The association of RANTES polymorphism with severe acute respiratory syndrome in Hong Kong and Beijing Chinese

<p>Abstract</p> <p>Background</p> <p>Chemokines play important roles in inflammation and antiviral action. We examined whether polymorphisms of <it>RANTES, IP-10 </it>and <it>Mig </it>affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS).</p> <p>Methods</p> <p>We tested the polymorphisms of <it>RANTES, IP-10 </it>and <it>Mig </it>for their associations with SARS in 495 Hong Kong Chinese SARS patients and 578 controls. Then we tried to confirm the results in 356 Beijing Chinese SARS patients and 367 controls.</p> <p>Results</p> <p><it>RANTES </it>-28 G allele was associated with SARS susceptibility in Hong Kong Chinese (<it>P </it>< 0.0001, OR = 2.80, 95%CI:2.11–3.71). Individuals with <it>RANTES </it>-28 CG and GG genotypes had a 3.28-fold (95%CI:2.32–4.64) and 3.06-fold (95%CI:1.47–6.39) increased risk of developing SARS respectively (<it>P </it>< 0.0001). This -28 G allele conferred risk of death in a gene-dosage dependent manner (<it>P </it>= 0.014) with CG and GG individuals having a 2.12-fold (95% CI: 1.11–4.06) and 4.01-fold (95% CI: 1.30–12.4) increased risk. For the replication of <it>RANTES </it>data in Beijing Chinese, the -28 G allele was not associated with susceptibility to SARS. However, -28 CG (OR = 4.27, 95%CI:1.64–11.1) and GG (OR = 3.34, 95%CI:0.37–30.7) were associated with admission to intensive care units or death due to SARS (<it>P </it>= 0.011).</p> <p>Conclusion</p> <p><it>RANTES </it>-28 G allele plays a role in the pathogenesis of SARS.</p

The interferon gamma gene polymorphism +874 A/T is associated with severe acute respiratory syndrome

BACKGROUND: Cytokines play important roles in antiviral action. We examined whether polymorphisms of IFN-γ,TNF-α and IL-10 affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS). METHODS: A case-control study was carried out in 476 Chinese SARS patients and 449 healthy controls. We tested the polymorphisms of IFN-γ,TNF-α and IL-10 for their associations with SARS. RESULTS: IFN-γ +874A allele was associated with susceptibility to SARS in a dose-dependent manner (P < 0.001). Individuals with IFN-γ +874 AA and AT genotype had a 5.19-fold (95% Confidence Interval [CI], 2.78-9.68) and 2.57-fold (95% CI, 1.35-4.88) increased risk of developing SARS respectively. The polymorphisms of IL-10 and TNF-α were not associated with SARS susceptibility. CONCLUSION: IFN-γ +874A allele was shown to be a risk factor in SARS susceptibility

Association of interleukin 10 promoter polymorphisms with systemic lupus erythematosus

abstractpublished_or_final_versiontocPaediatrics and Adolescent MedicineMasterMaster of Philosoph

Tolerogenic and inflammatory properties of natural killer cells after interacting with apoptotic cells and immunoglobulin G opsonizedapoptotic cells

published_or_final_versionPaediatrics and Adolescent MedicineDoctoralDoctor of Philosoph

Essential Role of NK Cells in IgG Therapy for Experimental Autoimmune Encephalomyelitis

<div><p>Intravenous immunoglobulin has long been used in treating autoimmune diseases, although mechanisms remain uncertain. Activating Fcγ receptors are receptors of IgG and reported to be essential in intravenous immunoglobulin (IVIG) therapy. Therefore, we hypothesized natural killer (NK) cells, which express abundant activating Fcγ receptors, are the potential cellular target. In experimental autoimmune encephalomyelitis (EAE), we demonstrated that IgG suppressed disease development in intact, but not in NK cell depleted mice. Adoptive transfer of IgG-treated NK cell could protect mice against EAE, and suppressed interferon γ and interleukin 17 production. The percentage of CD4⁺Foxp3⁺ regulatory T cells was significantly increased. The increase of regulatory T cells was also observed in IgG-treated EAE mice but not in NK cell depleted mice. In vitro experiments confirmed that IgG-treated NK cells enhanced regulatory T cell induction from naïve CD4⁺ T cells. Interestingly, cells from draining lymph nodes produced more interleukin 2 after the adoptive transfer of IgG-treated NK cells. We neutralized interleukin 2 and the induction of CD4⁺Foxp3⁺ T cells by IgG-treated NK cells was significantly reduced. To our knowledge, we identified for the first time the critical role of NK cells in the mechanism of IgG-induced induction of Treg cells in treatment of autoimmunity.</p> </div

IgG-NK cells suppress EAE by inducing CD4⁺Foxp3⁺ Treg cells with stronger inhibitory effect.

<p>EAE was induced in C57BL/6N mice and 1×10⁶ of IgG-NK cells or untreated-NK cells were injected intravenously at the day of EAE induction. (<b>A, B</b>) Cells were isolated from draining LNs 10 days after EAE induction and analyzed by Flow cytometry. Treg cells were identified by intracellular expression of Foxp3 on the gated CD4⁺ cells. Data are displayed as the mean percentage ± SEM of the combined data with 4–6 mice per group from 2 independent experiments. (<b>C, D</b>) 2×10⁴ CFSE-labeled CD4⁺CD25⁻ T cells from the spleen of immunized EAE mice were cocultured with 1×10⁴ irradiated CD4⁻ depleted splenocytes. CD4⁺CD25^hi T cells from EAE mice (Treg^EAE), NK treated EAE mice (Treg^NK-EAE) or IgG-NK treated EAE mice (Treg^IgG-NK-EAE) were added according to indicated ratios with MOG_35–55. The intensities of CFSE were determined at day 5 by FACS. CD4⁺CD25^hi Treg cells from EAE mice with IgG-NK cell treatment displayed stronger suppressive effect (p< 0.05). Mice: n = 4 per group. (<b>E</b>) Treg cells were depleted by injection of 100 µg of anti-CD25 antibody (PC61) intravenously 2 days before EAE induction. 1×10⁶ of IgG-NK cells were injected intravenously at the day of EAE induction. The mean clinical scores of EAE mice with IgG-NK cell treatment were significantly lower but it was reversed by anti-CD25 antibody treatment. Mice: n = 4 per group. Data are representative of at least 2 independent experiments and displayed as the mean ± SEM. *: p<0.05; **: p<0.01, Krusaki-Wallis test.</p