Amoura Z, Koutouzov S, Chabre H, Cacoub P, Amoura I, Musset L, Bach J F, Piette J C
Hôpital Pitié-Salpêtrière, Paris, France.
Arthritis Rheum. 2000 Jan;43(1):76-84. doi: 10.1002/1529-0131(200001)43:1<76::AID-ANR10>3.0.CO;2-I.
To study the frequency and disease specificity of antinucleosome antibody reactivity in diverse connective tissue diseases (CTD), and to determine factors, such as antibody subclass, that may influence the pathogenicity of these antibodies in relation to disease activity.
IgG and IgM antinucleosome activities on nucleosome core particles from 496 patients with 13 different CTD and 100 patients with hepatitis C were measured by enzyme-linked immunosorbent assay (ELISA). Of the patients with CTD, 120 had systemic lupus erythematosus (SLE), 37 had scleroderma (systemic sclerosis; SSc), 20 had mixed connective tissue disease (MCTD), and 319 had other CTD, including Sjögren's syndrome, inflammatory myopathy, rheumatoid arthritis, primary antiphospholipid syndrome, Wegener's granulomatosis, Takayasu arteritis, giant cell arteritis, relapsing polychondritis, Behçet's syndrome, and sarcoidosis. Antinucleosome-positive sera were further analyzed, by isotype-specific ELISA, for antinucleosome and anti-double-stranded DNA (anti-dsDNA) IgG subclasses.
SLE, SSc, and MCTD were the only 3 CTD in which antinucleosome IgG were detected (71.7%, 45.9%, and 45.0% of patients, respectively). Antinucleosomes of the IgG3 subclass were present at high levels in patients with active SLE and were virtually absent in those with SSc, MCTD, or inactive SLE, and their levels showed a positive correlation with SLE disease activity. Of note, an increase in levels of antinucleosome of the IgG3 isotype was observed during SLE flares, and this increase was found to be closely associated with active nephritis. Levels of antinucleosome of the IgG1 subclass showed a trend toward an inverse correlation with SLE disease activity. No significant fluctuation in the anti-dsDNA isotype profile was observed in relation to SLE severity or clinical signs.
Our data suggest that IgG antinucleosome is a new marker that may help in the differential diagnosis of CTD; antinucleosome of the IgG3 isotype might constitute a selective biologic marker of active SLE, in particular, of lupus nephritis.
研究不同结缔组织病（CTD）中抗核小体抗体反应性的频率和疾病特异性，并确定可能影响这些抗体与疾病活动相关致病性的因素，如抗体亚类。
采用酶联免疫吸附测定（ELISA）法检测496例患有13种不同CTD的患者和100例丙型肝炎患者的核小体核心颗粒上的IgG和IgM抗核小体活性。在患有CTD的患者中，120例患有系统性红斑狼疮（SLE），37例患有硬皮病（系统性硬化症；SSc），20例患有混合性结缔组织病（MCTD），319例患有其他CTD，包括干燥综合征、炎性肌病、类风湿关节炎、原发性抗磷脂综合征、韦格纳肉芽肿病、高安动脉炎、巨细胞动脉炎、复发性多软骨炎、白塞病和结节病。通过同型特异性ELISA对抗核小体阳性血清进一步分析抗核小体和抗双链DNA（抗dsDNA）IgG亚类。
SLE、SSc和MCTD是仅有的3种检测到抗核小体IgG的CTD（分别占患者的71.7%、45.9%和45.0%）。IgG3亚类的抗核小体在活动期SLE患者中高水平存在，而在SSc、MCTD或非活动期SLE患者中几乎不存在，其水平与SLE疾病活动呈正相关。值得注意的是，在SLE病情发作期间观察到IgG3同型抗核小体水平升高，并且发现这种升高与活动性肾炎密切相关。IgG1亚类抗核小体水平与SLE疾病活动呈负相关趋势。未观察到抗dsDNA同型谱与SLE严重程度或临床体征有显著波动。
我们的数据表明，IgG抗核小体是一种可能有助于CTD鉴别诊断的新标志物；IgG3同型抗核小体可能构成活动期SLE尤其是狼疮性肾炎的选择性生物学标志物。
