| 1. |
- Sharma, S., et al.
(författare)
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Human Sera Collected between 1979 and 2010 Possess Blocking-Antibody Titers to Pandemic GII.4 Noroviruses Isolated over Three Decades
- 2017
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Ingår i: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 91:14
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Tidskriftsartikel (refereegranskat)abstract
- The emergence of pandemic GII.4 norovirus (NoV) strains has been proposed to occur due to changes in receptor usage and thereby to lead to immune evasion. To address this hypothesis, we measured the ability of human sera collected between 1979 and 2010 to block glycan binding of four pandemic GII. 4 noroviruses isolated in the last 4 decades. In total, 268 sera were investigated for 50% blocking titer (BT50) values of virus-like particles (VLPs) against pig gastric mucin (PGM) using 4 VLPs that represent different GII. 4 norovirus variants identified between 1987 and 2012. Pre- and postpandemic sera (sera collected before and after isolation of the reference NoV strain) efficiently prevented binding of VLP strains MD145 (1987), Grimsby (1995), and Houston (2002), but not the Sydney (2012) strain, to PGM. No statistically significant difference in virus-blocking titers was observed between pre- and postpandemic sera. Moreover, paired sera showed that blocking titers of >= 160 were maintained over a 6-year period against MD145, Grimsby, and Houston VLPs. Significantly higher serum blocking titers (geometric mean titer [GMT], 1,704) were found among IgA-deficient individuals than among healthy blood donors (GMT, 90.9) (P < 0.0001). The observation that prepandemic sera possess robust blocking capacity for viruses identified decades later suggests a common attachment factor, at least until 2002. Our results indicate that serum IgG possesses antibody-blocking capacity and that blocking titers can be maintained for at least 6 years against 3 decades of pandemic GII. 4 NoV. IMPORTANCE Human noroviruses (NoVs) are the major cause of acute gastroenteritis worldwide. Histo-blood group antigens (HBGAs) in saliva and gut recognize NoV and are the proposed ligands that facilitate infection. Polymorphisms in HBGA genes, and in particular a nonsense mutation in FUT2 (G428A), result in resistance to global dominating GII. 4 NoV. The emergence of new pandemic GII. 4 strains occurs at intervals of several years and is proposed to be attributable to epochal evolution, including amino acid changes and immune evasion. However, it remains unclear whether exposure to a previous pandemic strain stimulates immunity to a pandemic strain identified decades later. We found that prepandemic sera possess robust virus-blocking capacity against viruses identified several decades later. We also show that serum lacking IgA antibodies is sufficient to block NoV VLP binding to HBGAs. This is essential, considering that 1 in every 600 Caucasian children is IgA deficient.
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| 2. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
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IgA Deficiency & Mortality : A Population-Based Cohort Study
- 2013
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Ingår i: Journal of Clinical Immunology. - : Springer Science and Business Media LLC. - 0271-9142 .- 1573-2592. ; 33:8, s. 1317-1324
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Tidskriftsartikel (refereegranskat)abstract
- IgA deficiency has been linked to increased morbidity but data on mortality is lacking. In this population-based prospective cohort study we examined mortality in patients with IgA deficiency compared with the general population. Through six university hospitals in Sweden we identified 2,495 individuals with IgA deficiency (IgA deficiencya parts per thousand currency sign0.07 mg/L) diagnosed between 1980 and 2012. Each patient with IgA deficiency was matched on age, sex, place of residence, and year of diagnosis with up to 10 general population controls (n = 24,509). Data on education level and emigration status were obtained from Statistics Sweden. Our main outcome measure was all-cause mortality retrieved from the nationwide Causes of Death Register, which includes > 99 % of all deaths in Sweden. We used Cox regression to estimate mortality hazard ratios conditioned on the matching factors and adjusted for education level. During 25,367 person-years of follow-up (median 8.3), there were 260 deaths in the IgA deficiency group versus 1,599 deaths during 257,219 person-years (median 8.6) in the general population controls (102 versus 62 deaths per 10,000 person-years; incidence rate difference, 40, 95%CI 28-53, P < .001). This corresponded to a conditional mortality hazard ratio of 1.8 (95%CI 1.6-2.1, P < .001). Relative mortality varied by follow-up time (P < .001) from a hazard ratio of 3.6 (95%CI 2.5-5.3; P < .001) during the first year to 1.9 (95%CI 1.5-2.4; P < .001) year 1-4; 1.9 (95%CI 1.4-2.4; P < .001) year 5-9; 1.5 (1.0-2.2; P = .054) year 10-14.9; and 1.1 (0.7-1.6; P = .66) year 15-25. Effect modification was also seen by age in each stratum of follow-up time, with higher relative mortality in younger than older patients (P < .001). In conclusion, patients with IgA deficiency are at increased risk of death in the first 10 to 15 years after diagnosis.
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