Shokri F, Mageed R A, Kitas G D, Katsikis P, Moutsopoulos H M, Jefferis R
Department of Immunology, University of Birmingham Medical School, England.
Clin Exp Immunol. 1991 Jul;85(1):20-7. doi: 10.1111/j.1365-2249.1991.tb05676.x.
The aetiology of sustained autoantibody production in human autoimmune diseases is unknown. Evidence for structural similarities and common clonal origin among autoantibodies have been demonstrated through the expression of cross-reactive idiotype (CRI). In the present study we use four monoclonal antibodies (MoAbs) with specificity for non-overlapping CRI on human rheumatoid factor (RF) autoantibodies to define the structural features of polyclonal RF characteristic of patients with autoimmune rheumatic diseases. The pattern of CRI expression in the serum of 12 patients with rheumatoid arthritis (RA), eight with systemic lupus erythematosus (SLE) and 20 with primary Sjögren's syndrome and 34 normal individuals were determined in parallel with the level of IgM RF, IgA RF and autoantibodies to the cellular antigens SS-A, SS-B, Sm, nRNP and dsDNA and cryoglobulins. The results demonstrate significant elevation in the level of IgM and IgA expressing VHI (G6 and G8) and VHIII (B6 and D12) associated CRI in the serum of patients with autoimmune rheumatic diseases compared with normal individuals. These increases paralleled, but did not equal the increase in the level of immunoglobulins and RF. However, when expressed as proportion of immunoglobulin, only the VHI-associated CRI were significantly elevated in patients compared with normal individuals. The proportion of IgM RF expressing the VHI-associated CRI was higher in patients with Sjögren's syndrome compared with SLE and RA. Furthermore, the proportion of IgA RF expressing the G6 CRI was higher than G6+ IgM RF. These findings imply that different mechanisms contribute to RF production in autoimmune diseases. It is suggested that polyconal B cell activation is likely to be a contributing mechanism. However, such polyclonal activation is unlikely to be random since a selective elevation in the level of specific autoantibodies and VHI-associated CRI is observed. Furthermore, the data demonstrate that a proportion of autoantibodies in autoimmune diseases are immunoglobulin germline gene encoded. This is more evident in some patients with primary Sjögren's syndrome, where RF is likely to be oligoclonal or monoclonal in individuals with lymphoproliferation.
人类自身免疫性疾病中持续性自身抗体产生的病因尚不清楚。通过交叉反应独特型（CRI）的表达，已证明自身抗体之间存在结构相似性和共同的克隆起源。在本研究中，我们使用四种对人类类风湿因子（RF）自身抗体上非重叠CRI具有特异性的单克隆抗体（MoAb），来确定自身免疫性风湿性疾病患者多克隆RF的结构特征。同时测定了12例类风湿关节炎（RA）患者、8例系统性红斑狼疮（SLE）患者、20例原发性干燥综合征患者和34例正常个体血清中CRI的表达模式，以及IgM RF、IgA RF和针对细胞抗原SS - A、SS - B、Sm、nRNP和dsDNA的自身抗体水平和冷球蛋白水平。结果表明，与正常个体相比，自身免疫性风湿性疾病患者血清中表达VHI（G6和G8）和VHIII（B6和D12）相关CRI的IgM和IgA水平显著升高。这些升高与免疫球蛋白和RF水平的升高平行，但并不相等。然而，当以免疫球蛋白的比例表示时，与正常个体相比，患者中仅VHI相关的CRI显著升高。干燥综合征患者中表达VHI相关CRI的IgM RF比例高于SLE和RA患者。此外，表达G6 CRI的IgA RF比例高于G6 + IgM RF。这些发现意味着不同的机制参与了自身免疫性疾病中RF的产生。提示多克隆B细胞活化可能是一个促成机制。然而，这种多克隆活化不太可能是随机的，因为观察到特定自身抗体和VHI相关CRI水平有选择性升高。此外，数据表明自身免疫性疾病中的一部分自身抗体是由免疫球蛋白种系基因编码的。这在一些原发性干燥综合征患者中更为明显，在这些患者中，RF在有淋巴细胞增殖的个体中可能是寡克隆或单克隆的。
