Woolley P V, Sacher R A, Priego V M, Schanfield M S, Bonnem E M
Br J Haematol. 1983 Aug;54(4):543-52. doi: 10.1111/j.1365-2141.1983.tb02132.x.
A woman with metastatic breast carcinoma developed acute haemolytic anaemia on two occasions following treatment with methotrexate (MTX) and 5-fluorouracil (5-FU). The direct antiglobulin test was positive. Compatible control cells were pretreated with either MTX or 5-FU and subsequently incubated with patient and control sera. Agglutination in the indirect antiglobulin test was observed only in the presence of patient serum and MTX, and did not occur following pretreatment with 5-FU, folic acid, folinic acid or triamterene. There was no evidence of complement binding to the red cell surface. A macrophage assay showed increased phagocytic uptake of MTX-treated cells in the presence of patient serum. This phagocytosis was not enhanced by the addition of complement. The antibody subclass was predominantly IgG-3. The 51Cr red cell survival of autologous MTX cells was markedly shortened, indicating rapid in vivo destruction. These studies demonstrate the occurrence of acute haemolytic anaemia due to an IgG-3 antibody that reacts with erythrocytes in the presence of methotrexate. This antibody does not fix complement, but sensitizes red blood cells to phagocytosis by macrophages.
一名转移性乳腺癌女性在接受甲氨蝶呤（MTX）和5-氟尿嘧啶（5-FU）治疗后两次发生急性溶血性贫血。直接抗球蛋白试验呈阳性。将相容的对照细胞用MTX或5-FU预处理，随后与患者血清和对照血清一起孵育。间接抗球蛋白试验中的凝集仅在患者血清和MTX存在时观察到，在用5-FU、叶酸、亚叶酸或氨苯蝶啶预处理后未发生。没有证据表明补体与红细胞表面结合。巨噬细胞试验显示在患者血清存在下，MTX处理的细胞吞噬摄取增加。添加补体并不能增强这种吞噬作用。抗体亚类主要为IgG-3。自体MTX细胞的51Cr红细胞存活期明显缩短，表明体内快速破坏。这些研究证明了由于IgG-3抗体在甲氨蝶呤存在下与红细胞反应而发生急性溶血性贫血。这种抗体不固定补体，但使红细胞对巨噬细胞的吞噬作用敏感。
