Synovial B cells of rheumatoid arthritis express ZAP-70 which increases the survival and correlates with the inflammatory and autoimmune phenotype.
B cells have acquired an important role in the pathogenesis of rheumatoid arthritis (RA) since B cell depletion allowed to rescue patients poorly responders to TNFalpha blockers. This study focused on the involvement of ZAP-70 as a bio-marker of B cells immune activation in RA. ZAP-70 expression in synovial fluid (SF) B cells obtained from RA patients was increased compared to SF B cells of osteoarthritis (OA) patients. Moreover we found that ZAP-70 positive/CD38 positive and ZAP-70 positive/CD5 positive B cells were enriched in SF. The analysis of B cell apoptosis in vitro showed that the percentage of ZAP-70 negative B cells spontaneously undergoing apoptosis was significantly higher than ZAP-70 positive B cells. The ZAP-70 positive B cell ratio (SF/peripheral blood (PB)) showed a positive correlation with SF autoantibody levels and with local levels of BAFF and IL6. ZAP-70 positive B cells seem to define a subset characterized by increased survival and high relationship with local inflammation and autoimmunity.
Tolusso
Barbara
B
Division of Rheumatology, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
De Santis
Maria
M
Bosello
Silvia
S
Gremese
Elisa
E
Gobessi
Stefania
S
Cuoghi
Ilaria
I
Totaro
Michele C
MC
Bigotti
Giulio
G
Rumi
Carlo
C
Efremov
Dimitar G
DG
Ferraccioli
Gianfranco
G
D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000276:immunology; D053264:B-Cell Activating Factor / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D001323:Autoantibodies; D053264:B-Cell Activating Factor; D015850:Interleukin-6; D012333:RNA, Messenger; C505719:TNFSF13B protein, human; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human