Properties of circulating IgA molecules in Henoch-Schonlein purpura nephritis with focus on neutrophil cytoplasmic antigen IgA binding (IgA-ANCA): new insight into a debated issue

Background: The presence and the pathogenetic role of circulating IgA reacting with neutrophil cytoplasmic antigens (IgA-ANCA) in patients with Henoch-Schonlein purpura (HSP) is still debated. This study was aimed to investigate some characteristics of serum IgA and macromolecular IgA in HSP patients, focusing on IgA-ANCA. Methods: Eighty-seven HSP patients with biopsy proved renal involvement (51 adults and 36 children) enrolled in a multicentre study of the Italian Group of Immunopathology were investigated. Results: Significantly high levels of IgA immune complexes were found in both adults (P <0.05) and children (P <0.01), while the binding of IgA to jacalin, was significantly low in children with HSP (P <0.01) only. Two series of ELISA were done for IgA-ANCA, in two different laboratories. Increased binding to PMN crude extracts (P <0.01) without any modification in IgA binding to proteinase 3 was found by either specific ELISA. Conversely, the binding of IgA to myeloperoxidase (MPO) was found to be significantly (P <0.05) increased with positive values in 25% of patients by one assay only. Three of four sera with positive IgA-MPO ANCA exhibited binding in Western-blot studies with the MPO preparation used in ELISA to a 28-kDa species. D-galactose and N-acetyl-glucosamine decreased the binding of serum IgA to MPO more in HSP than in controls (P <0.05). Conclusions: The conflicting reports on IgA-ANCA may reflect some atypical characteristics of the reaction which can be detected only by some ELISAs. We suggest that not an antigen-antibody reaction but a lectinic interaction due to abnormal composition of IgA carbohydrate side chains may account for the IgA-ANCA reaction in patients with HSP nephritis.     

Urinary leukotriene E(4), eosinophil protein X, and nasal eosinophil cationic protein are not associated with respiratory symptoms in 1-year-old children

BACKGROUND: Eosinophilic airways inflammation forms the pathophysiologic basis for a proportion of children at risk of developing recurrent wheezing. Early preventive measures and/or anti-inflammatory treatment may be guided by the identification of such children. We aimed to study the relationship between respiratory symptoms and indirect markers of airway inflammation. METHODS: We measured eosinophil protein X (EPX) and leukotriene E(4) (LTE(4)) in urine, as well as eosinophil cationic protein (ECP) in nasal lavages, in a random sample of 1-year-old children with a family history of atopy who participated in an international multicenter study on the prevention of allergy in Europe. For urine analyses, 10 children with upper respiratory illness and 19 healthy children without a family history of atopy were also enrolled. Endogenous urinary LTE(4) was separated by HPLC and determined by enzyme immunoassay with a specific antibody. The concentrations of nasal ECP and urinary EPX were determined by RIA analysis. RESULTS: One hundred and ten children (mean age: 1.05+/-0.1 years) were enrolled. Prolonged coughing during the first year of life was reported in 29 children, wheezy breathing in 17 children, and dry skin in 33 children. A doctor's diagnosis of wheezy bronchitis was given to 17 children. Sensitization to dust mites (specific IgE > or =1.43 ML/units) was detected in two children. Children with a doctor's diagnosis of atopic dermatitis within the first 12 months of life (n=6) had significantly higher urinary EPX than children without this (66.7 vs 30.1 microg/mmol creatinine, P=0.01). Urinary excretion of EPX and LTE4 showed a weak correlation (r=0.22, P=0.02). There were no significant differences in urinary excretion of EPX and LTE(4) or nasal ECP between children with and without respiratory symptoms (P>0.1). CONCLUSIONS: At the age of 1 year, urinary EPX is increased in children with atopic dermatitis. With regard to respiratory symptoms, urinary and nasal inflammatory parameters are not helpful in characterizing the phenotype of a single patient.     

Epidemiological study of pathogenic fungi in China: 1986 and 1996

目的　研究 1986年 - 1996年 ,我国致病真菌菌群的变化情况。方法　 1986年 1月 1日 - 12月 31日和 1996年 1月 1日 - 12月 31日在全国 2 5个省、市、自治区 4 0多个有代表性的单位对临床或现场确定的致病菌进行了动态研究 ,就病原菌变迁、各区动态情况和具体疾病等作了详细分析。结果　发现 10年间较易治疗的皮肤癣菌比例下降 ,而较难治疗的酵母菌和霉菌比例升高。结论　 10年间致病真菌菌群的变化较大 ,我们应根据变化情况进行相应的研究及制定出相应治疗措施     

Multicentre international liver tumour study protocol of the case-control study on hepatocellular cancer

Toxicological evidence has recently shown that cyproterone acetate (CPA) is associated with increased adduct formation in liver cell cultures that was interpreted as a possible sign for genotoxicity. Likewise, a few spontaneous reports of liver cancer associated to CPA were published. This led to an alert announced by the German Drug Regulators. One reason to design a case-control study on hepatocellular cancer (HCC) and oral contraceptives (OC's) use (and specific subtypes such as CPA-containing ones) was that other clinical or pharmacoepidemiological studies were not available which dealt with this suspicion. This idea got support from the fact that most of the earlier case-control studies on HCC and OC were small, did not sufficiently control for confounding by: hepatitis B and C, exposure at work, use of other potentially hepatotoxic drugs and also did not distinguish between different types of OC's. Objectives, hypotheses, methods used and subjects studied are described in this paper. The study began in six countries (Germany, United Kingdom, France, Italy, Spain, Greece) on 1 July 1994. It will be finished by the end of June 1996, and first results can be expected by the end of 1996 or early 1997.     

Immune-based therapies: A review of clinical endpoints used in trials of selected immunologic agents,by the Forum for Collaborative HIV Research

Abstract

While the use of highly active antiretroviral therapy (HAART) has lowered the level of virus in the bloodstream, immune reconstitution may offer additional benefits in maintaining viral suppression and enhancing immune function. New approaches in immune-based therapy (IBT) must be designed to capture endpoints that will allow approval of these agents by regulatory agencies.The challenge is to identify, develop, and validate biomarkers that can serve as endpoints in evaluating the efficacy of immunologic agents in HIV disease.

On December 7-8, 2000, the Forum for Collaborative HIV Research sponsored a workshop, “Immune-Based Therapies and HIV Disease.” Some of the questions discussed at that meeting included: ? What are the appropriate indices to measure immune competence?

? What are the appropriate research designs and endpoints for trials evaluating IBTs?

? What can we learn from the research on IBTs in diseases other than HIV?

? What are the requirements of regulatory agencies for the approval of IBTs?

This report, prepared as background information for participants attending the December workshop, addresses issues related to these discussion questions. The report provides a review of study designs and endpoints used in clinical trials of selected immunologic agents. Eight ofthese agents have been approved by the U.S. Food and Drug Administration (FDA) for use in disease conditions other than HIV and five agents are under study for use in HIV-infected individuals but are not FDA-approved for use in HIV disease.

This report was written by Karen Eddleman, who has derstanding of the medical management of HIV disease and develops recommendations to fill those gaps. The Forum is a public/private partnership, which receives financial support from its governmental and industry members and with in-kind support from its membership within the academic research, patient care, and advocacy communities. For more information about the Forum or to download this report or prior ones, visit the Website at www.hivforum.org. Reprinted with permission from Forum for Collaborative HIV Research (www.hivforum.org).done a remarkable job in identifying and reviewing many difficult references and producing a very reader-friendly report. Alan Landay has provided valuable input andassistance in the creation of this report. Houtan Movafagh provided much needed assistance in finding and copying the many references for this report.

June Bray, PhD – Deputy Director