Rhinovirus Species–Specific Antibodies Differentially Reflect Clinical Outcomes in Health and Asthma

Megremis, Spyridon; Niespodziana, Katarzyna; Cabauatan, Clarissa R.; Xepapadaki, Paraskevi; Kowalski, Marek L.; Jartti, Tuomas; Bachert, Claus; Finotto, Susetta; West, Peter; Stamataki, Sofia; Lewandowska–Polak, Anna; Lukkarinen, Heikki; Zhang, Nan; Zimmermann, Theodor; Stolz, Frank; Neubauer, A.; Akdiş, Mübeccel; Andreakos, Evangelos; Valenta, Rudolf; Papadopoulos, Nikolaos G.

doi:10.1164/rccm.201803-0575oc

Cited by 36 publications

(35 citation statements)

References 33 publications

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“…Since RSV subgroups A and B differ mainly regarding the sequences of the G protein ( Figure 1 ) whereas there is little variation among their fusion proteins, it may be possible to develop diagnostic tests based on G, which can discriminate subgroup A and B-specific antibody responses. In fact, our finding that the G-specific IgG responses in the subjects investigated in our study were mainly directed against sequential G-derived peptide epitopes indicates that it may be possible to develop serological tests based on subgroup A and B-derived peptides similar to what has been developed for the differential diagnosis of rhinovirus (RV) infections [ 35 , 39 , 40 ]. Our assumption that the G-specific IgG response is directed against non-conformational but rather sequential peptide epitopes is also supported by the finding that denatured and deglycosylated forms of A2-G showed similar and sometimes better IgG reactivity than native A2-G.…”

Section: Discussionmentioning

confidence: 99%

Features of the Human Antibody Response against the Respiratory Syncytial Virus Surface Glycoprotein G

et al. 2020

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Respiratory syncytial virus (RSV) infections are a major cause of serious respiratory disease in infants. RSV occurs as two major subgroups A and B, which mainly differ regarding the surface glycoprotein G. The G protein is important for virus attachment and G-specific antibodies can protect against infection. We expressed the surface-exposed part of A2 strain-derived G (A2-G) in baculovirus-infected insect cells and synthesized overlapping peptides spanning complete A2-G. The investigation of the natural IgG response of adult subjects during a period of one year showed that IgG antibodies (i) recognize G significantly stronger than the fusion protein F0, (ii) target mainly non-conformational, sequential peptide epitopes from the exposed conserved region but also buried peptides, and (iii) exhibit a scattered but constant recognition profile during the observation period. The IgG subclass reactivity profile (IgG1 > IgG2 > IgG4 = IgG3) was indicative of a mixed Th1/Th2 response. Two strongly RSV-neutralizing sera including the 1st WHO standard contained high IgG anti-G levels. G-specific IgG increased strongly in children after wheezing attacks suggesting RSV as trigger factor. Our study shows that RSV G and G-derived peptides are useful for serological diagnosis of RSV-triggered exacerbations of respiratory diseases and underlines the importance of G for development of RSV-neutralizing vaccines.

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Section: Discussionmentioning

confidence: 99%

Features of the Human Antibody Response against the Respiratory Syncytial Virus Surface Glycoprotein G

et al. 2020

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“…Serologic assays for RV infection could help to prove acute infections but such tests are not in routine use. Recently, despite high phylogenetic diversity of RV, the development of RV species-specific antibody test has been successful (49). Integrating studies of host response, microbe detection, and airway microbiome is a modern approach in pneumonia diagnostics (50).…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Hospitalized Rhinovirus-Associated Community-Acquired Pneumonia in Children, Finland, 2003–2014

et al. 2019

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Background: Rhinovirus (RV) is the most common cause of respiratory tract infections in children but, still, the clinical characteristics of RV-associated pneumonia have not been sufficiently investigated.Methods: We identified children and adolescents younger than 18 years of age treated for community-acquired pneumonia as inpatients at the Turku University Hospital from 2003 to 2014 and analyzed for RV by PCR of a respiratory tract specimen. We collected the data from medical records and compared RV-positive children with RV-negative children.Results: Of the study population of 313 children with pneumonia who were studied for RV, it was detected in 82 (26%). RV-positive children were younger (median age 2.6 years, interquartile range [IQR] 1.1–4.6 vs. 3.5 years, IQR 1.7–8.3, p = 0.002) and they had more often a history of preterm birth (16% vs. 5%, adjusted odds ratio 2.89, 95% confidence interval 1.21–6.92, p = 0.017) than RV-negative children. RV-positive children had a higher median white blood cell count than RV-negative children at presentation with pneumonia. The signs, symptoms, and severity of pneumonia were mostly similar in RV-positive and RV-negative children.Conclusions: RV was frequently detected in young children hospitalized with community-acquired pneumonia. We identified premature birth as a factor associated with RV-positive pneumonia. The clinical features of pneumonia did not clearly differ between RV-positive and RV-negative children. Further studies are needed to clarify the clinical significance of detection of RV in children with pneumonia.

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“…Other regularly detected CARVs in SOT and HCT include HRV, HCoV, HAdV, and HBoV, yet information on clinical presentation and impact is limited to selective case series in SOT and retrospective studies in allogeneic HCT recipients. A significant component of the uncertainty regarding these agents derives from the fact that (i) prolonged asymptomatic shedding has been observed (172); (ii) there are numerous serotypes/genotypes of HRVs and other enteroviruses, HCoVs, and HAdVs that are not readily differentiated or quantified by multiplex NAT diagnostics; (iii) the serotype/genotype may confer only limited cross-immunity; and (iv) the respective immune status with respect to antibody titers or cellular immunity has not been consistently assessed (173)(174)(175)(176)(177). Thus, persistent and prolonged shedding versus re-/ superinfection with another subtype is not readily identified.…”

Section: Other Carvs In Sot and Allogeneic Hctmentioning

confidence: 99%

Community-Acquired Respiratory Viruses in Transplant Patients: Diversity, Impact, Unmet Clinical Needs

2019

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SUMMARY Patients undergoing solid-organ transplantation (SOT) or allogeneic hematopoietic cell transplantation (HCT) are at increased risk for infectious complications. Community-acquired respiratory viruses (CARVs) pose a particular challenge due to the frequent exposure pre-, peri-, and posttransplantation. Although influenza A and B viruses have a top priority regarding prevention and treatment, recent molecular diagnostic tests detecting an array of other CARVs in real time have dramatically expanded our knowledge about the epidemiology, diversity, and impact of CARV infections in the general population and in allogeneic HCT and SOT patients. These data have demonstrated that non-influenza CARVs independently contribute to morbidity and mortality of transplant patients. However, effective vaccination and antiviral treatment is only emerging for non-influenza CARVs, placing emphasis on infection control and supportive measures. Here, we review the current knowledge about CARVs in SOT and allogeneic HCT patients to better define the magnitude of this unmet clinical need and to discuss some of the lessons learned from human influenza virus, respiratory syncytial virus, parainfluenzavirus, rhinovirus, coronavirus, adenovirus, and bocavirus regarding diagnosis, prevention, and treatment.

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Rhinovirus Species–Specific Antibodies Differentially Reflect Clinical Outcomes in Health and Asthma

Cited by 36 publications

References 33 publications

Features of the Human Antibody Response against the Respiratory Syncytial Virus Surface Glycoprotein G

Features of the Human Antibody Response against the Respiratory Syncytial Virus Surface Glycoprotein G

Characteristics of Hospitalized Rhinovirus-Associated Community-Acquired Pneumonia in Children, Finland, 2003–2014

Community-Acquired Respiratory Viruses in Transplant Patients: Diversity, Impact, Unmet Clinical Needs

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