New Sandwich‐Type Enzyme‐Linked Immunosorbent Assay for Human MxA Protein in a Whole Blood Using Monoclonal Antibodies Against GTP‐Binding Domain for Recognition of Viral Infection

Kawamura, Mizuho; Kusano, Akira; Furuya, Akiko; Hanai, Nobuo; Tanigaki, Hideki; Tomita, Akihito; Horiguchi, Akira; Nagata, Kyosuke; Itazawa, Toshiko; Adachi, Yuichi; Okabe, Yasunori; Miyawaki, Toshio; Kohno, Hiroaki

doi:10.1002/jcla.21507

Cited by 10 publications

(13 citation statements)

References 29 publications

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“…Moreover, a deficiency in the receptor for IFN is reported to increase the severity of respiratory viral infection ( 63 ). MxA has been found to be elevated in common respiratory viral infections as well as common viral gastrointestinal infections ( Table 2 ) ( 17 , 25 – 27 , 64 , 65 ).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a combined MxA and CRP point-of-care immunoassay to identify viral and/or bacterial immune response in patients with acute febrile respiratory infection

Sambursky¹,

Shapiro

2015

European Clinical Respiratory Journal

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BackgroundChallenges in the clinical differentiation of viral and/or bacterial respiratory infection lead to the misappropriation of antibiotics and increased healthcare costs. A tool to facilitate rapid and accurate point-of-care (POC) differentiation is needed.Methods and findingsA prospective, single center, blinded, observational clinical trial was conducted at Beth Israel Deaconess Medical Center from December 2012 to August 2013 to determine the accuracy of a POC immunoassay to identify a clinically significant immune response to viral and/or bacterial infection. Sixty patients with acute febrile respiratory infection (19 pharyngitis and 41 lower respiratory tract infection [LRTI]) were enrolled. Participants provided fingerstick blood for immunoassay testing (myxovirus A [MxA] and c-reactive protein [CRP]) and four oropharyngeal samples for viral PCR and routine bacterial cell culture. A venous blood sample was collected. An ELISA was used to measure CRP and MxA. Paired serological testing was used to confirm atypical bacteria. A urine sample was provided for Streptococcus and Legionella antigen testing. Patients with suspected LRTI had sputum and blood cultures, chest X-ray, and WBC count measured. Viral infection was confirmed if oropharyngeal PCR was positive for viral pathogens. Bacterial infection was confirmed in positive throat or sputum cultures. Elevated immunoglobulin M antibodies or twofold increase in IgG antibodies between acute and convalescent phase indicated atypical bacteria. Positive Streptococcus or Legionella urine antigen assays also confirmed bacterial infection. The immunoassay correctly categorized subjects as 92% (22/24) negative, 80% (16/20) with bacterial infection, and 70% (7/10) with viral infection.ConclusionsThe interplay between an MxA value and a semi-quantitative CRP value can aid in the differentiation of infectious etiology. In isolation, neither MxA nor CRP alone is sensitive or specific. However, the pattern of results in a rapid immunoassay provides a sensitive and specific method to differentiate acute febrile respiratory infections. This diagnostic information may help reduce antibiotic misuse and resistance and lower healthcare costs.

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Section: Discussionmentioning

confidence: 99%

Evaluation of a combined MxA and CRP point-of-care immunoassay to identify viral and/or bacterial immune response in patients with acute febrile respiratory infection

Sambursky¹,

Shapiro

2015

European Clinical Respiratory Journal

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“…5,6,9,19 The thresholds chosen differed from 1 study to another, ranging from 36.7 ng/mL to 500 ng/mL, 6,19,20 related to methodologic MxA detection differences, ROC curve analyses, or desired Se or Sp. In our study, MxA levels above the 200-ng/mL threshold predicted a viral infection with useful LRs for practice.…”

Section: Validation Of Mxa As a Marker Of Viral Infectionmentioning

confidence: 99%

“…27 The use of this marker of viral infection is therefore also promising in specific patient populations at high risk of infectious complications. The recent development of a sandwichtype enzyme-linked immunosorbent assay for human MxA protein in blood in a 96-well plate format 19 could facilitate the automation of MxA measurement and its introduction in the routine diagnostic laboratory.…”

Section: Validation Of Mxa As a Marker Of Viral Infectionmentioning

confidence: 99%

Diagnosis of Viral Infections Using Myxovirus Resistance Protein A (MxA)

et al. 2015

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“…Many studies have shown that MxA protein expression in peripheral blood is a sensitive and specific marker of viral infection [24][25][26][27][28][29][30][31]. Higher MxA levels are found in viral infections compared with bacterial infections because MxA protein is induced exclusively by type I IFN and not by IFN-gamma, IL-1, TNF-alpha or any of the other cytokines expressed during bacterial infection [32].…”

Section: Host Immune Response Assaymentioning

confidence: 99%

Multi-tiered screening and diagnosis strategy for COVID-19: a model for sustainable testing capacity in response to pandemic

et al. 2020

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Coronavirus disease 2019 , caused by novel enveloped single stranded RNA coronavirus (SARS-CoV-2), is responsible for an ongoing global pandemic. While other countries deployed widespread testing as an early mitigation strategy, the U.S. experienced delays in development and deployment of organism identification assays. As such, there is uncertainty surrounding disease burden and community spread, severely hampering containment efforts. COVID-19 illuminates the need for a tiered diagnostic approach to rapidly identify clinically significant infections and reduce disease spread. Without the ability to efficiently screen patients, hospitals are overwhelmed, potentially delaying treatment for other emergencies. A multi-tiered, diagnostic strategy incorporating a rapid host immune response assay as a screening test, molecular confirmatory testing and rapid IgM/IgG testing to assess benefit from quarantine/further testing and provide information on population exposure/herd immunity would efficiently evaluate potential COVID-19 patients. Triaging patients within minutes with a fingerstick rather than hours/days after an invasive swab is critical to pandemic response as reliance on the existing strategy is limited by assay accuracy, time to results, and testing capacity. Early screening and triage is achievable from the outset of a pandemic with point-of-care host immune response testing which will improve response time to clinical and public health actions. KEY MESSAGESDelayed testing deployment has led to uncertainty surrounding overall disease burden and community spread, severely hampering public health containment and healthcare system preparation efforts. A multi-tiered testing strategy incorporating rapid, host immune point-of-care tests can be used now and for future pandemic planning by effectively identifying patients at risk of disease thereby facilitating quarantine earlier in the progression of the outbreak during the weeks and months it can take for pathogen specific confirmatory tests to be developed, validated and manufactured in sufficient quantities. The ability to triage patients at the point of care and support the guidance of medical and therapeutic decisions, for viral isolation or confirmatory testing or for appropriate treatment of COVID-19 and/or bacterial infections, is a critical component to our national pandemic response and there is an urgent need to implement the proposed strategy to combat the current outbreak. ARTICLE HISTORY

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New Sandwich‐Type Enzyme‐Linked Immunosorbent Assay for Human MxA Protein in a Whole Blood Using Monoclonal Antibodies Against GTP‐Binding Domain for Recognition of Viral Infection

Abstract: We have developed a new ELISA for measuring MxA protein in human whole blood using mAbs specific for the GTP-binding domain of MxA. This ELISA has analytical performance enough for routine clinical assay and can be used in detecting the possibility of viral infection.

Cited by 10 publications

References 29 publications

Evaluation of a combined MxA and CRP point-of-care immunoassay to identify viral and/or bacterial immune response in patients with acute febrile respiratory infection

Evaluation of a combined MxA and CRP point-of-care immunoassay to identify viral and/or bacterial immune response in patients with acute febrile respiratory infection

Diagnosis of Viral Infections Using Myxovirus Resistance Protein A (MxA)

Multi-tiered screening and diagnosis strategy for COVID-19: a model for sustainable testing capacity in response to pandemic

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