Immunological diagnostic methods in oral mucosal diseases
Immunological diagnostic methods in oral mucosal diseases
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DOI：
10.1111/bjd.17830
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发表时间：
2019-07
影响因子：
10.3
通讯作者：
T. Hashimoto;H. Nakahara
中科院分区：
文献类型：
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作者：
T. Hashimoto;H. Nakahara
本期BJD包括Sun等人的一篇广泛而实用的综述文章，其总结了用于诊断以下七种主要的口腔粘膜的自身免疫性和炎性疾病的各种免疫学方法：寻常天疱疮、副肿瘤性天疱疮、粘膜类天疱疮（MMP）、线性伊加大疱性皮肤病（LABD）、类天疱疮扁平苔藓、口腔扁平苔藓（OLP）和口腔盘状红斑狼疮（DLE）。虽然我们最近发表了一篇文章，介绍了BJD中自身免疫性大疱病（AIBD）的综合诊断方法和当前分类，但本文仅关注口腔粘膜疾病的诊断方法，包括两种非AIBD疾病，OLP和口腔DLE。本文对这些疾病的自身抗原、诊断方法和结果的解释作了广泛而准确的描述，并附有3个组织良好的表格和141篇相关参考文献。包括大量的常规和新的抗原分子检测各种免疫荧光（IF），免疫印迹和酶联免疫吸附测定（ELISA）方法。因此，这篇综述文章是非常有用的牙医和皮肤科医生从事实践的口腔粘膜疾病，也表明了合作和团队工作的必要性，牙医和皮肤科医生之间。在日常实践中，MMP是最难诊断的疾病，主要是因为其异质性的临床特征。在这种情况下，这篇文章是特别彻底的描述自身抗原和MMP的诊断方法，并应导致从业人员正确的诊断。此外，这篇文章包括独特的声明，循环抗核抗体（ANA）和抗体桥粒芯糖蛋白的相关性，这是相关的疾病严重程度。因此，这些自身抗体可能是由严重的口腔粘膜损伤以及这些自身抗原的释放和暴露于免疫系统引起的。作者还提出了通过直接IF对非日光暴露皮肤进行阳性狼疮带试验和ANA滴度增加的重要性，这可能表明DLE向系统性LE的进展。AIBD的蛋白质微阵列技术的有用性也被考虑，特别是用于检测新的自身抗原。然而，当所有的自身抗原被鉴定并且开发了这些分子的ELISA时，由于高成本，蛋白质阵列技术可能不适合用于AIBD的常规诊断。尽管Sun等人没有清楚地描述，区分具有主要伊加反应性的抗BP180型MMP和具有口腔损伤的LABD仍然是一个挑战。由于抗BP180型MMP偶尔仅显示伊加自身抗体，因此具有伊加抗基底膜带（BMZ）抗体的口腔粘膜优势病变的病例更好地诊断为IgA优势MMP，而不是LABD。另一个要点是OLP中直接IF结果的相关性，特别是补体C3颗粒沉积到BMZ。我们报告了10例严重的口腔扁平苔藓，其中直接IF清楚地显示颗粒状C3沉积到BMZ。虽然目前尚不清楚OLP中C3沉积的机制，但这种现象可能阐明颗粒状C3皮肤病的发病机制，我们提出这是一种新的疾病实体，显示颗粒状C3沉积到BMZ，而没有针对BMZ组分的自身抗体。
This issue of BJD includes an extensive and practically useful review article by Sun et al., which summarizes various immunological methods to diagnose the following seven major autoimmune and inflammatory diseases of the oral mucosa: pemphigus vulgaris, paraneoplastic pemphigus, mucous membrane pemphigoid (MMP), linear IgA bullous dermatosis (LABD), lichen planus pemphigoides, oral lichen planus (OLP) and oral discoid lupus erythematosus (DLE). Although we have recently published a paper describing comprehensive diagnostic methods and current classification in autoimmune bullous diseases (AIBDs) in the BJD, the present article focuses on the diagnostic methods only for oral mucosal diseases, including two non-AIBD diseases, OLP and oral DLE. This article describes extensively and accurately the autoantigens, diagnostic methods and interpretation of the results for these diseases, with three well-organized tables and 141 relevant references. Included are a large number of conventional and novel antigen molecules detected by various immunofluorescence (IF), immunoblotting and enzyme-linked immunosorbent assay (ELISA) methods. Thus, this review article is very useful for both dentists and dermatologists engaged in practice for oral mucosal diseases, and also suggests the necessity of collaboration and team work between dentists and dermatologists. In daily practice, MMP is the most difficult disease to diagnose mainly because of its heterogeneous clinical features. In this context, this article is particularly thorough in describing autoantigens and diagnostic methods for MMP, and should lead practitioners to the correct diagnoses. Additionally, this article includes unique statements on the relevance of circulating antinuclear antibodies (ANAs) and antibodies to desmogleins in OLP, which are correlated to disease severity. Thus, these autoantibodies may be induced by severe oral mucosal damage and the release and exposure of these autoantigens to the immune system. The authors also suggest the importance of a positive lupus band test by direct IF for non-sun-exposed skin and increase of ANA titres, which may indicate the progress of DLE to systemic LE. The usefulness of the protein microarray technique for AIBDs is also considered, particularly for the detection of novel autoantigens. However, when all the autoantigens are identified and ELISAs for these molecules are developed, the protein array technique may not be appropriate for the routine diagnosis for AIBDs, due to the high cost. Although not clearly described by Sun et al., it remains a challenge to differentiate between anti-BP180-type MMP with predominant IgA reactivity and LABD with oral lesions. Because anti-BP180-type MMP occasionally shows only IgA autoantibodies, the cases with oral mucosal-dominant lesions with IgA anti-basement membrane zone (BMZ) antibodies are better diagnosed as IgA-dominant MMP, rather than LABD. Another important point is the relevance of direct IF findings in OLP, particularly granular deposition of complement C3 to BMZ. We have reported 10 cases of severe OLP, in which direct IF clearly showed granular C3 deposition to BMZ. Although the mechanism for the C3 deposition in OLP is currently unknown, this phenomenon may clarify the pathogenesis in granular C3 dermatosis, which we proposed as a novel disease entity showing granular C3 deposition to BMZ without autoantibodies to BMZ components.