Mårtensson U, Sjöholm A G, Sturfelt G, Truedsson L, Laurell A B
Department of Medical Microbiology, Lund University, Sweden.
Scand J Immunol. 1992 Jun;35(6):735-44. doi: 10.1111/j.1365-3083.1992.tb02982.x.
An enzyme-linked immunosorbent assay (ELISA) with purified collagenous C1q fragments in the solid phase was used for detection of C1q-specific immunoglobulins in the sera of twelve patients with systemic lupus erythematosus (SLE) or the SLE-like disease hypocomplementemic urticarial vasculitis syndrome (HUVS). By clinical criteria, four patients had SLE, and three HUVS. Five patients had overlap syndromes. All patients demonstrated high concentrations of C1q-specific IgG and markedly low concentrations of circulating C1q. Detection of C1q-specific IgG in SLE sera was facilitated by employment of saturating concentrations of collagenous C1q fragments in the solid-phase ELISA. When added to SLE serum, immune complex-fixed C1q inhibited binding of IgG to the C1q fragments, whereas addition of C1q alone had limited inhibitory effects. Under similar conditions, using approximately equimolar amounts of C1q relative to solid-phase C1q fragments, no ELISA inhibition was obtained after addition of C1q or immune complex-fixed C1q to a HUVS serum. Even in large excess, purified C1q did not inhibit binding of HUVS-IgG to solid-phase C1q fragments. Thus, possible interactions between HUVS-IgG and native Clq are probably of low affinity. By Western blot analysis, IgG reactive with the B and C chains of C1q was found in the eight patients with evidence of HUVS, five of whom also showed IgG binding to C'-C' and A'-B' dimers of collagenous C1q fragments. Sera from SLE patients were negative by Western blot analysis. It seems likely that C1q-specific IgG in SLE primarily recognizes assembled C1q molecules or collagenous C1q fragments expressing conformational epitopes of bound C1q. Interestingly, patients with evidence of HUVS fairly consistently had zymogen (C1r-C1s)2 complexes in their serum, while patients with SLE showed high concentrations of complexes containing Cl inhibitor, C1r and C1s. Different binding specificities of C1q-reactive IgG could be of importance with regard to pathogenetic mechanisms in SLE and HUVS. There was no correlation between findings of C1q-specific IgG and a variety of autoantibodies associated with SLE and SLE-like disease.
采用固相含有纯化胶原性C1q片段的酶联免疫吸附测定（ELISA）法，检测12例系统性红斑狼疮（SLE）患者或SLE样疾病低补体血症性荨麻疹性血管炎综合征（HUVS）患者血清中的C1q特异性免疫球蛋白。根据临床标准，4例患者患有SLE，3例患有HUVS。5例患者有重叠综合征。所有患者均显示C1q特异性IgG浓度高，循环C1q浓度显著低。在固相ELISA中使用饱和浓度的胶原性C1q片段有助于检测SLE血清中的C1q特异性IgG。当加入SLE血清时，免疫复合物固定的C1q可抑制IgG与C1q片段的结合，而单独加入C1q的抑制作用有限。在类似条件下，相对于固相C1q片段使用大约等摩尔量的C1q，向HUVS血清中加入C1q或免疫复合物固定的C1q后未获得ELISA抑制。即使大量过量，纯化的C1q也不能抑制HUVS-IgG与固相C1q片段的结合。因此，HUVS-IgG与天然C1q之间可能的相互作用亲和力可能较低。通过蛋白质印迹分析，在8例有HUVS证据的患者中发现了与C1q的B链和C链反应的IgG，其中5例还显示IgG与胶原性C1q片段的C'-C'和A'-B'二聚体结合。SLE患者的血清经蛋白质印迹分析为阴性。看来SLE中的C1q特异性IgG主要识别组装好的C1q分子或表达结合C1q构象表位的胶原性C1q片段。有趣的是，有HUVS证据的患者血清中相当一致地存在酶原（C1r-C1s）2复合物，而SLE患者显示含有C1抑制剂、C1r和C1s的复合物浓度高。C1q反应性IgG的不同结合特异性可能在SLE和HUVS的发病机制方面具有重要意义。C1q特异性IgG的检测结果与多种与SLE和SLE样疾病相关的自身抗体之间无相关性。
