Identification of anti-moesin antibodies in the serums of patients with antiphospholipid syndrome.
BACKGROUND
The antiphospholipid syndrome (APS) is an acquired autoimmune disease characterized by recurrent vascular thrombosis and obstetric complications. However, the precise mechanisms by which the autoantibodies mediate disease remain to be elucidated. Moesin is an intracellular protein that links the cell membrane and cytoskeleton, mediating the formation of microtubules and cell adhesion sites as well as ruffling of the cell membrane, which is crucial for platelet activation.


METHODS
We screened the serums from patients with APS for the presence of anti-moesin antibodies (anti-moesin Abs) recognizing antigens derived from prokaryotic expression system, and investigated the effect of murine monoclonal anti-moesin Abs (anti-moesin mAbs) on platelet activation and aggregation by flow cytometry and platelet aggregation assay in vitro to study their potential pathogenic role in APS.


RESULTS
The presence of anti-amino (N)-terminal portion of moesin antibodies (anti-moesin-N Abs) was observed in 73% (73/100) patients with APS, which was significantly higher than anti-cardiolipin antibodies (aCL, 49%) and anti-β2 glycoprotein I antibodies (anti-β2GPI, 43%). Moreover, the elevated anti-moesin-N Abs levels significantly correlated with plasma levels of anti-β2GPI (rs=0.474, P<0.001) rather than aCL (P=0.203). The murine anti-moesin mAbs promote platelet activation and aggregation in vitro, which could be effectively neutralized by moesin-N.


CONCLUSIONS
In combination of the detection of aCL and anti-β2GPI, screening for the presence of anti-moesin-N Abs might has its value in facilitating the laboratory diagnosis of APS. The pathogenic role of anti-moesin-N Abs in the serums of APS patients needs to be further studied.
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China. Electronic address: ywang@sibs.ac.cn.
Xiaoyi
X
Lin
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
Qian
Q
Liang
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
Lin
L
Lin
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
Qiulan
Q
Ding
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
Xuefeng
X
Wang
Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
Ying
Y
Wang
D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000097:blood; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000276:immunology; D000918:Antibody Specificity; D016736:Antiphospholipid Syndrome / Q000097:blood* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins / Q000235:genetics / Q000276:immunology*; D015539:Platelet Activation / Q000187:drug effects / Q000276:immunology; D010974:Platelet Aggregation / Q000187:drug effects / Q000276:immunology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000276:immunology; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology; D053482:beta 2-Glycoprotein I / Q000276:immunology
D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D001323:Autoantibodies; D001324:Autoantigens; D018076:DNA, Complementary; D008840:Microfilament Proteins; D011993:Recombinant Fusion Proteins; D053482:beta 2-Glycoprotein I; C071058:moesin
Antiphospholipid Syndrome; Autoantibody; Moesin; Platelet Activation