Background Regenerating islet-derived protein 3α (REG3α) is an antimicrobial peptide secreted by intestinal Paneth cells. Circulating REG3α has been identified as a gut damage marker in inflammatory bowel diseases. People living with human immunodeficiency virus (PWH) on antiretroviral therapy (ART) present with an abnormal intestinal landscape leading to microbial translocation, persistent inflammation, and development of non-AIDS comorbidities. Herein, we assessed REG3α as a marker of gut damage in PWH. Methods Plasma from 169 adult PWH, including 30 elite controllers (ECs), and 30 human immunodeficiency virus (HIV)–uninfected controls were assessed. REG3α plasma levels were compared with HIV disease progression, epithelial gut damage, microbial translocation, and immune activation markers. Results Cross-sectionally, REG3α levels were elevated in untreated and ART-treated PWH compared with controls. ECs also had elevated REG3α levels compared to controls. Longitudinally, REG3α levels increased in PWH without ART and decreased in those who initiated ART. REG3α levels were inversely associated with CD4 T-cell count and CD4:CD8 ratio, while positively correlated with HIV viral load in untreated participants, and with fungal product translocation and inflammatory markers in all PWH. Conclusions Plasma REG3α levels were elevated in PWH, including ECs. The gut inflammatory marker REG3α may be used to evaluate therapeutic interventions and predict non-AIDS comorbidity risks in PWH.
The human metapneumovirus (hMPV) was recently identified and linked to acute respiratory tract infections (ARTI). To assess the clinical importance of this virus in infants and children, we developed a rapid and efficient reverse transcription-PCR-based screening method for a large volume of samples and tested retrospectively a collection of 1,132 respiratory specimens submitted over a full year period to the virology laboratory of a large tertiary care pediatric center in Montreal, Canada. A total of 41 samples from 37 patients were positive by this method. During the winter months of 2001, up to 8% of specimens submitted for respiratory virus testing were hMPV positive. Sequencing data of the hMPV M gene revealed that two genogroups of the virus, each of which can be divided into two subgroups, cocirculated during this time period. A case-controlled study was conducted to compare the symptoms associated with hMPV infection with those involving other etiologic agents causing ARTI. Symptoms most frequently observed in hMPV-positive patients were cough, wheezing, and dyspnea, although the symptomatology could differ substantially from patient to patient. No distinct symptom profile could be associated with hMPV. Three nosocomial cases of hMPV infection were identified. Together, our data suggest that hMPV is a significant cause of symptomatic respiratory tract infections in infants and children. The incidence of the disease and the morbidity associated with the infection justify adding hMPV to the list of common respiratory viruses routinely screened for by clinical laboratories.Infection with respiratory viruses is a common cause of morbidity and mortality in childhood. Despite the use of moresensitive diagnostic tools by clinical laboratories, an important proportion of respiratory infections still cannot be associated to any known pathogen.Since the first report of acute respiratory tract infections (ARTI) caused by the human metapneumovirus (hMPV) in 2001 (23), the virus has been detected in a number of countries, suggesting a world-wide distribution (6, 8-10, 13-15, 18-21, 25). hMPV is an enveloped, negative-stranded RNA virus possessing a nonsegmented genome, which has been tentatively classified within the Paramyxoviridae family. The two hMPV genogroups (A and B) that have been characterized to date share an approximate overall identity of 85% at the nucleotide level (20,23,24).In 2002, Peret et al. (20) documented hMPV infection cases in the Canadian province of Quebec and linked the virus to potentially severe illnesses in children. The finding prompted us to investigate the prevalence and the clinical importance of the newly discovered pathogen as a cause of ARTI in the pediatric population. We developed rapid and sensitive reverse transcription-PCR (RT-PCR) assays to detect the virus directly in samples submitted for respiratory virus testing to the virology laboratory of Sainte-Justine Hospital (SJH), a reference pediatric tertiary care center in the city of Montreal, Canada. A total of 41 samples we...
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