Axford J S, Watts R A, Long A A, Isenberg D A, Steere A C
Academic Rheumatology Unit, St George's Hospital Medical School, London, United Kingdom.
Ann Rheum Dis. 1993 Mar;52(3):199-205. doi: 10.1136/ard.52.3.199.
Joints are often affected in Lyme disease and in some instances this may be due to immune autoreactivity. To characterise further the immune response in this disease investigations were carried out to determine the expression of three public idiotypes on serum immunoglobulins in patients with Lyme disease during the development of varying degrees of arthritis.
The expression of idiotypes (Ids) 16/6, BEG2, and PR4, first identified on monoclonal antibodies to DNA, was determined by an enzyme linked immunosorbent assay (ELISA) in serial blood samples from 12 patients with Lyme disease over a mean period of six years during the development of a variety of arthritic symptoms, and in serum samples from healthy control subjects and control subjects with systemic lupus erythematosus.
Expression of serum IgM or IgG public Ids 16/6 and BEG2 was significantly increased in patients with Lyme disease. IgA Id 16/6 expression, in contrast, was significantly increased only during episodes of arthritis and was also related to its severity. IgM and IgG Id 16/6 expression was related to their respective total immunoglobulin concentration and, in the case of IgM, to the level of IgM antibodies to Borrelia burgdorferi, whereas similar findings were not apparent with IgA antibodies. This may indicate that the IgA response is related to the pathogenesis of arthritis, especially as total IgA and IgA Id 16/6 levels were found to increase over the duration of disease. Sequential analysis of antibodies also showed restriction in the expression of Id 16/6 as it was never found on all immunoglobulin isotypes at the same time, and Id PR4 was never expressed. Ids 16/6 and BEG2 expression, however, may be associated as seven patients expressed these idiotypes simultaneously.
These data indicate the use of public idiotypes in the immune response against B burgdorferi, which may be restricted in terms of idiotype class and isotype expression, and a possible association between IgA antibodies bearing Id 16/6 with arthritis.
莱姆病常累及关节,在某些情况下这可能归因于免疫自身反应性。为了进一步明确该疾病中的免疫反应,开展了相关研究,以确定不同程度关节炎发展过程中莱姆病患者血清免疫球蛋白上三种公共独特型的表达情况。
通过酶联免疫吸附测定(ELISA),对12例莱姆病患者在平均6年的时间里出现各种关节炎症状时的系列血样,以及健康对照者和系统性红斑狼疮对照者的血清样本,测定最初在抗DNA单克隆抗体上鉴定出的独特型(Id)16/6、BEG2和PR4的表达。
莱姆病患者血清IgM或IgG公共独特型16/6和BEG2的表达显著增加。相比之下,IgA独特型16/6的表达仅在关节炎发作期间显著增加,且与关节炎的严重程度相关。IgM和IgG独特型16/6的表达与其各自的总免疫球蛋白浓度相关,就IgM而言,还与抗伯氏疏螺旋体IgM抗体水平相关,而IgA抗体则未出现类似结果。这可能表明IgA反应与关节炎的发病机制有关,尤其是因为发现总IgA和IgA独特型16/6水平在疾病过程中会升高。抗体的序列分析还显示独特型16/6的表达具有限制性,因为它从未同时出现在所有免疫球蛋白同种型上,且独特型PR4从未表达。然而,独特型16/6和BEG2的表达可能存在关联,因为有7例患者同时表达了这些独特型。
这些数据表明公共独特型在针对伯氏疏螺旋体的免疫反应中的应用,其在独特型类别和同种型表达方面可能受到限制,以及携带独特型16/6的IgA抗体与关节炎之间可能存在关联。