Skattum L, Akesson P, Truedsson L, Sjöholm A G
Section of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Lund, Sweden.
Int Arch Allergy Immunol. 2006;140(1):9-19. doi: 10.1159/000091745. Epub 2006 Feb 27.
Responses against antigens from the potentially nephritogenic Streptococcus pyogenes serotype M1 in patients with acute poststreptococcal glomerulonephritis (AGN) were studied to seek indications of expression of these antigens during the preceding infection. Also, the question was asked whether the complement protein mannan-binding lectin (MBL) is required for development of the hypocomplementemia associated with AGN. Hypothetically, the lectin pathway might trigger the alternative pathway, which is consistently activated in AGN.
Antibodies against three proteins associated with M1, M1 protein, streptococcal inhibitor of complement (SIC) and protein H, an IgG-binding protein, were determined by ELISA in 56 children and 17 adults with AGN. Antibodies against streptococcal cysteine proteinase, which is produced by all serotypes of S. pyogenes, were also examined. MBL concentrations were measured in the same 71 patients by a sandwich ELISA.
Increased concentrations of antibodies were found against all four streptococcal proteins, albeit not uniformly distributed between different subgroups of patients. The prevalence of low MBL concentrations (<100 microg/l) including 2 patients with undetectable MBL (<10 microg/l) was similar in AGN (11%) and in controls (16%).
Our results give evidence of exposure to SIC and protein H in conjunction with AGN. This implies that SIC and protein H and/or cross-reacting proteins may have a role in the pathogenesis of AGN or that streptococci expressing SIC or protein H are nephritogenic for other reasons. The finding of MBL-deficient individuals among the patients demonstrates that MBL is not necessary for the recruitment of complement in AGN.
对急性链球菌感染后肾小球肾炎(AGN)患者针对潜在致肾炎性化脓性链球菌M1血清型抗原的反应进行了研究,以寻找这些抗原在先前感染期间表达的迹象。此外,还提出了补体蛋白甘露聚糖结合凝集素(MBL)是否是AGN相关低补体血症发生所必需的问题。假设凝集素途径可能触发替代途径,而替代途径在AGN中持续被激活。
通过酶联免疫吸附测定(ELISA)法,对56名儿童和17名成人AGN患者检测了针对与M1相关的三种蛋白(M1蛋白、链球菌补体抑制剂(SIC)和IgG结合蛋白H)的抗体。还检测了针对化脓性链球菌所有血清型产生的链球菌半胱氨酸蛋白酶的抗体。通过夹心ELISA法测定了同一71名患者的MBL浓度。
发现针对所有四种链球菌蛋白的抗体浓度均升高,尽管在不同患者亚组中分布并不均匀。AGN患者(11%)和对照组(16%)中低MBL浓度(<100μg/l)包括2例MBL检测不到(<10μg/l)患者的患病率相似。
我们的结果证明AGN患者接触过SIC和蛋白H。这意味着SIC和蛋白H及/或交叉反应蛋白可能在AGN发病机制中起作用,或者表达SIC或蛋白H的链球菌因其他原因具有致肾炎性。在患者中发现MBL缺乏个体表明MBL并非AGN中补体募集所必需。