Kourtis A P, Boussiotis V A, Lymberi P, Pangalis G A
Department of Immunology, Hellenic Pasteur Institute, University of Athens School of Medicine, Laikon General Hospital, Athens, Greece.
Am J Hematol. 1994 Aug;46(4):283-8. doi: 10.1002/ajh.2830460406.
In view of the frequent association between malignant lymphoproliferative diseases and autoimmunity, we studied by ELISA the presence, isotype, and specificity of natural antibodies in sera from 60 patients with malignant non-Hodgkin's lymphomas and 70 healthy controls. The antigens selected were actin, tubulin, myosin, troponin, tropomyosin, keratin, thyroglobulin, single stranded DNA, and the hapten trinitrophenyl. The results of this study were compared with the presence of oligoclonal immunoglobulins in the same sera, as previously detected by Isoelectric Focusing and Immunoblotting. Our results showed that 1) there is a high proportion of autoreactive NHL sera: 28 (46.6%) exhibited high IgG natural antibody activity (Nab) against one or more panel antigens, mostly against keratin, myosin, and tropomyosin, 26 (43.3%) had high IgA Nab activity, mainly against myosin, keratin, and ssDNA, whereas 17 (28.3%) displayed a high IgM Nab activity. The great majority (> 80%) of positive sera was polyspecific, i.e., reacted with at least two panel antigens. 2) A strong correlation exists between the high serum Nab activity and the presence of paraproteins: of the 28 sera exhibiting high IgG Nab activity, 16 (57%) contained oligoclonal IgG, and of the 17 sera exhibiting high IgM Nab activity, 13 (76.4%) contained oligoclonal IgM. The Nabs detected had frequently the same heavy and light chain as the paraproteins. No relationship between the presence of paraproteins with Nab activity and the stage of disease or grade of malignancy was found. We conclude that the high incidence of clonal immunoglobulins of different isotypes with various autoantibody specificities suggests an oligoclonal lymphocyte activation involving Nab producing cells. The significance of such autoreactive clones in NHL patients remains to be elucidated.
鉴于恶性淋巴增殖性疾病与自身免疫之间频繁关联，我们通过酶联免疫吸附测定（ELISA）研究了60例恶性非霍奇金淋巴瘤患者和70名健康对照者血清中天然抗体的存在情况、同种型及特异性。所选抗原为肌动蛋白、微管蛋白、肌球蛋白、肌钙蛋白、原肌球蛋白、角蛋白、甲状腺球蛋白、单链DNA以及半抗原三硝基苯。本研究结果与之前通过等电聚焦和免疫印迹法检测到的相同血清中寡克隆免疫球蛋白的存在情况进行了比较。我们的结果表明：1）存在高比例的自身反应性非霍奇金淋巴瘤血清：28例（46.6%）表现出针对一种或多种组抗原的高IgG天然抗体活性（Nab），主要针对角蛋白、肌球蛋白和原肌球蛋白；26例（43.3%）具有高IgA Nab活性，主要针对肌球蛋白、角蛋白和单链DNA，而17例（28.3%）表现出高IgM Nab活性。绝大多数（>80%）阳性血清是多特异性的，即与至少两种组抗原发生反应。2）高血清Nab活性与副蛋白的存在之间存在强烈相关性：在表现出高IgG Nab活性的28例血清中，16例（57%）含有寡克隆IgG；在表现出高IgM Nab活性的17例血清中，13例（76.4%）含有寡克隆IgM。检测到的Nab通常与副蛋白具有相同的重链和轻链。未发现副蛋白与Nab活性的存在与疾病分期或恶性程度之间存在关联。我们得出结论，不同同种型且具有各种自身抗体特异性的克隆免疫球蛋白的高发生率表明涉及产生Nab的细胞的寡克隆淋巴细胞活化。此类自身反应性克隆在非霍奇金淋巴瘤患者中的意义仍有待阐明。
