THE MUCOSAL AND SERUM IGA SYSTEMS IN AIDS

尽管在理解这些问题上取得了令人印象深刻的进展 艾滋病病原体的生物学及其基础 致病性、新发病例持续增加 在世界范围内以对数速度增长，目前没有可用的手段 不是预防就是治愈。艾滋病是由许多人指定的 免疫异常，其中一些还知之甚少。其中之一 相对无特征性的免疫功能紊乱 在艾滋病是一种明显的免疫球蛋白A调节功能障碍。这是 以相反影响的血清和分泌型IgA水平为特征 (通常在其他水平没有变化的情况下 免疫球蛋白同工型)，以及升高的IgA水平- 含有免疫复合体和IgA类风湿因子(RF)。 了解这些通常是IgA特异性的免疫病理 因为IgA免疫系统在一种疾病中是必不可少的 通常是粘膜获得性的，并与多发性 粘膜表面继发感染。因此，我们将使用 已知的血清学和结构差异 分泌型IgA阐明产生的IgA的来源和功能 通过系统和粘膜的免疫球蛋白A系统在艾滋病。在手机上 水平，我们将研究免疫球蛋白亚型，包括 外周血产生的免疫球蛋白A亚类和分子形式 乙状结肠的淋巴细胞、骨髓和淋巴样细胞 艾滋病患者；我们将对艾滋病毒特异性进行类似的分析 由相同的细胞群产生的抗体。由于血清免疫球蛋白A 通常主要在骨髓中产生，我们将检查 艾滋病患者骨髓细胞对IgA合成的调节 病人。我们将研究IgA抗体的功能作用， 特别是关于：抗体介导的艾滋病毒增强 传染性；在调解或抑制ADCC和HIV方面的作用 中和；和鉴定IgA自身抗体。其他 研究的目的是确定IgA RF的细胞起源， 使用上面定义的相同细胞群。我们还将 血清和分泌物(唾液)IgA和IgA的特征 针对IgA亚类和HIV的HIV特异性抗体 分子形式。最后，我们将进一步分析IgA- 在艾滋病患者的血清中含有免疫复合体 将这些复合体的组成和水平与 临床状态。这些研究将回答以下基本问题 通常被认为是免疫球蛋白同型的免疫球蛋白IgA的作用 无法通过经典机制保护宿主，在 艾滋病的发病机制是一种值得注意的疾病 免疫球蛋白A调节异常。

Although impressive progress has been made toward understanding the biology of the etiologic agent of AIDs as well as the basis of its pathogenicity, new cases of the disease continue to increase worldwide at logarithmic rates, with no currently available means of either prevention or cure. AIDS is earmarked by a multitude of immune abnormalities, some of which are poorly understood. One of the relatively uncharacteracterized disorders of immune function in AIDS is an apparent dysfunction of IgA regulation. This is typified by inversely affected levels of serum and secretory IgA (often in the absence of alterations in the levels of other immunoglobulin isotypes), as well as elevated levels of IgA- containing immune complexes and IgA rheumatoid factor (RF). Understanding these often IgA-specific immunopathologies as well as the IgA immune system in general is imperative in a disease that is so often mucosally acquired as well as associated with multiple secondary infections at mucosal surfaces. Therefore, we will use the known serological and structural differences of serum and secretory IgA to elucidate the origin and function of IgA produced by the systemic and mucosal IgA systems in AIDS. At the cellular level we will study the immunoglobulin isotypes, including subclasses and molecular form of IgA, produced by peripheral blood lymphocytes, bone marrow, and lymphoid cells of sigmoid colon of AIDS patients; we will perform similar analyses on HIV-specific antibodies produced by the same cell populations. Since serum IgA is normally produced primarily in the bone marrow, we will examine the regulation of IgA synthesis by bone marrow cells of AIDS patients. We will examine the functional role of IgA antibodies, specifically with regard to: antibody-mediated enhancement of HIV infectivity; role in mediation or inhibition of ADCC and HIV neutralization; and identification of IgA autoantibodies. Other Studies will aim at identifying the cellular origins of IgA RF, using the same cell populations defined above. We will also characterize both serum and secretory (salivary) IgA and IgA antibodies specific for HIV with respect to IgA subclass and molecular form. Finally, we will further analyze the IgA- containing immune complexes in the sera of AIDS patients and correlate the composition and levels of these complexes with clinical status. These studies will answer basic questions as to the role of IgA, an immunoglobulin isotype generally considered incapable of protecting the host by classical mechanisms, in the pathogenesis of AIDS, a disease characterized by notable aberrations in IgA regulation.