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Role of β2-glycoprotein i in the pathogenesis of the antiphospholipid syndrome

Rheumatology & Autoimmunity 2023年第3期3卷 131-139页

作者： Jing Li Xiangrui Zhu Juan Feng Department of Endocrinology Beijing ChaoYang HospitalCapital Medical UniversityBeijingChina Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking UniversityBeijingChina Department of integration of Chinese and Western Medicine School of Basic Medical SciencesPeking UniversityBeijingChina

Antiphospholipid syndrome(APS)is typically characterized by increased levels of three classes of antiphospholipid antibodies,namely lupus anticoagulant,anti-β2-glycoprotein i(anti-β2GPi),and anticardiolipin antibodies.β2-glycoprotein(β2GPi)is a phospholipid-binding protein composed of five domains(Di-V)and a major antigen in APS.β2GPi is expressed on the surfaces of several cell types,including endothelial cells,monocytes,trophoblast cells,and platelets.its binding to the anti-β2GPi antibody triggers downstream signaling events and ultimately exerts a variety of cellular effects.β2GPi modulates hemostasis and the complement system,as well as playing an important role in APS-associated vascular injury.Therefore,studying β2GPi will help elucidate the pathogenesis of APS and improve the treatment of patients with this condition.This review will mainly focus on the structure and function of β2GPi,as well as its implication in the pathogenesis of APS.

关键词： antiphospholipid syndrome coagulation complement inflammation β2-glycoprotein i

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T cells from induced and spontaneous models of SLE recognize a common T cell epitope on β2-glycoprotein Ⅰ

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Cellular & Molecular immunology 2019年第8期16卷 685-693页

作者： David Salem Rebecca Subang Masataka Kuwana Jerrold S.Levine Joyce Rauch Division of Rheumatology Department of MedicineResearch Institute of the McGill University Health CentreMontrealQCCanada Department of Allergy and Rheumatology Nippon Medical SchoolGraduate School of MedicineTokyoJapan Section of Nephrology Department of MedicineUniversity of Illinois at ChicagoChicagoILUSA Section of Nephrology Department of MedicineJesse Brown Veterans Affairs Medical CenterChicago IL USA

Systemic lupus erythematosus is a prototypic model for B-cell epitope spread in autoimmunity.Autoantibodies to numerous molecularly distinct self-antigens emerge in a sequential manner over several years,leading to disease manifestations.Among the earliest autoantibodies to appear are those targeting phospholipid-binding proteins,particularlyβ2-glycoprotein Ⅰ.Notably,mice immunized with β2-glycoprotein Ⅰ and lipopolysaccharide develop a strong T cell response to β2-glycoprotein Ⅰ that is associated with autoantibody production and renal disease,similar to that seen in human SLE.Here we hypothesized that mice with murine systemic lupus erythematosus,whether induced or spontaneous,should have T cells that recognizeβ2-glycoprotein i.We evaluated the response of splenic T cells from mice with induced(C57BL/6 and C3H/HeN)and spontaneous(MRL/lpr)systemic lupus erythematosus to peptides spanning the entire sequence of humanβ2GPi.We found that mice with induced and spontaneous systemic lupus erythematosus recognize a common T cell epitope(peptide 31;LYRDTAVFECLPQHAMFG)in domain Ⅲ ofβ2-glycoprotein i.β2GPi-reactive CD4^(+)T cells from the two models differed primarily in cytokine production:T cells from mice with induced SLE expressed iFN-γ,while T cells from MRL/lpr mice expressed both iL-17 and iFN-γ,indicating that iL-17-expressing T cells are not necessary for generating aβ2GPi-reactive T cell response.These data suggest that the generation of aβ2-glycoprotein ireactive T cell response is shared by both induced and spontaneous models of systemic lupus erythematosus and that this T cell response may mediate epitope spread to autoantibodies in both models.

关键词： β2-glycoprotein i T cells systemic lupus erythematosus autoantibodies MHC class ii haplotypes

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Proteomic analysis of human serum from diabetic retinopathy

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international Journal of Ophthalmology(English edition) 2011年第6期4卷 616-622页

作者： Yin-Ping Liu, Xiao-He Lu Department of Ophthalmology Zhujiang Hospital Southern Medical University Guangzhou 510282 Guangdong Province China Department of Pathophysiology Southern Medical University Guangzhou 510515 Guangdong Province China Department of Ophthalmology Yijishan Hospital Wannan Medical College Wuhu 241001 Anhui Province China

AiM: To establish and compare serum proteomic of diabetic retinopathy (DR) patients in various phases and discuss pathogenesis of DR so as to find out possible serum specific molecular markers for early diagnosis of DR. METHODS: Thirty-two subjects were divided into four groups: one group of eight type 2 diabetes mellitus (T2DM) patients without apparent DR (No-DR, NDR), one group of eight T2DM patients with non-proliferative diabetic retinopathy (NPDR), one group of eight T2DM patients with proliferative diabetic retinopathy(PDR) and one group of eight healthy volunteer participants. Two dimensional fluorescence difference gel electrophoresis (2D-DiGE) was applied to establish differential protein expression profiles in four groups. Matrix-assisted laser desorption/ionization time of flight tandem mass spectrometry (MALDi-TOF-TOF MS) was applied to identify mass spectrometry of differential proteins and analyze follow-up bioinformatics. RESULTS: 2D-DiGE maps of serum protein were satisfactory obtained from NDR, NPDR, PDR and normal control groups. Twenty-six different proteins spots were screened(the volume ratio was > 1.5 based on DeCyder software analysis). Twenty-four of them were verified and two of them were not. Fifteen proteins were verified. Most of them were high-abundant proteins in serum. The four relatively low-abundant ones were beta 2-glycoprotein i (beta (2)-GPi), alpha2-HS-glycoprotein (AHSG), alpha1-acid glycoprotein (alpha(1)-AGP) and apolipoprotein A-1 (apo A-1). beta (2)-GPi expression was gradually increased in the development of DR but unrelated to the severity of DR. The volume ratio of beta (2)-GPi is 1.54, 2.43, and 2.84 in NDR, NPDR and PDR group respectively compared with normal control group. CONCLUSiON: Serum proteomic analysis of 2D-DiGE combined with MALDi-TOF-TOF MS is feasible to be applied in the study of DR. 13 2-GPi probably takes part in the process of DR occurrence and development and it could be a candidate biomarker on DR diagnosis in early phase.

关键词： diabetic retinopathy difference gel electrophoresis β2-glycoprotein i proteomics serum type 2 diabetes

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