Immunoglobulin A responses to Puumala hantavirus

Abstract

Puumala hantavirus (PUUV) causes nephropathia epidemica (NE), a form of haemorrhagic fever with renal syndrome that occurs in northern and central Europe. The immunoglobulin A (IgA) response in NE patients was studied. The levels of total serum IgA in acute-phase samples from NE patients were found to be significantly elevated when compared with the levels in healthy controls. ELISAs for detection of the IgA1 and IgA2 responses against each PUUV structural protein (N, G1 and G2) were developed and evaluated. Sequential sera from NE patients (acute, convalescent, 2-year) and 10-20 year NE-convalescent sera were examined. Most patients developed detectable levels of IgA1 against N and G2, while the G1 responses were low or undetectable. Seven of nine 10-20 year sera contained virus-specific IgA1, which may indicate the prolonged presence of viral antigens after the initial infection. PEPSCAN analysis revealed several IgA-reactive antigenic regions in the N protein. Serum IgA and IgG was purified by affinity chromatography and examined by a virus-neutralization assay. Three of five sera from acute-phase NE patients contained neutralizing IgA1. The diagnostic potential of the PUUV-specific IgA1 response was evaluated. The N and G2 assays showed specificities of 100% with sensitivities of 91 and 84%, respectively, compared with an IgM mu-capture ELISA. Several NE patients, clinically diagnosed for acute PUUV infection, with borderline or undetectable levels of PUUV-specific IgM, were found to be highly positive for the presence of PUUV N-specific serum IgA1, proving the diagnostic value of IgA analysis as a complement to detection of IgM.

Development of Novel Immunoglobulin G (IgG), IgA, and IgM Enzyme Immunoassays Based on Recombinant Puumala and Dobrava Hantavirus Nucleocapsid Proteins

“…For one patient without detectable IgM, the evidence of acute infection was confirmed by IgA detection accompanied by increasing IgG titers in follow-up. In previous studies, another MAb capture IgA ELISA (specificity 100%) was found to detect 91% of IgM anti-N-positive sera used (8). In agreement with previous observations (8,12,15,34), the N-specific IgA response has been found to be decreased in convalescent-and late-convalescent-phase sera.…”

“…In previous studies, another MAb capture IgA ELISA (specificity 100%) was found to detect 91% of IgM anti-N-positive sera used (8). In agreement with previous observations (8,12,15,34), the N-specific IgA response has been found to be decreased in convalescent-and late-convalescent-phase sera. However, particularly for certain DOBV-infected patients, a persistence of IgM and/or IgA antibodies was observed in four persons (three of them IgM positive and three of them IgA positive) even until the end of the observation period of 2 to 3 years.…”

Hantaviruses: Molecular Biology, Evolution and Pathogenesis

“…Thus, IgA antibodies, like IgM antibodies, are markers of an early stage in infection [143]. Similar observations have been made for other viruses which primarily infect mucosal surfaces including measles-, rota-, and enteroviruses [144,[144][145][146].…”

Immune responses to Puumala virus infection and the pathogenesis of nephropathia epidemica

“…An alternative way that has been used to diagnose acute/recent PUUV infection is to demonstrate low-avidity IgG antibodies (eluted by 8 M urea), either in an immunofluorescence test or enzyme immunoassay [22,23]. Acute-phase PUUV and ANDV patients also develop IgA 1 antibodies at least to the N protein [20,24], but this has not been applied to routine diagnostics. In addition, PUUV infection induces low levels of specific IgE antibodies but without correlation to clinical parameters [25].…”

“…after the first week after onset of NE [38][39][40]. Possible viral persistence has been suggested, since high levels of PUUV-specific IgG 4 and of IgA 1 antibodies [24,41], which characterize many chronic human viral infections, such as hepatitis B and herpes group virus infections, are seen in late convalescent serum samples.…”