Combined Rapid (TUBEX) Test for Typhoid-Paratyphoid A Fever Based on Strong Anti-O12 Response: Design and Critical Assessment of Sensitivity

Rapid diagnostics can be accurate but, often, those based on antibody detection for infectious diseases are unwittingly underrated for various reasons. Herein, we described the development of a combined rapid test for two clinically-indistinguishable bacterial diseases, typhoid and paratyphoid A fever, the latter fast emerging as a global threat. By using monoclonal antibodies (mAbs) to bacterial antigens of known chemical structures as probes, we were able to dissect the antibody response in patients at the level of monosaccharides. Thus, a mAb specific for a common lipopolysaccharide antigen (O12) found in both the causative organisms was employed to semi-quantify the amounts of anti-O12 antibodies present in both types of patients in an epitope-inhibition particle-based (TUBEX) immunoassay. This colorimetric assay detected not only anti-O12 antibodies that were abundantly produced, but also, by steric hindrance, antibodies to an adjoining epitope (O9 or O2 in the typhoid or paratyphoid bacillus, respectively). Sensitivity and, particularly, reaction intensities, were significantly better than those obtained using an anti-O9 or anti-O2 mAb-probe in the examination of paired sera from 22 culture-confirmed typhoid patients (sensitivity, 81.8% vs 75.0%) or single sera from 36 culture-confirmed paratyphoid patients (52.8% vs 28.6), respectively. Importantly, sensitivity was better (97.1% for typhoid, 75.0% for paratyphoid) if allowance was made for the absence of relevant antibodies in certain specimens as determined by an independent, objective assay (ELISA) — such specimens might have been storage-denatured (especially the older paratyphoid samples) or procured from non-responders. Benchmarking against ELISA, which revealed high concordance between the two tests, was useful and more appropriate than comparing with culture methods as traditionally done, since antibody tests and culture target slightly different stages of these diseases. Paired sera analysis was insightful, revealing 64% of typhoid patients who had no change in antibody titer over 4–16 days, and 14% with no IgM-IgG class-switching

Positive Association between Aspirin-Intolerant Asthma and Genetic Polymorphisms of FSIP1: a Case-Case Study

<p>Abstract</p> <p>Background</p> <p>Aspirin-intolerant asthma (AIA), which is caused by non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, causes lung inflammation and reversal bronchi reduction, leading to difficulty in breathing. Aspirin is known to affect various parts inside human body, ranging from lung to spermatogenesis. <it>FSIP1</it>, also known as <it>HDS10</it>, is a recently discovered gene that encodes fibrous sheath interacting protein 1, and is regulated by amyloid beta precursor protein (APP). Recently, it has been reported that a peptide derived from APP is cleaved by α disintegrin and metalloproteinase 33 (<it>ADAM33</it>), which is an asthma susceptibility gene. It has also been known that the <it>FSIP1 </it>gene is expressed in airway epithelium.</p> <p>Objectives</p> <p>Aim of this study is to find out whether <it>FSIP1 </it>polymorphisms affect the onset of AIA in Korean population, since it is known that AIA is genetically affected by various genes.</p> <p>Methods</p> <p>We conducted association study between 66 single nucleotide polymorphisms (SNPs) of the <it>FSIP1 </it>gene and AIA in total of 592 Korean subjects including 163 AIA and 429 aspirin-tolerant asthma (ATA) patients. Associations between polymorphisms of <it>FSIP1 </it>and AIA were analyzed with sex, smoking status, atopy, and body mass index (BMI) as covariates.</p> <p>Results</p> <p>Initially, 18 SNPs and 4 haplotypes showed associations with AIA. However, after correcting the data for multiple testing, only one SNP showed an association with AIA (corrected <it>P</it>-value = 0.03, OR = 1.63, 95% CI = 1.23-2.16), showing increased susceptibility to AIA compared with that of ATA cases. Our findings suggest that <it>FSIP1 </it>gene might be a susceptibility gene for aspirin intolerance in asthmatics.</p> <p>Conclusion</p> <p>Although our findings did not suggest that SNPs of <it>FSIP1 </it>had an effect on the reversibility of lung function abnormalities in AIA patients, they did show significant evidence of association between the variants in <it>FSIP1 </it>and AIA occurrence among asthmatics in a Korean population.</p