B-cell subsets up-regulate α4 integrin and accumulate in the cerebrospinal fluid in clinically isolated syndrome suggestive of multiple sclerosis onset.
During the pathogenesis of multiple sclerosis (MS), activated B-cells cross the inflamed endothelium of the central nervous system (CNS) to exert their effector functions, probably associated with the action of several adhesion molecules. B-cell mobilization towards the CNS already occurs after the first demyelinating events suggestive of MS, known as clinically isolated syndrome (CIS). However, little is known about the role of these adhesion molecules at this early disease stage. We, therefore, evaluated the relationship between the expression of α4 integrin by peripheral B-cell subsets and disease activity. We found that α4 integrin was up-regulated in all B-cell subsets from patients with CIS and that its expression was correlated with the number of gadolinium-enhanced lesions. A comparison of B-cell subsets distribution in the CSF of patients with CIS, of patients with other inflammatory neurological diseases (OIND) and of patients with non-inflammatory neurological diseases (NIND) showed that the percentages of CSF CD19(+) B-cells were significantly higher in the CIS and OIND group. In addition, CIS and OIND CSF were enriched in switched and MZ-like memory B-cells, although all B-cell subsets were present. These results suggest that up-regulation of α4 integrin may enhance B-cell accumulation within the CSF at the time of CIS.
Université de Lille Nord de France, France.
Catalina
C
Lee-Chang
Hélène
H
Zéphir
Isabelle
I
Top
Sylvain
S
Dubucquoi
Jacques
J
Trauet
Lionel
L
Prin
Patrick
P
Vermersch
D000328:Adult; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D003711:Demyelinating Diseases / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D039441:Integrin alpha4 / Q000096:biosynthesis* / Q000134:cerebrospinal fluid; D008297:Male; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation
D039441:Integrin alpha4