Amore A, Coppo R, Nedrud J G, Sigmund N, Lamm M E, Emancipator S N
Department of Nephrology and Dialysis, Regina Margherita Hospital, Turin, Italy.
Clin Immunol. 2004 Oct;113(1):101-8. doi: 10.1016/j.clim.2004.06.002.
Mucosal antigenic exposure is implicated in pathogenesis of IgA nephropathy. Although IgG and/or IgM codeposits may promote disease, protracted mucosal antigenic exposure reduces IgG and IgM antibody, a process termed mucosal tolerance. We immunized mice intranasally with infectious or inactivated Sendai virus for 6 or 14 weeks. Anti-virus IgG remained high in mice given infectious virus for 14 weeks, but decreased after 6 weeks in mice given inactivated virus; IgA antibody remained high in both groups. Upon viral challenge, glomerular IgG and complement deposits and the frequency of hematuria, all equal after 6 weeks of immunization, were lower in mice immunized with inactivated virus for 14 weeks but remained high in mice given infectious virus; glomerular IgA increased over time in both immunized groups. Viremia in a non-tolerized immune host can promote glomerulonephritis with IgG and complement codeposits and glomerular dysfunction. These preliminary experiments may guide future, more mechanistic, investigation.
黏膜抗原暴露与IgA肾病的发病机制有关。虽然IgG和/或IgM共沉积可能会促进疾病发展，但长期的黏膜抗原暴露会降低IgG和IgM抗体水平，这一过程称为黏膜耐受。我们用感染性或灭活的仙台病毒对小鼠进行鼻内免疫，持续6周或14周。接受感染性病毒免疫14周的小鼠体内抗病毒IgG水平仍然很高，但接受灭活病毒免疫6周后的小鼠体内该抗体水平下降；两组小鼠体内的IgA抗体水平均保持较高。在病毒攻击后，免疫6周后肾小球IgG和补体沉积以及血尿频率均相同，但接受灭活病毒免疫14周的小鼠体内这些指标较低，而接受感染性病毒免疫的小鼠体内则仍然较高；两个免疫组的肾小球IgA均随时间增加。未耐受免疫宿主中的病毒血症可促进伴有IgG和补体共沉积以及肾小球功能障碍的肾小球肾炎。这些初步实验可能会为未来更具机制性的研究提供指导。
