Sato M N, Carvalho A F, Silva A O, MacIel M, Fusaro A E, Duarte A J
Laboratório de Imunogenética e Transplante Experimental LIM-56, Faculdade de Medicina da USP (FMUSP), São Paulo, Brasil.
Immunology. 1998 Oct;95(2):193-9. doi: 10.1046/j.1365-2567.1998.00594.x.
We investigated the effect on specific antibody response of naive and sensitized mice orally administrated with low (0.25 mg) or high (10.0 mg) doses of Dermatophagoides pteronyssinus (Dp) extract. We also examined the effect of oral administration of Dp on the production of autoantibodies to immunoglobulin G (IgG) and immunoglobulin E (IgE). Naive and sensitized mice both showed a marked down-regulation of IgE antibody production, regardless of the dose of Dp. We also detected an inhibitory effect of the total IgE levels and the allergen-specific IgG1, IgG2a and IgG2b antibody response in sensitized mice given the low dose of Dp. In contrast, high doses of Dp stimulated IgG1 antibody production in both naive and sensitized animals. In addition, the oral tolerance induction protocol stimulated anti-F(ab')2gamma and anti-Fcgamma autoantibody production. Evaluation of IgG anti-IgE autoantibodies by a direct enzyme immunoassay (EIA) revealed the presence of these autoantibodies, predominantly of the IgG1 isotype, specifically in those animals fed with the high dose. In contrast, IgG-IgE complexes, determined by EIA using immobilized anti-IgE antibodies, were detected mainly in sera of control animals. The autoantibody anti-IgE specificity was tested against IgE-TNP and IgE-DANSYL murine proteins and revealed different inhibition profiles, suggesting the action of heterogeneous subpopulations of autoantibodies. Taken together, our results show that the oral tolerance protocol with Dp was able to modulate the production of allergen-specific IgE antibodies in both naive and sensitized animals. In addition, we suggest that anti-IgE autoantibodies participate in the modulation of allergic response triggered by oral tolerance protocols.
我们研究了低剂量(0.25毫克)或高剂量(10.0毫克)的屋尘螨提取物经口给予未致敏和致敏小鼠后对特异性抗体反应的影响。我们还检测了经口给予屋尘螨提取物对免疫球蛋白G(IgG)和免疫球蛋白E(IgE)自身抗体产生的影响。无论屋尘螨提取物的剂量如何,未致敏和致敏小鼠均显示出IgE抗体产生的显著下调。我们还检测到低剂量屋尘螨提取物对致敏小鼠的总IgE水平以及变应原特异性IgG1、IgG2a和IgG2b抗体反应具有抑制作用。相比之下,高剂量的屋尘螨提取物刺激了未致敏和致敏动物体内IgG1抗体的产生。此外,口服耐受诱导方案刺激了抗F(ab')2γ和抗Fcγ自身抗体的产生。通过直接酶免疫测定法(EIA)对IgG抗IgE自身抗体进行评估,结果显示这些自身抗体存在,主要为IgG1同种型,尤其在给予高剂量提取物的动物中。相比之下,使用固定化抗IgE抗体通过EIA测定的IgG-IgE复合物主要在对照动物的血清中检测到。针对IgE-TNP和IgE-DANSYL鼠蛋白测试了抗IgE自身抗体的特异性,结果显示出不同的抑制谱,表明存在异质性自身抗体亚群。综上所述,我们的结果表明,屋尘螨提取物的口服耐受方案能够调节未致敏和致敏动物体内变应原特异性IgE抗体的产生。此外,我们认为抗IgE自身抗体参与了口服耐受方案引发的过敏反应的调节。