Varga Lilian, Széplaki Gábor, Visy Beáta, Füst George, Harmat George, Miklós Katalin, Németh Julianna, Cervenak László, Karádi István, Farkas Henriette
3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi 4, H-1125 Budapest, Hungary.
Mol Immunol. 2007 Feb;44(6):1454-60. doi: 10.1016/j.molimm.2006.04.020. Epub 2006 Jun 5.
The presence of autoantibodies to C1-inhibitor (C1-INH-Abs) is a hallmark of acquired C1-inhibitor deficiency. However, only scarce data are available on their prevalence in hereditary angioedema (HAE). In a prospective study performed between 2001 and 2004 in 95 patients with Type I or II HAE, serum samples were taken one to three times a year and clinical status of the patients was registered. Serum samples were tested for total activity of the classical pathway, C1q, C3, C4 and C1-inhibitor (C1-INH) concentration and activity levels, as well as the presence of IgG, IgA and IgM type anti-C1-inhibitor antibodies (C1-INH-Ab). Fifty-four healthy age and gender matched persons served as control. Significant differences between the patients and controls in the occurrence of elevated (2S.D. higher than mean of control) C1-INH-Abs titers was found only in the case of IgM type C1-INH-Abs. Elevated (>4.22AU/ml) IgM C1-INH-Abs levels were found in 31 and 4% of the patients and controls, respectively (p<0.001). Surprisingly, high titer IgM C1-INH-Abs were present with equal frequency in the 41 HAE patients ever treated with C1-INH concentrate and in the 54 C1-INH treatment naïve patients. In the latter group, strong positive correlation between the levels of the IgM C1-INH-Abs and the most severe disease (score 1) (p=0.0021) and the yearly attack rate (p=0.0173) were obtained. In addition, the levels of the IgM C1-INH-Abs exhibited strong negative correlation to the C1-inhibitor concentration and functional activity, total classical complement pathway activity, and a positive correlation to total IgM concentration. Taken together, these data indicate that IgM type C1-INH-Abs are present with highly elevated frequency in HAE patients irrespectively of the previous treatment with C1-INH concentrate. Most probable production of these autoantibodies is the consequence of the activation of complement and other plasma enzyme systems during HAE attacks. Determination of IgM C1-INH-Abs can be used as an activity marker in HAE.
C1抑制物自身抗体（C1-INH-Abs）的存在是获得性C1抑制物缺乏的一个标志。然而，关于其在遗传性血管性水肿（HAE）中的患病率仅有稀少的数据。在2001年至2004年对95例I型或II型HAE患者进行的一项前瞻性研究中，每年采集患者血清样本1至3次，并记录患者的临床状况。检测血清样本中经典途径的总活性、C1q、C3、C4和C1抑制物（C1-INH）的浓度及活性水平，以及IgG、IgA和IgM型抗C1抑制物抗体（C1-INH-Ab）的存在情况。54名年龄和性别匹配的健康人作为对照。仅在IgM型C1-INH-Abs的情况下，发现患者与对照在C1-INH-Abs滴度升高（高于对照均值2个标准差）的发生率上存在显著差异。分别在31%的患者和4%的对照中发现IgM C1-INH-Abs水平升高（>4.22AU/ml）（p<0.001）。令人惊讶的是，在41例曾接受C1-INH浓缩物治疗的HAE患者和54例未接受过C1-INH治疗的患者中，高滴度IgM C1-INH-Abs出现的频率相同。在后一组中，IgM C1-INH-Abs水平与最严重疾病（评分1）（p=0.0021）和年发作率（p=0.0173）之间存在强正相关。此外IgM C1-INH-Abs水平与C1抑制物浓度和功能活性、经典补体途径总活性呈强负相关，与总IgM浓度呈正相关。综上所述，这些数据表明，无论先前是否接受过C1-INH浓缩物治疗，HAE患者中IgM型C1-INH-Abs的出现频率都极高。这些自身抗体最可能的产生是HAE发作期间补体和其他血浆酶系统激活的结果。IgM C1-INH-Abs的测定可作为HAE的一种活性标志物。
