Refine
Has Fulltext
- yes (7)
Is part of the Bibliography
- yes (7)
Year of publication
- 2016 (7) (remove)
Document Type
- Journal article (7)
Language
- English (7)
Keywords
- ischemic stroke (2)
- neuroinflammation (2)
- Cerebral-ischemia (1)
- FXIIa inhibitor rHA-Infestin (1)
- Head-injury (1)
- Hemodynamic depression (1)
- IBA-1 (1)
- Intravascular coagulation (1)
- Mice (1)
- Model (1)
- Molecular-weight heparin (1)
- NEUROWIND (1)
- PET (1)
- Rats (1)
- TBI (1)
- TSPO (1)
- Thrombus formation (1)
- autoimmunity (1)
- autoradiography (1)
- blood coagulation (1)
- coagulation factor XIIa (1)
- contact activation system (1)
- dendric cells (1)
- diffuse (1)
- factor XII (1)
- focal (1)
- immune cells (1)
- immunohistochemistry (1)
- in-vivo (1)
- inflammation (1)
- lymphocytes (1)
- mechanical thrombectomy (1)
- multiple sclerosis (1)
- neuroimmunology (1)
- thrombus formation (1)
- weight drop (1)
Institute
B cell aggregates in the central nervous system (CNS) have been associated with rapid disease progression in patients with multiple sclerosis (MS). Here we demonstrate a key role of carcinoembryogenic antigen-related cell adhesion molecule1 (CEACAM1) in B cell aggregate formation in MS patients and a B cell-dependent mouse model of MS. CEACAM1 expression was increased on peripheral blood B cells and CEACAM1\(^+\) B cells were present in brain infiltrates of MS patients. Administration of the anti-CEACAM1 antibody T84.1 was efficient in blocking aggregation of B cells derived from MS patients. Along these lines, application of the monoclonal anti-CEACAM1 antibody mCC1 was able to inhibit CNS B cell aggregate formation and significantly attenuated established MS-like disease in mice in the absence of any adverse effects. CEACAM1 was co-expressed with the regulator molecule T cell immunoglobulin and mucin domain −3 (TIM-3) on B cells, a novel molecule that has recently been described to induce anergy in T cells. Interestingly, elevated coexpression on B cells coincided with an autoreactive T helper cell phenotype in MS patients. Overall, these data identify CEACAM1 as a clinically highly interesting target in MS pathogenesis and open new therapeutic avenues for the treatment of the disease.