Department of Internal Medicine, University of Perugia, Perugia, Italy.
Eur J Endocrinol. 2010 Aug;163(2):309-17. doi: 10.1530/EJE-10-0257. Epub 2010 May 24.
Steroid-producing cell autoantibodies (SCAs) directed against 21-hydroxylase autoantibodies (21OHAbs), 17alpha-hydroxylase autoantibodies (17OHAb), and cholesterol side-chain cleavage enzyme (side-chain cleavage autoantibodies, P450sccAb) characterize autoimmune primary ovarian insufficiency (SCA-POI). The aim of the study was to analyze IgG subclass specificity of autoantibodies related to adrenal and ovarian autoimmunity.
We studied 29 women with SCA-POI, 30 women with autoimmune Addison's disease (AAD) without POI, and 14 patients with autoimmune polyendocrine syndrome type 1 (APS1). 21OHAb isotypes were also analyzed in 14 subjects with preclinical AAD. Samples from 30 healthy women served as control group to determine the upper level of normality in the isotype assays.
Immunoradiometric assays with IgG subclass-specific secondary antibodies.
In 21OHAb-positive sera, IgG1 isotype was detected in 90% SCA-POI and non-POI AAD sera and 67% APS1 patients. IgG1 isotype was found in 69% 17OHAb-positive SCA-POI and 100% 17OHAb-positive APS1 sera, and in 60% P450sccAb-positive SCA-POI and 80% P450sccAb-positive APS1 sera. For 21OHAb, IgG4 isotype was detected in 17% SCA-POI, 7% non-POI AAD, and 8% APS1 sera. None of the 17OHAb-positive sera was positive for IgG4. In P450sccAb-positive sera, 15% POI and 20% APS1 sera were positive for IgG4. Two 21OHAb-positive SCA-POI (7%), one 21OHAb-positive AAD (3%), three P450sccAb-positive SCA-POI (15%), and two P450sccAb-positive APS1 (20%) sera were positive for IgG4, in the absence of IgG1. All preclinical AAD sera resulted as positive for IgG1-21OHAb, but not for IgG4-21OHAb.
The autoantibody responses in POI and AAD are IgG1 dominated, which suggests a predominant Th1 response. Selective IgG4 isotype specificity identified a small subset of patients with Th2-oriented response.
针对 21-羟化酶自身抗体(21OHAbs)、17α-羟化酶自身抗体(17OHAb)和胆固醇侧链裂解酶(侧链裂解自身抗体,P450sccAb)的类固醇产生细胞自身抗体(SCAs)可用于表征自身免疫性原发性卵巢功能不全(SCA-POI)。本研究的目的是分析与肾上腺和卵巢自身免疫相关的自身抗体的 IgG 亚类特异性。
我们研究了 29 名 SCA-POI 女性、30 名无 POI 自身免疫性 Addi son 病(AAD)女性和 14 名自身免疫性多内分泌综合征 1 型(APS1)患者。还对 14 名临床前 AAD 患者进行了 21OHAb 同种型分析。30 名健康女性的样本作为对照组,以确定同种型测定的正常上限。
免疫放射测定法,使用 IgG 亚类特异性二级抗体。
在 21OHAb 阳性血清中,90%的 SCA-POI 和非 POI AAD 血清以及 67%的 APS1 患者中检测到 IgG1 同种型。在 69%的 17OHAb 阳性 SCA-POI 和 100%的 17OHAb 阳性 APS1 血清以及 60%的 P450sccAb 阳性 SCA-POI 和 80%的 P450sccAb 阳性 APS1 血清中发现 IgG1 同种型。对于 21OHAb,在 17%的 SCA-POI、7%的非 POI AAD 和 8%的 APS1 血清中检测到 IgG4 同种型。没有一个 17OHAb 阳性血清为 IgG4 阳性。在 P450sccAb 阳性血清中,15%的 POI 和 20%的 APS1 血清为 IgG4 阳性。两名 21OHAb 阳性 SCA-POI(7%)、一名 21OHAb 阳性 AAD(3%)、三名 P450sccAb 阳性 SCA-POI(15%)和两名 P450sccAb 阳性 APS1(20%)血清在没有 IgG1 的情况下为 IgG4 阳性。所有临床前 AAD 血清均为 IgG1-21OHAb 阳性,但 IgG4-21OHAb 阴性。
POI 和 AAD 中的自身抗体反应以 IgG1 为主,这表明存在以 Th1 反应为主。选择性 IgG4 同种型特异性确定了一小部分以 Th2 为导向的反应患者。