Lack of association between polymorphisms of MASP2 and susceptibility to SARS coronavirus infection

<p>Abstract</p> <p>Background</p> <p>The pathogenesis of severe acute respiratory disease syndrome (SARS) is not fully understood. One case-control study has reported an association between susceptibility to SARS and <it>mannan-binding lectin </it>(<it>MBL</it>) in China. As the downstream protein of <it>MBL</it>, variants of the <it>MBL</it>-associated serine protease-2 (<it>MASP2</it>) gene may be associated with SARS coronavirus (SARS-CoV) infection in the same population.</p> <p>Methods</p> <p>Thirty individuals with SARS were chosen for analysis of <it>MASP2 </it>polymorphisms by means of PCR direct sequencing. Tag single nucleotide polymorphisms (tagSNPs) were chosen using pairwise tagging algorithms. The frequencies of four tag SNPs (rs12711521, rs2261695, rs2273346 and rs7548659) were ascertained in 376 SARS patients and 523 control subjects, using the Beckman SNPstream Ultra High Throughput genotyping platform.</p> <p>Results</p> <p>There is no significant association between alleles or genotypes of the <it>MASP2 </it>tagSNP and susceptibility to SARS-CoV in both Beijing and Guangzhou populations. Diplotype (rs2273346 and rs12711521)were analyzed for association with susceptibility to SARS, no statistically significant evidence of association was observed. The Beijing and Guangzhou sample groups were homogeneous regarding demographic and genetic parameters, a joined analysis also showed no statistically significant evidence of association.</p> <p>Conclusion</p> <p>Our data do not suggest a role for <it>MASP2 </it>polymorphisms in SARS susceptibility in northern and southern China.</p

Human TGFalpha-derived peptide TGFalphaL3 fused with superantigen for immunotherapy of EGFR-expressing tumours

Abstract Background Monoclonal antibodies have been employed as targeting molecules of superantigen for the preclinical treatment of a variety of tumours. However, other targeting molecules, such as tumour-related ligands or peptides, are less exploited. Here, we tested other targeting molecules by genetically fusing the third loop of transforming growth factor alpha (TGFalphaL3) to mutant staphylococcal enterotoxin A (SEAD227A). Results The resultant fusion proteins were expressed in E. coli and purified to homogeneity through a Ni-NTA affinity column. Fusion protein TGFalphaL3SEAD227A can promote splenocyte proliferation to a level comparable to recombinant SEA (rSEA) and bind to EGFR-expressing tumour cells in an EGFR-dependent way. Consistent with these observations, TGFalphaL3SEAD227A exerted an inhibitory effect on the growth of EGFR-expressing tumour cells both in vitro and in vivo. Notably, significant infiltrations of CD8+ and CD4+ T cells were detected in the tumour tissues of these C57BL/6 mice treated with TGFalphaL3SEAD227A, suggesting the involvement of T cells in this tumour-inhibitory process. Conclusions The data here showed that TGFαL3 is capable of targeting superantigen to tumours and exerting an inhibitory effect on tumour growth, which enables TGFαL3SEAD227A to be an attractive candidate for the immunotherapy of EGFR-expressing tumours.</p