Interferon antibodies in patients with infectious diseases

Interferons (IFNs) are generally recognized as the most important therapeutic agent in some infectious diseases such as chronic hepatitis B and C. Since the early clinical trials it was documented that the therapeutic use of IFNs could be complicated by the development of antibodies able to neutralize or to bind to the IFN molecule. After several years of research it is now widely accepted that the presence of circulating anti-IFN antibodies may affect the response to IFN. Here we summarize what is currently know on the clinical significance of antibodies to IFN in IFN-treated viral diseases patients.     

Types of immune response in acute infectious diseases

The author's concept on the system of self regulation of immune response is described. Four types of this response are proposed, which differ by total intensity of cytokine reaction, the development time as well as manifestation degree of non specific immunosuppression, and, most importantly, the profile of specific immune response to the antigens of the infective agent. These four types of immune response are closely linked with increased severity of clinical manifestations.     

Serodiagnosis of infectious diseases with antigen microarrays

AIMS: To generate protein microarrays by printing microbial antigens on slides to enable the simultaneous determination in human sera of antibodies directed against Toxoplasma gondii, rubella virus, cytomegalovirus and herpes simplex virus (HSV) types 1 and 2. METHODS AND RESULTS: Antigens were printed on activated glass slides using high-speed robotics. The slides were incubated with serum samples and subsequently with fluorescently labelled secondary antibodies. Human IgG and IgM bound to the printed antigens were detected using confocal scanning microscopy and quantified with internal calibration curves. The microarray assay could detect as little as 0.5 pg of both IgG and IgM bound onto the glass surface. Precision profiles ranged from 1.7 to 18.5% for all the antigens. Microarrays and commercial ELISAs were utilized to detect serum antibodies against the ToRCH antigens in a panel of characterized human sera. Overall >80% concordance was obtained between microarray and ELISA kits in the classification of sera. CONCLUSIONS: These results indicate that the microarray is a suitable assay format for the serodiagnosis of infectious diseases. SIGNIFICANCE AND IMPACT OF STUDY: Antigen microarrays can be optimized for clinical use, their performance is equivalent to ELISA but they offer significant advantages in throughput, convenience and cost.     

Follow up of patients presenting with fatigue to an infectious diseases clinic.

OBJECTIVES--To determine the symptomatic and functional status during follow up of patients referred to hospital with unexplained fatigue and to identify patient variables associated with persistent functional impairment. DESIGN--Follow up by postal questionnaire six weeks to four years (median 1 year) after initial clinical assessment of patients referred to hospital during 1984-8. SETTING--Infectious diseases outpatient clinic in a teaching hospital. PATIENTS--200 consecutive patients with fatigue of uncertain cause for at least six weeks; 177 fulfilled the inclusion criteria. MAIN OUTCOME MEASURES--Findings at initial assessment; current symptoms, beliefs about the cause of illness, coping behaviours emotional disorder, social variables including membership of self help organizations, and degrees of recovery and functional impairment from questionnaire responses. RESULTS--144 (81%) patients returned completed questionnaires. Initial assessment did not indicate the cause of fatigue, other than preceding infection. The proportion of patients with functional impairment was significantly smaller with longer follow up (33% (11/33) at two to four years, 73% (29/40) at six weeks to six months; chi 2 for trend = 12.5, df = 1; p less than 0.05). Functional impairment was significantly associated with belief in a viral cause of the illness (odds ratio = 3.9; 95% confidence interval 1.5 to 9.9), limiting exercise (3.2; 1.5 to 6.6), avoiding alcohol (4.5; 1.8 to 11.3), changing or leaving employment (3.1; 1.4 to 6.9), belonging to a self help organization (7.8; 2.5 to 23.9), and current emotional disorder (4.4; 2.0 to 9.3). CONCLUSIONS--Short term prognosis for recovery of function was poor but improved with time. Most patients had made a functional recovery by two years after initial clinic attendance. Impaired functioning was more likely with certain patient characteristics. Prospective studies are required to clarify whether these associations are the consequences of a more disabling illness or indicate factors contributing to impaired function.     

Structural proteomics of the SARS coronavirus: a model response to emerging infectious diseases

A number of structural genomics/proteomics initiatives are focused on bacterial or viral pathogens. In this article, we will review the progress of structural proteomics initiatives targeting the SARS coronavirus (SARS-CoV), the etiological agent of the 2003 worldwide epidemic that culminated in approximately 8,000 cases and 800 deaths. The SARS-CoV genome encodes 28 proteins in three distinct classes, many of them with unknown function and sharing low similarity to other proteins. The structures of 16 SARS-CoV proteins or functional domains have been determined to date. Remarkably, eight of these 16 proteins or functional domains have novel folds, indicating the uniqueness of the coronavirus proteins. The results of SARS-CoV structural proteomics initiatives will have several profound biological impacts, including elucidation of the structure-function relationships of coronavirus proteins; identification of targets for the design of anti-viral compounds against SARS-CoV and other coronaviruses; and addition of new protein folds to the fold space, with further understanding of the structure-function relationships for several new protein families. We discuss the use of structural proteomics in response to emerging infectious diseases such as SARS-CoV and to increase preparedness against future emerging coronaviruses.     

Emerging infectious diseases associated with bat viruses

Bats play important roles as pollen disseminators and pest predators. However, recent interest has focused on their role as natural reservoirs of pathogens associated with emerging infectious diseases. Prior to the outbreak of severe acute respiratory syndrome (SARS), about 60 bat virus species had been reported. The number of identified bat viruses has dramatically increased since the initial SARS outbreak, and most are putative novel virus species or genotypes. Serious infectious diseases caused by previously identified bat viruses continue to emerge throughout in Asia, Australia, Africa and America. Intriguingly, bats infected by these different viruses seldom display clinical symptoms of illness. The pathogenesis and potential threat of bat-borne viruses to public health remains largely unknown. This review provides a brief overview of bat viruses associated with emerging human infectious diseases.     

Transcriptomic analysis of the sulfate starvation response of Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic pathogen that causes a number of infections in humans, but is best known for its association with cystic fibrosis. It is able to use a wide range of sulfur compounds as sources of sulfur for growth. Gene expression in response to changes in sulfur supply was studied in P. aeruginosa E601, a cystic fibrosis isolate that displays mucin sulfatase activity, and in P. aeruginosa PAO1. A large family of genes was found to be upregulated by sulfate limitation in both isolates, encoding sulfatases and sulfonatases, transport systems, oxidative stress proteins, and a sulfate-regulated TonB/ExbBD complex. These genes were localized in five distinct islands on the genome and encoded proteins with a significantly reduced content of cysteine and methionine. Growth of P. aeruginosa E601 with mucin as the sulfur source led not only to a sulfate starvation response but also to induction of genes involved with type III secretion systems.