期刊
ACS BIOMATERIALS SCIENCE & ENGINEERING
卷 8, 期 4, 页码 1486-1493出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.1c01395
关键词
rheumatoid arthritis; anti-citrullinated protein antibodies; polyisocyanopeptides; cyclic-citrullinated peptide; CD22
资金
- NWO gravitation program Institute for Chemical Immunology [NWO-024.002.009]
- ReumaNederland [17-1402, 08-1-34]
- IMI funded project RTCure [777357]
- Target to B [LSHM18055-5GF]
- NWO-ZonMW VIDI grant [09150172010067]
- ZonMW Enabling Technology Hotels grant [435002030]
- Dutch Arthritis Foundation [15-2-402, 18-1-205]
Multivalent scaffolds that carry multiple molecules with immunophenotyping or immunomodulatory properties are important for studying and modulating immune responses. In this study, polyisocyanopeptides (PICs) were used to detect autoreactive B cells and functionalized with autoantigenic peptides and a CD22 ligand to inhibit B-cell activation. These results demonstrate the potential clinical applications of PIC scaffolds in B-cell-mediated diseases.
Multivalent scaffolds that carry multiple molecules with immunophenotyping or immunomodulatory properties areinvaluable tools for studying and modulating specific functions ofhuman immune responses. So far, streptavidin-biotin-basedtetramers have been widely used for B-cell immunophenotypingpurposes. However, the utility of these tetramers is limited by theirtetravalency, the inherent immunogenicity of streptavidin (abacterial protein that can potentially be recognized by B cells),and the limited feasibility to functionalize these reagents. This has rendered tetramers suboptimal for studying rare, in particular,antigen-specific B-cell populations in the context of clinical applications. Here, we used polyisocyanopeptides (PICs), multivalentpolymeric scaffolds functionalized with around 50 peptide antigens, to detect autoreactive B cells in the peripheral blood of patientswith rheumatoid arthritis. To explore the potential immunomodulatory functionalities, we functionalized PICs with autoantigenicpeptides and a trisaccharide CD22 ligand to inhibit autoreactive B-cell activation through interference with the B-cell receptoractivation pathway, as evidenced by reduced phospho-Syk expression upon PIC binding. Given the possibilities to functionalizePICs, our data demonstrate that the modular and versatile character of PIC scaffolds makes them promising candidates for futureclinical applications in B-cell-mediated diseases
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