van den Berg R H, Siegert C E, Faber-Krol M C, Huizinga T W, van Es L A, Daha M R
Department of Nephrology, Leiden University Hospital, The Netherlands.
Clin Exp Immunol. 1998 Feb;111(2):359-64. doi: 10.1046/j.1365-2249.1998.00473.x.
SLE is a disease characterized by the presence of multiple autoantibodies and high levels of circulating immune complexes. We studied the presence and functional relevance of autoantibodies directed against a receptor for the collagen-like stalks of the first subcomponent of complement, also known as calreticulin (cC1qR/CaR), in patients with SLE. In a cross-sectional study it was found that higher titres of antibodies against cC1qR/CaR are present in sera of SLE patients compared with normal donors. No association between anti-cC1qR/CaR titres and SLE disease activity was found. Following gel filtration of SLE serum it was found that anti-cC1qR/CaR reactivity is associated with the peak of monomeric IgG. Purified IgG from patients was able to specifically immunoprecipitate cC1qR/CaR. Since we have shown previously that cC1qR/CaR is able to inhibit the haemolytic activity of Clq, we determined a possible pathogenic role for anti-cC1qR/CaR on complement regulation. IgG derived from SLE serum reversed the inhibitory capacity of cC1qR/CaR in a dose-dependent fashion up to 63%, whereas IgG from normal donors had no significant effect. With respect to the capacity of anti-cC1qR/CaR antibodies to activate neutrophils, it was found that incubation of normal neutrophils with F(ab')2 anti-cC1qR/CaR resulted in a very limited oxidative burst. However, cross-linking of F(ab')2 anti-cC1qR/CaR on the neutrophils clearly induced neutrophil activation. Pre-incubation of the SLE-derived F(ab')2 with cC1qR/CaR prevented activation of neutrophils up to 81+/-5%. These results suggest that the presence of anti-cC1qR/CaR antibodies in patients with SLE may modulate complement and neutrophil activation.
系统性红斑狼疮（SLE）是一种以存在多种自身抗体和高水平循环免疫复合物为特征的疾病。我们研究了系统性红斑狼疮患者中针对补体第一亚成分胶原样柄受体（也称为钙网蛋白，cC1qR/CaR）的自身抗体的存在情况及其功能相关性。在一项横断面研究中发现，与正常供体相比，SLE患者血清中抗cC1qR/CaR抗体的滴度更高。未发现抗cC1qR/CaR滴度与SLE疾病活动之间存在关联。对SLE血清进行凝胶过滤后发现，抗cC1qR/CaR反应性与单体IgG峰相关。从患者纯化的IgG能够特异性免疫沉淀cC1qR/CaR。由于我们之前已经表明cC1qR/CaR能够抑制Clq的溶血活性，因此我们确定了抗cC1qR/CaR在补体调节方面可能的致病作用。来自SLE血清的IgG以剂量依赖的方式将cC1qR/CaR的抑制能力逆转高达63%，而来自正常供体的IgG则没有显著影响。关于抗cC1qR/CaR抗体激活中性粒细胞的能力，发现用F(ab')2抗cC1qR/CaR孵育正常中性粒细胞会导致非常有限的氧化爆发。然而，F(ab')2抗cC1qR/CaR在中性粒细胞上的交联明显诱导了中性粒细胞的激活。用cC1qR/CaR对来自SLE的F(ab')2进行预孵育可使中性粒细胞的激活减少高达81±5%。这些结果表明，SLE患者中抗cC1qR/CaR抗体的存在可能调节补体和中性粒细胞的激活。
