Autoantibodies are important biomarkers that can be used to aid in the diagnosis of different autoimmune diseases. At Creative Biolabs, we have the expertise in the development, optimization, validation, and execution of various immunoassay formats targeting a wide range of biomarkers. Especially, we offer in vitro diagnostic (IVD) immunoassay development services to detect autoantibody biomarkers of mucous membrane pemphigoid (MMP).
MMP autoantibodies can be produced against a variety of autoantigens, including the bullous pemphigoid antigen 1 (BPAg1, a 230 kDa protein, BP230), the bullous pemphigoid antigen 2 (BPAg2, a 180 kDa protein, BP180), integrin subunits α6/β4, laminin-332 (also called epiligrin and laminin-5), laminin-6, and collagen type I identified by using immunoblotting and immunoprecipitation techniques. BP230 is an intracellular protein, whereas BP180 and α6/β4 integrins are transmembrane proteins. The most frequently targeted autoantigen in MMP is BP180.
Basic Structure and Epitope Profiles of BP180
The BP180 has a 16th non-collagenous (NC16A) domain, which is a type II transmembrane protein with a cytosolic NH2 terminal and an extracellular COOH domain. The N-terminal domain, transmembranous stretch, and extracellular C-terminus have 466, 23, and 1,008 amino acids in length, respectively. The ectodomain contains 15 collagenous subdomains (COL1-COL15) interspersed by 16 non-collagenous sequences (NC1-NC16). The NC16A domain, a juxtamembrane linker region, appears to be biologically important, as it serves as the nucleus for the formation of a collagen-like triple helix. BP180 contains multiple binding sites for hemidesmosome proteins, including the extracellular domains of integrin α6 and laminin-332.
The extracellular NC16A domain has seven antigenic sites, including NC16A1, NC16A1-3, NC16A1-5, NC16A2, NC16A2.5, NC16A3, and NC16A3-4. Among these sites, NC16A2 and NC16A2.5 are the major antigenic sites, which can be targeted by all IgG and IgE antibodies.
Fig.1 The target sites of the BP180 molecule. BP180 is a multi-epitope protein with three major domains-the intracellular domain (ICD), the NC16A domain and the ectodomain outside the NC16A domain.1
Autoantibody Targeting NC16A of BP180
Previous studies pointed out that the NC16A might be the major pathogenic epitope in MMP. There are three possible mechanisms associated with the autoantibodies with ICD or ectodomain:
Fig.2 The potential pathogenesis of the anti-BP180 autoantibodies targeting the ICD or the ectodomain outside theNC16A. (Liu, 2019)
IVD Immunoassay Development Services Provided by Creative Biolabs
Detection of autoantibodies targeting BP180 with immunoassay technology is one of the approaches to aid in the diagnosis of MMP. These immunoassays are based on the specific recognition between the autoantibodies and the pre-coated antigen. With extensive experience in the IVD field, Creative Biolabs offers custom IVD immunoassay development services for BP180 autoantibody measurement. We are equipped with expertise in the production and purification of autoimmune antigens from native sources, as well as in the design, development, validation, and optimization of various immunoassay formats. Our professional project management team assists you throughout the entire course of a project. Creative Biolabs offers comprehensive contract development services including:
Please feel free to contact us for more information and discuss your project needs.
Reference
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