The Second Study of Clinical and Immunological Findings in Anti-laminin 332-Type Mucous Membrane Pemphigoid Examined at Kurume University-Diagnosis Criteria Suggested by Summary of 133 Cases.
The Second Study of Clinical and Immunological Findings in Anti-laminin 332-Type Mucous Membrane Pemphigoid Examined at Kurume University-Diagnosis Criteria Suggested by Summary of 133 Cases.
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DOI：
10.3389/fimmu.2021.771766
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发表时间：
2021
影响因子：
7.3
通讯作者：
Hashimoto T
中科院分区：
文献类型：
--
作者：
Qian H;Natsuaki Y;Koga H;Kawakami T;Tateishi C;Tsuruta D;Ishii N;Li X;Hashimoto T
最近，我们发表了一篇文章回顾性总结了在库尔斯克大学检查的55例抗层粘连蛋白332（LM 332）型粘膜类天疱疮（MMP）病例的结果，这些病例是通过严格的入选标准诊断的，包括直接免疫荧光阳性反应和不存在非LM 332自身抗原的抗体。然而，使用1 M-NaCl分裂正常人皮肤（ssIIF）的间接免疫荧光对于诊断抗LM 332型MMP也是有价值的。在第二项研究中，我们选择了133例抗LM 332型MMP病例，这些病例通过我们不同的入选标准进行诊断：（i）通过直接免疫荧光检测免疫球蛋白G（IgG）沉积到基底膜区（BMZ），或通过ssIIF检测IgG与裂开皮肤的真皮侧的反应性，（ii）通过纯化的人LM 332的免疫印迹检测LM 332的三个亚基中的至少一个为阳性，和（iii）粘膜损伤的存在。总结临床、组织病理学和免疫学结果并进行统计学分析。尽管这些病例包括55例既往病例，但对更大规模的患者进行了更详细的研究，以进一步表征。临床上，在133例患者中，89%和43%的患者分别有口腔和眼粘膜病变，71%有皮肤病变，17%有相关恶性肿瘤。组织病理学上93%的患者出现表皮下水疱。ssIIF和直接免疫荧光的灵敏度相似，但显著高于使用非分裂人皮肤的间接免疫荧光（均p < 0.001）。在纯化的LM 332的免疫印迹中，患者IgG抗体最常与LMγ2亚基（58%）反应，其次是LMα3（49%）和LMβ3（36%）。34%的患者识别出其他非LM 332自身抗原。统计学分析表明，针对非LM 332自身抗原的自身抗体可能刺激抗LM γ2抗体的产生。本回顾性研究进一步详细描述了133例抗LM 332型MMP的临床和免疫学特征，其中无阳性直接免疫荧光反应的新诊断标准有助于诊断。抗LM γ2抗体阳性率高，提示该亚基的致病作用更显著。在三分之一的患者中检测到的针对非LM 332自身抗原的其他自身抗体可能导致抗LM 332型MMP的复杂性，包括抗LM γ2抗体的诱导。
Recently, we published an article retrospectively summarizing the results in 55 anti-laminin 332 (LM332)-type mucous membrane pemphigoid (MMP) cases examined at Kurume University, which were diagnosed by strict inclusion criteria, including positive reactivity in direct immunofluorescence and absence of antibodies to non-LM332 autoantigens. However, indirect immunofluorescence using 1M-NaCl-split normal human skin (ssIIF) is also valuable for diagnosis of anti-LM332-type MMP. In this second study, we selected 133 anti-LM332-type MMP cases, which were diagnosed by our different inclusion criteria: (i) immunoglobulin G (IgG) deposition to basement membrane zone (BMZ) by direct immunofluorescence or IgG reactivity with dermal side of split skin by ssIIF, (ii) positivity for at least one of the three subunits of LM332 by immunoblotting of purified human LM332, and (iii) the presence of mucosal lesions. Clinical, histopathological, and immunological findings were summarized and analyzed statistically. Although these cases included the 55 previous cases, the more detailed study for larger scale of patients was conducted for further characterization. Clinically, among the 133 patients, 89% and 43% patients had oral and ocular mucosal lesions, respectively, 71% had cutaneous lesions, and 17% had associated malignancies. Histopathologically, 93% patients showed subepidermal blisters. The sensitivities of ssIIF and direct immunofluorescence are similar but are significantly higher than indirect immunofluorescence using non-split human skin (both p < 0.001). In immunoblotting of purified LM332, patient IgG antibodies most frequently reacted with LMγ2 subunit (58%), followed by LMα3 (49%) and LMβ3 (36%). Thirty-four percent patients recognized additional non-LM332 autoantigens. Statistical analysis revealed that autoantibodies against non-LM332 autoantigens might stimulate the production of anti-LMγ2 antibodies. This retrospective study further characterized in more detail the clinical and immunological features of 133 cases of anti-LM332-type MMP, in which the new diagnostic criteria without positive direct immunofluorescence reactivity were useful for the diagnosis. Higher frequency with anti-LMγ2 antibodies suggested more significant pathogenic role of this subunit. Additional autoantibodies to non-LM332 autoantigens detected in one-third of the patients may contribute to complexity in anti-LM332-type MMP, including the induction of anti-LMγ2 antibodies.