关键词: BALF COPD IAD RAO allergen antigen equine asthma isotype

Mesh : Animals Horses / immunology Aspergillus fumigatus / immunology Bronchoalveolar Lavage Fluid / immunology Asthma / immunology microbiology Immunoglobulin G / immunology blood Immunoglobulin A / immunology blood metabolism Horse Diseases / immunology microbiology Antigens, Fungal / immunology Male Neutrophils / immunology metabolism Female Immunoglobulin E / immunology blood Antibodies, Fungal / immunology blood

来  源:   DOI:10.3389/fimmu.2024.1406794   PDF(Pubmed)

Abstract:
UNASSIGNED: Equine asthma (EA) is a common lower airway disease in horses, but whether its pathogenesis is allergic is ambiguous. Extrinsic stimuli like hay dust induce acute exacerbation of clinical signs and sustained local neutrophilic inflammation in susceptible horses. Aspergillus fumigatus is an EA stimulus, but it is unclear if it merely acts as an IgE-provoking allergen. We aimed to comprehensively analyze immunoglobulin (Ig) isotypes in EA, elucidating their binding to different A. fumigatus antigens, and their quantities systemically in serum and locally in bronchoalveolar lavage fluid (BALF).
UNASSIGNED: Serum and BALF from healthy horses (HE, n = 18) and horses with mild-moderate asthma (MEA, n = 20) or severe asthma (SEA, n = 24) were compared. Ig isotype (IgG1, IgG3/5, IgG4/7, IgG6, IgA, and IgE) binding to nine antigens (A. fumigatus lysate, and recombinant Asp f 1, Asp f 7, Asp f 8, dipeptidyl-peptidase 5, class II aldolase/adducin domain protein, glucoamylase, beta-hexosaminidase, and peptide hydrolase) was compared by enzyme-linked immunosorbent assays. Total Ig isotype contents were determined by bead-based assays.
UNASSIGNED: MEA and SEA differed from HE but hardly from each other. Compared to HE, asthmatic horses showed increased anti-A. fumigatus binding of IgG (BALF and serum) and IgA (BALF). Serum and BALF IgE binding and total IgE contents were similar between HE and EA. Single antigens, as well as A. fumigatus lysate, yielded similar Ig binding patterns. Serum and BALF IgG1 binding to all antigens was increased in SEA and to several antigens in MEA. Serum IgG4/7 binding to two antigens was increased in SEA. BALF IgA binding to all antigens was increased in SEA and MEA. Total BALF IgG1 and IgG4/7 contents were increased in SEA, and serum IgG4/7 content was increased in MEA compared to HE. Yet, total isotype contents differentiated EA and HE less clearly than antigen-binding Ig.
UNASSIGNED: A. fumigatus immunogenicity was confirmed without identification of single dominant antigens here. A. fumigatus provoked elevated BALF IgG1 and IgA binding, and these isotypes appear relevant for neutrophilic EA, which does not support allergy. BALF Ig isotype differentiation beyond IgE is crucial for a comprehensive analysis of immune responses to fungi in EA pathogenesis.
摘要:
马哮喘(EA)是马常见的下气道疾病,但其发病机制是否为过敏性尚不明确。诸如干草粉尘之类的外在刺激会在易感马中引起临床体征的急性恶化和持续的局部嗜中性粒细胞炎症。烟曲霉是一种EA刺激物,但目前尚不清楚它是否仅仅是一种引起IgE的过敏原。我们旨在全面分析EA中的免疫球蛋白(Ig)同种型,阐明它们与不同的烟曲霉抗原的结合,以及它们在血清和支气管肺泡灌洗液(BALF)中的全身含量。
健康马的血清和BALF(HE,n=18)和轻度-中度哮喘的马(MEA,n=20)或严重哮喘(SEA,n=24)进行比较。Ig同种型(IgG1,IgG3/5,IgG4/7,IgG6,IgA,和IgE)结合9种抗原(A.烟曲霉裂解物,和重组Aspf1,Aspf7,Aspf8,二肽基肽酶5,II类醛缩酶/内加蛋白结构域蛋白,葡糖淀粉酶,β-己糖胺酶,和肽水解酶)通过酶联免疫吸附试验进行比较。通过基于珠的测定测定总Ig同种型含量。
MEA和SEA与HE不同,但彼此之间几乎没有区别。与他相比,哮喘马表现出增加的抗A。烟曲霉结合IgG(BALF和血清)和IgA(BALF)。HE和EA之间的血清和BALFIgE结合和总IgE含量相似。单一抗原,以及烟曲霉裂解物,产生类似的Ig结合模式。血清和BALFIgG1与所有抗原的结合在SEA中增加,与MEA中的几种抗原的结合增加。血清IgG4/7与两种抗原的结合在SEA中增加。在SEA和MEA中,BALFIgA与所有抗原的结合增加。SEA中BALF总IgG1和IgG4/7含量增加,与HE相比,MEA中血清IgG4/7含量增加。然而,总同种型含量与抗原结合Ig相比,EA和HE差异不明显。
A.在这里没有鉴定单个显性抗原的情况下证实了烟曲霉的免疫原性。烟曲霉引起BALFIgG1和IgA结合升高,这些同种型似乎与嗜中性EA有关,不支持过敏。BALF超越IgE的Ig同种型分化对于EA发病机理中对真菌的免疫反应的全面分析至关重要。
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