Autoantibodies in chronic lymphocytic leukemia and related systemic autoimmune diseases.
Autoantibodies in chronic lymphocytic leukemia and related systemic autoimmune diseases.
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DOI：
10.1182/blood.v81.10.2475.bloodjournal81102475
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发表时间：
1993-05
期刊：
影响因子：
20.3
通讯作者：
T. Kipps;D. Carson
中科院分区：
文献类型：
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作者：
T. Kipps;D. Carson
慢性淋巴细胞性白血病(CLL)患者的EUKEMIA B细胞常产生自身抗体。Preud‘Homme和Sig mann的早期研究表明，CLL患者的白血病细胞通常具有具有类风湿因子(RF)活性的表面IgM(SIGM)，或与人免疫球蛋白Fc部分结合的活性。在另一项有限调查中，13例患者中有4例(3.1%)的CLL细胞表达具有这种RF活性的SIgM。2用12-肉豆蔻酸酯(PMA)刺激14例CLL患者的白血病细胞分泌IgM。这些培养物中有12种(86%)能与一种或多种不同的自身抗原反应，包括免疫球蛋白、单链DNA(SsDNA)、双链DNA(DsDNA)、组蛋白、心磷脂和/或细胞骨架决定簇。Sthoeger等A14使用商陆有丝分裂原(PWM)和/或金黄色葡萄球菌Cowan菌株I(SAC)来诱导肿瘤CLL淋巴细胞分化为抗体分泌细胞。在17例CLL患者的白血病细胞培养物中，有9例(53%)具有IgM RF和/或DNA结合活性。最后，Borche et a15用23名慢性淋巴细胞性白血病患者的白血病细胞产生了异源杂交瘤。在12株CLL杂交瘤中，7株(58%)能产生足够的单抗(MOAB)，其中7株(58%)能产生IgM RF自身抗体。总的来说，这些研究表明，大多数慢性淋巴细胞性白血病患者的白血病细胞表达IgM自身抗体，最显著的是RF。自身抗体在慢性淋巴细胞性白血病中的频繁表达有何意义？如果有的话，CLL中表达的抗体类型对我们理解这种白血病的细胞遗传学和/或发病机制有什么意义？白血病B细胞产生的自身抗体与自身免疫性疾病，如自身免疫性溶血性贫血(AIHA)或免疫性血小板减少症(ITP)有什么关系？经常折磨这种疾病的患者吗？这份报告将解决这些问题中的几个，并回顾一些最近获得的关于CLL抗体表达和相关系统性自身免疫性疾病的信息。首先，回顾导致抗体多样性的机制是有帮助的。
EUKEMIA B CELLS from patients with chronic lymL phocytic leukemia (CLL) often make autoantibodies. Early studies by Preud'homme and Seligmann' showed that the leukemic cells from CLL patients often bear surface IgM (sIgM) that has rheumatoid factor (RF) activity, or binding activity for the Fc portion of human IgG. In another limited survey, the CLL cells from 4 of 13 patients (3 1 %) expressed sIgM with such RF activity.2 Using 12-myristate 13-acetate (PMA), Broker et a13 stimulated leukemia cells from 14 CLL patients to secrete IgM. Twelve (86%) of these cultures produced monoclonal IgM that reacted with one or more of a variety of different self antigens, including IgG, singlestranded DNA (ssDNA), double-stranded DNA (dsDNA), histones, cardiolipin and/or cytoskeletal determinants. Sthoeger et a14 instead used pokeweed mitogen (PWM) and/ or Staphylococcus aureus Cowan strain I (SAC) to induce neoplastic CLL lymphocytes to differentiate into antibodysecreting cells. Of the leukemia cell cultures from 17 CLL patients that had sufficient amounts of monoclonal Ig for testing, 9 (53%) had IgM RF and/or DNA-binding activity. Finally, Borche et a15 generated heterohybridomas with the leukemia cells from each of 23 CLL patients. Of the 12 CLL heterhybridomas that produced enough monoclonal antibody (MoAb) for testing, 7 (58%) produced IgM RF autoantibodies. Collectively, these studies indicate that the leukemia cells from most CLL patients express IgM autoantibodies, most notably RFs. What is the significance of the frequent expression of autoantibodies in CLL? What implications, if any, does the type of antibodies expressed in CLL have for our understanding the cytogenesis and/or etiopathogenesis of this leukemia? What relationship do the autoantibodies produced by leukemia B cells have to the autoimmune diseases, such as autoimmune hemolytic anemia (AIHA) or immune thrombocytopenia (ITP)?' that frequently afflict patients with this disease? This report will address several of these questions and review some of the recently acquired information regarding antibody expression in CLL and associated systemic autoimmune diseases. First, it is helpful to review the mechanisms that contribute to antibody diversity.