Fracchiolla N S, Barcellini W, Bianchi P, Motta M, Fermo E, Cortelezzi A
Dipartimento di Ematologia, Ospedale Maggiore Policlinico IRCCS, Vis F. Sforza 35, 20122-Milan, Italy.
Br J Haematol. 2001 Mar;112(4):969-71. doi: 10.1046/j.1365-2141.2001.02677.x.
Campath-1H, an anti-CD52 monoclonal antibody, is therapeutically active in lymphoproliferative and autoimmune diseases. After Campath-1H therapy, lymphocytes with a paroxysmal nocturnal haemoglobinuria (PNH) phenotype have been reported to emerge. We characterized a PNH-like lymphocyte population emerging after Campath-1H therapy, in a patient with fludarabine refractory B-cell chronic lymphocytic leukaemia (B-CLL). We demonstrated a reduction in PIG-A mRNA levels compared with controls, and of all cytokines tested [interleukin (IL)-4, IL-13, IL-2, interferon(IFN)-gamma, IL-6, IL-10, and tumour necrosis factor (TNF)-alpha], except transforming growth factor (TGF)-beta. Given the inhibitory activity of TGF-beta, its elevated levels may contribute to the selective pressure of Campath-1H, leading to the emergence of PNH-like lymphocytes.
Campath-1H是一种抗CD52单克隆抗体，在淋巴增殖性疾病和自身免疫性疾病的治疗中具有活性。据报道，在接受Campath-1H治疗后，会出现具有阵发性夜间血红蛋白尿（PNH）表型的淋巴细胞。我们对一名氟达拉滨难治性B细胞慢性淋巴细胞白血病（B-CLL）患者在接受Campath-1H治疗后出现的类似PNH的淋巴细胞群体进行了表征。与对照组相比，我们发现PIG-A mRNA水平降低，并且在所有检测的细胞因子[白细胞介素（IL）-4、IL-13、IL-2、干扰素（IFN）-γ、IL-6、IL-10和肿瘤坏死因子（TNF）-α]中，除了转化生长因子（TGF）-β外，其他细胞因子水平均降低。鉴于TGF-β的抑制活性，其水平升高可能导致Campath-1H的选择性压力，从而导致类似PNH的淋巴细胞出现。
