Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Department of Clinical Laboratory Investigation, Graduate School of Medicine, Shinshu University, Matsumoto, Japan.
Int J Hematol. 2020 Jul;112(1):96-104. doi: 10.1007/s12185-020-02874-1. Epub 2020 Apr 6.
We report a case of acquired dysfibrinogenemia with monoclonal gammopathy of undetermined significance presenting λ-type IgA M protein. The patient showed lower functional (0.4 g/dL) and normal immunological fibrinogen (2.9 g/dL). To examine the cause of the false lower value of fibrinogen, we performed experiments using the patient's purified fibrinogen and IgA. Fibrinogen was purified from the patient's plasma; IgA was purified from plasma or serum by immunoaffinity chromatography. We performed thrombin-catalyzed fibrin polymerization, scanning electron microscopy (SEM), immunoblotting analysis, and enzyme-linked immunosorbent assays (ELISAs). Fibrin polymerization in the patient's plasma was markedly reduced and SEM showed no fiber bundles or sponge-like structures. Purified IgA did not influence polymerization, whereas immunoprecipitated plasma with an anti-IgA (α-chain) antibody indicated normalization of polymerization and clot structure. Western blotting analysis revealed the presence of monoclonal λ-type IgA-bound fibrinogen, the proportion of which was significantly higher than normal control plasma using ELISA. Our results suggest that IgA M protein-bound fibrinogen is not normally converted into fibrin, but rather leads to formation of an aberrantly structured fragile clot. The patient's reduced plasma fibrinogen level was caused by the presence of IgA M protein-bound fibrinogen, not by IgA M protein alone.
我们报告了一例伴有单克隆免疫球蛋白增多症未定型的获得性纤维蛋白原血症，其为 λ 型 IgA M 蛋白。患者表现出较低的功能性纤维蛋白原（0.4 g/dL）和正常的免疫性纤维蛋白原（2.9 g/dL）。为了研究纤维蛋白原假性低值的原因，我们使用患者纯化的纤维蛋白原和 IgA 进行了实验。从患者的血浆中纯化纤维蛋白原；通过免疫亲和层析从血浆或血清中纯化 IgA。我们进行了凝血酶催化的纤维蛋白聚合、扫描电子显微镜（SEM）、免疫印迹分析和酶联免疫吸附测定（ELISA）。患者血浆中的纤维蛋白聚合明显减少，SEM 显示无纤维束或海绵样结构。纯化的 IgA 不影响聚合，而用抗 IgA（α 链）抗体免疫沉淀的血浆表明聚合和凝块结构正常化。Western blot 分析显示存在单克隆 λ 型 IgA 结合纤维蛋白原，其比例用 ELISA 检测明显高于正常对照血浆。我们的结果表明，IgA M 蛋白结合的纤维蛋白原不能正常转化为纤维蛋白，而是导致形成异常结构的脆弱凝块。患者血浆纤维蛋白原水平降低是由于存在 IgA M 蛋白结合的纤维蛋白原，而不是单独的 IgA M 蛋白。
