weeks, the mesangial IgA deposition had resolved. In addition, we confirmed our previous report on the beneficial effects of α-tocopherol in reducing proteinuria in IgA nephropathy at 8 weeks, and extended this observation to investigate the effects of dietary supplementation of α-tocopherol at both 4 weeks and 16 weeks. Proteinuria resolved spontaneously at 16 weeks. There is oxidative stress, as suggested by the elevation in plasma and renal malondialdehyde content, and increased fibrogenic cytokine message, as suggested by elevated transforming growth factor β1 mRNA. These increases were clearly blunted by α-tocopherol at both 4 weeks and 8 weeks. Treatment with α-tocopherol was associated with a significant reduction in the severity of proteinuria. Thus, our data suggest that the period between 4 and 8 weeks of BGG vaccination could be relevant in designing an appropriate model to study the molecular biology of the pathogenesis of renal injury and the effects of treatment. The 16-week model may be useful in exploring gene expression involved with spontaneous resolution. Received: 17 February 1998 / Revised: 2 June 1998 / Accepted: 3 June 1998     

Leucoéncephalopathie multifocale progressive

Summary A young woman presented a mixed congenital and familial immunodeficiency syndrome consisting in an absence of IgA and lowered levels of IgG and IgM, with a defect in cellular immunity. She had a mild malabsorption syndrome with slight alterations of the jejunal mucosa. Non-caseating tuberculoid granulomata were found in skin lesions, in lymph nodes and in the spleen. At age 27 the patient died of a neurological disease of 4 months duration. Autopsy revealed a very widespread demyelinating process involving mainly the right cerebellar hemisphere but also most of the pons and left cerebellum, with the typical morphologic characters of PML. In the hemispheres lesions were limited to microscopical microglial nodules with discrete demyelination. A review of 86 published cases of PML revealed 9 other cases in which lesions showed a strong predilection for the subtentorial territories. This sampling allows for the assumption that some 11% of the cases of PML have this particular lesion distribution. Other pertinent features of this case are briefly discussed.