Autoantibodies against cytokines: back to human genetics

Blood (Impact Factor: 9.78). 02/2013; 121(8):1246-7. DOI: 10.1182/blood-2013-01-474213
Source: PubMed
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    ABSTRACT: Although previously considered as the safest of the live virus vaccines, reports published since 2001 indicate that live yellow fever virus vaccine can cause a severe, often fatal, multisystemic illness, yellow fever vaccine-associated viscerotropic disease (YEL-AVD), that resembles the disease it was designed to prevent. This review was prompted by the availability of a listing of the cumulative cases of YEL-AVD, insights from a statistical method for analyzing risk factors and re-evaluation of previously published data. The purpose of this review is to identify and analyze risk groups based on gender, age, outcome and predisposing illnesses. Using a passive surveillance system in the US, the incidence was reported as 0.3-0.4 cases per 100,000. However, other estimates range from 0 to 12 per 100,000. Identified and potential risk groups for YEL-AVD include elderly males, women between the ages of 19 and 34, people with a variety of autoimmune diseases, individuals who have been thymectomized because of thymoma, and infants and children ≤11 years old. All but the last group are supported by statistical analysis. The confirmed risk groups account for 77% (49/64) of known cases and 76% (32/42) of the deaths. The overall case fatality rate is 66% (42/64) with a rate of 80% (12/15) in young women, in contrast to 50% (13/26) in men ≥56 years old. Recognition of YEL-AVD raises the possibility that similar reactions to live chimeric flavivirus vaccines that contain a yellow fever virus vaccine backbone could occur in susceptible individuals. Delineation of risk groups focuses the search for genetic mutations resulting in immune defects associated with a given risk group. Lastly, identification of risk groups encourages concentration on measures to decrease both the incidence and the severity of YEL-AVD.
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    ABSTRACT: Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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    ABSTRACT: Cytokines regulate many aspects of cell growth and differentiation and play pivotal roles in the orchestration of immune defence against invading pathogens. Though 'self' proteins, they are potentially immunogenic and can give rise to anti-cytokine autoantibodies (aCA). The main foci of the article are a critical summary of the various methodologies applied for detecting and measuring aCA and a broad review of studies of the occurrence, characterization and clinical relevance of aCA in normal healthy individuals, patients with autoimmune diseases or microbial infections and aCA in patients whose disease is treated with recombinant cytokine products. The need for technical and methodological improvement of assays, including validation and standardization, together with approaches to harmonize calculation and reporting of results is also discussed.
    Expert Review of Clinical Immunology 06/2014; DOI:10.1586/1744666X.2014.918848 · 3.34 Impact Factor