Cancer risks in childhood and adolescence among the offspring of immigrants to Sweden

We used the nation-wide Swedish Family-Cancer Database to analyse the risk of nervous system tumours, leukaemia and non-Hodgkin's lymphoma in age groups 0–4 and 0–19 years among Swedish-born offspring of immigrants. The study included 850 000 individuals with an immigrant background, including European, Asian and American parents. We calculated standardised incidence ratios for the above three malignancies using Swedish offspring as a reference. Subjects were grouped by region or by selected countries of parental origin. No group differed significantly from Swedes in the occurrence of nervous system neoplasm or leukaemia. Offspring of Yugoslav fathers (SIR 2.27) and Turkish parents were at increased risk of non-Hodgkin's lymphoma. The highest risk was noted for non-Hodgkin's lymphoma among young offspring (0–4 years) of two Turkish parents (6.87). The currently available limited data on rates for childhood non-Hodgkin's lymphoma in these countries do not explain the risk in the offspring of immigrants. Yugoslavs and Turks are recent immigrant groups to Sweden, and their offspring have been subject to much population mixing, perhaps leading to recurring infections and immunological stimulation, which may contribute to their excess of lymphomas

Amyloid-β oligomer specificity mediated by the IgM isotype : implications for a specific protective mechanism exerted by endogenous auto-antibodies

Background Alzheimers disease (AD) has been strongly linked to an anomalous self-assembly of the amyloid-β peptide (Aβ). The correlation between clinical symptoms of AD and Aβ depositions is, however, weak. Instead small and soluble Aβ oligomers are suggested to exert the major pathological effects. In strong support of this notion, immunological targeting of Aβ oligomers in AD mice-models shows that memory impairments can be restored without affecting the total burden of Aβ deposits. Consequently a specific immunological targeting of Aβ oligomers is of high therapeutic interest. Methodology/Principal Findings Previously the generation of conformational-dependent oligomer specific anti-Aβ antibodies has been described. However, to avoid the difficult task of identifying a molecular architecture only present on oligomers, we have focused on a more general approach based on the hypothesis that all oligomers expose multiple identical epitopes and therefore would have an increased binding to a multivalent receptor. Using the polyvalent IgM immunoglobulin we have developed a monoclonal anti-Aβ antibody (OMAB). OMAB only demonstrates a weak interaction with Aβ monomers and dimers having fast on and off-rate kinetics. However, as an effect of avidity, its interaction with Aβ-oligomers results in a strong complex with an exceptionally slow off-rate. Through this mechanism a selectivity towards Aβ oligomers is acquired and OMAB fully inhibits the cytotoxic effect exerted by Aβ(1-42) at highly substoichiometric ratios. Anti-Aβ auto-antibodies of IgM isotype are frequently present in the sera of humans. Through a screen of endogenous anti-Aβ IgM auto-antibodies from a group of healthy individuals we show that all displays a preference for oligomeric Aβ. Conclusions/Significance Taken together we provide a simple and general mechanism for targeting of oligomers without the requirement of conformational-dependent epitopes. In addition, our results suggest that IgM anti-Aβ auto-antibodies may exert a more specific protective mechanism in vivo than previously anticipated