Objective To recover broad-neutralizing monoclonal antibodies(Bn Abs)from avian influenza A(H5N1)virus infection cases and investigate their genetic and functional features.Methods We screened the Abs repertoires of e...Objective To recover broad-neutralizing monoclonal antibodies(Bn Abs)from avian influenza A(H5N1)virus infection cases and investigate their genetic and functional features.Methods We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of H5N1 patients.The genetic basis,biological functions,and epitopes of the obtained Bn Abs were assessed and modeled.Results Two Bn Abs,2-12 D5,and 3-37 G7.1,were respectively obtained from two human H5N1 cases on days 12 and 21 after disease onset.Both Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity(ADCC)activity.Albeit derived from distinct Ab lineages,i.e.,V^H1-69-D2-15-JH^4(2-12D5)and V^H1-2-D3-9-JH^5(3-32 G7.1),the Bn Abs were directed toward CR6261-like epitopes in the HA stem,and HA2 I45 in the hydrophobic pocket was the critical residue for their binding.Signature motifs for binding with the HA stem,namely,IFY in VH1-69-encoded Abs and LXYFXW in D3-9-encoded Abs,were also observed in 2-12D5 and 3-32 G7.1,respectively.Conclusions Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza virus.The HA stem epitopes targeted by the Bn Abs,and the two Ab-encoding genes usage implied the VH1-69 and D3-9 are the ideal candidates triggered by influenza virus for vaccine development.展开更多
Objective The study will explore effects of the autoantibodies against AT1 receptor and angiotensin Ⅱ on the refractory hypertension. Methods Seventy-seven patients (46 men and 31 women) with essential hypertension w...Objective The study will explore effects of the autoantibodies against AT1 receptor and angiotensin Ⅱ on the refractory hypertension. Methods Seventy-seven patients (46 men and 31 women) with essential hypertension were divided into groups of refractory hypertension (RH) and hypertension (HT) according to the 1999 WHO-ISH Guidelines for the Management of Hypertension. Forty normotensives (22 men) were recruited as controls. The mean age was 54. 3±13 years old in RH group, 53. 5±9 years old in HT group and 51. 2±11. 9 years old in normotensives (NT) group. The mean blood pressure was 154. 2±9. 4/98. 4± 8. 2 mmHg in RH group and 130. 1±7. 6/80. 5±6. 7 mmHg in HT group after combination drug therapy of hypertension for 4 weeks. Blood pressure in NT group was 120. 8±11. 7/76. 4 ± 7. 2 mmHg. The epitope of the 2nd extracellular loops of AT1 receptor was synthesized and used as antigens to screen the autoantibodies by ELISA. Plasma angiotensin (Ang) II were examined by a radioimmunoassay. Results The autoantibodies against AT1 receptor were positive in 18 (46. 15 %) patients with RH, in 4 (10. 5 % ) hypertension and in 3 (7. 5 % ) normotensives, P < 0. 01. Ang Ⅱwas 57. 01±52. 63 pmol/L in patients with RH. Both the autoantibodies positive and the Ang Ⅱ increasing were 4 (10. 3 % ) cases, both normal were 7 (17. 9 % ) cases, the autoantibodies positive or Ang II increasing was all of 14 (35. 9 % ) cases (x2 = 0. 09, P>0. 05) . There was no relationship between the autoantibodies against AT1 receptor and the angiotensin Ⅱ in refractory hypertension. Conclusion The autoantibodies against AT1 receptor and Ang Ⅱ might be two independent factors in developing of refractory hypertension. The findings suggest that AT1 receptor an-tagnist used in the treatment of refractory hypertension might have an important value.展开更多
基金supported by the General Program of the National Natural Science Foundation of China[No.31570162]the National Key Research Program[No.2016YFC1200200].
文摘Objective To recover broad-neutralizing monoclonal antibodies(Bn Abs)from avian influenza A(H5N1)virus infection cases and investigate their genetic and functional features.Methods We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of H5N1 patients.The genetic basis,biological functions,and epitopes of the obtained Bn Abs were assessed and modeled.Results Two Bn Abs,2-12 D5,and 3-37 G7.1,were respectively obtained from two human H5N1 cases on days 12 and 21 after disease onset.Both Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity(ADCC)activity.Albeit derived from distinct Ab lineages,i.e.,V^H1-69-D2-15-JH^4(2-12D5)and V^H1-2-D3-9-JH^5(3-32 G7.1),the Bn Abs were directed toward CR6261-like epitopes in the HA stem,and HA2 I45 in the hydrophobic pocket was the critical residue for their binding.Signature motifs for binding with the HA stem,namely,IFY in VH1-69-encoded Abs and LXYFXW in D3-9-encoded Abs,were also observed in 2-12D5 and 3-32 G7.1,respectively.Conclusions Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza virus.The HA stem epitopes targeted by the Bn Abs,and the two Ab-encoding genes usage implied the VH1-69 and D3-9 are the ideal candidates triggered by influenza virus for vaccine development.
文摘Objective The study will explore effects of the autoantibodies against AT1 receptor and angiotensin Ⅱ on the refractory hypertension. Methods Seventy-seven patients (46 men and 31 women) with essential hypertension were divided into groups of refractory hypertension (RH) and hypertension (HT) according to the 1999 WHO-ISH Guidelines for the Management of Hypertension. Forty normotensives (22 men) were recruited as controls. The mean age was 54. 3±13 years old in RH group, 53. 5±9 years old in HT group and 51. 2±11. 9 years old in normotensives (NT) group. The mean blood pressure was 154. 2±9. 4/98. 4± 8. 2 mmHg in RH group and 130. 1±7. 6/80. 5±6. 7 mmHg in HT group after combination drug therapy of hypertension for 4 weeks. Blood pressure in NT group was 120. 8±11. 7/76. 4 ± 7. 2 mmHg. The epitope of the 2nd extracellular loops of AT1 receptor was synthesized and used as antigens to screen the autoantibodies by ELISA. Plasma angiotensin (Ang) II were examined by a radioimmunoassay. Results The autoantibodies against AT1 receptor were positive in 18 (46. 15 %) patients with RH, in 4 (10. 5 % ) hypertension and in 3 (7. 5 % ) normotensives, P < 0. 01. Ang Ⅱwas 57. 01±52. 63 pmol/L in patients with RH. Both the autoantibodies positive and the Ang Ⅱ increasing were 4 (10. 3 % ) cases, both normal were 7 (17. 9 % ) cases, the autoantibodies positive or Ang II increasing was all of 14 (35. 9 % ) cases (x2 = 0. 09, P>0. 05) . There was no relationship between the autoantibodies against AT1 receptor and the angiotensin Ⅱ in refractory hypertension. Conclusion The autoantibodies against AT1 receptor and Ang Ⅱ might be two independent factors in developing of refractory hypertension. The findings suggest that AT1 receptor an-tagnist used in the treatment of refractory hypertension might have an important value.
