Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy

Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy
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DOI:
10.1111/j.1528-1167.2009.02325.x
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发表时间:
2010-05-01
期刊:
影响因子:
5.6
通讯作者:
Peltola, Jukka
Peltola, Jukka
中科院分区:
医学1区
文献类型:
--
作者:
Liimatainen, Suvi;Peltola, Maria;Peltola, Jukka

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目的:癫痫患者血清中存在谷氨酸脱羧酶抗体(GADA),但GADA与癫痫发病的关系尚不明确。阳性标本经免疫组化和免疫印迹法(WB)鉴定。结果:GADA在15例患者(5.9%)和3例对照受试者(1.5%)中检出(p = 0.026)。7例患者(2.8%)GADA滴度高[>= 1,000相对单位(罗斯)/ml],其中6例患有颞叶癫痫(TLE)。所有三名GADA阳性对照受试者的滴度均较低。2/5例GADA滴度高且脑脊液(CSF)样本可用的患者鞘内合成(IS)GADA; 1例患者CSF寡克隆带。TLE患者中GADA水平升高的患病率倾向于高于额外TLE患者[比值比(OR)1.32,95%置信区间(CI)0.39-4.42; p = 0.657]。与低GADA滴度的患者(p = 0.001)和正常GADA滴度的患者(p < 0.001)相比,高GADA滴度的患者具有显著更高数量的其他自身抗体。这些患者的免疫学特征表明,他们的癫痫最可能的起源是自身免疫性。GADA阳性IS可能是持续免疫应答的标志物,可以识别可能需要进行免疫抑制治疗试验的患者。
P>Purpose:Glutamic acid decarboxylase antibodies (GADAs) have been detected in patients with epilepsy, but the clinical determinants of epilepsy associated with GADA have not been defined.Methods:We analyzed GADA with a radioimmunoassay in sera of 253 well-characterized patients with epilepsy and 200 control subjects. The positive samples were confirmed by immunohistochemistry and western blotting (WB). Sera were screened for other autoantibodies.Results:GADA were detected in 15 patients (5.9%) and in three control subjects (1.5%) (p = 0.026). Seven patients (2.8%) had high GADA titers [>= 1,000 relative units (RUs)/ml], six of whom had temporal lobe epilepsy (TLE). All three GADA-positive control subjects had low titers. Two of the five patients with high GADA titers and available cerebrospinal fluid (CSF) samples had intrathecal synthesis (IS) of GADA; one patient had CSF oligoclonal bands. The prevalence of increased levels of GADA tended to be higher in patients with TLE than in patients with extra-TLE [odds ratio (OR) 1.32, 95% confidence interval (CI) 0.39-4.42; p = 0.657]. The patients with high GADA titers had significantly higher number of other autoantibodies compared to the patients with low GADA titers (p = 0.001) and the patients with normal GADA (p < 0.001).Discussion:High GADA titers were present in a subgroup of patients; close to 90% had TLE. The immunologic profile of these patients suggests that the most probable origin of their epilepsy is autoimmune. A positive IS of GADA may be a marker of an ongoing immune response that could identify those patients in whom a trial with immunosuppressive therapy might be warranted.