Altered BANK1 expression is not associated with humoral autoimmunity in chronic joint inflammation.
OBJECTIVE
The presence of disease-specific autoantibodies in RA but not spondyloarthritis (SpA) suggests that B-cell tolerance is preserved in the latter condition despite chronic joint inflammation. Which factors control B-cell tolerance vs autoimmunity in chronic arthritis remains incompletely understood. As single nucleotide polymorphisms in the B-cell scaffold protein with ankyrin repeats (BANK1) gene have recently been associated with various autoantibody-positive autoimmune diseases including RA, we explored whether altered expression of BANK1 was associated with humoral autoimmunity in arthritis.


METHODS
Peripheral B-cell subsets and inflamed synovial tissue were obtained from active SpA and RA. Quantitative PCR was used to assess the expression of full-length BANK1 and delta2 BANK1, a splice variant lacking exon 2 that counteracts BANK1 function. B-cell subsets, autoantibody titres and clinical disease were monitored upon CIA induction in Bank1 knockout (KO) mice.


RESULTS
Whereas full-length BANK1 was not differentially expressed, the BANK1 delta2 splicing variant was decreased in naïve peripheral B cells as well as in synovial tissue of SpA compared with RA. However, no differences were observed in seropositive vs seronegative RA. Performing functional analysis in mice, we found no differences in B-cell subsets and anti-collagen antibodies upon CIA induction between Bank1 KO mice and littermate controls. Accordingly, the incidence and severity of clinical disease were not altered in Bank1 KO mice.


CONCLUSIONS
This study did not reveal a major role for BANK1 in humoral autoimmunity in chronic arthritis. The decreased levels of BANK1 delta2 in SpA, however, warrant more detailed analysis of the functional consequences of an altered BANK1/BANK1 delta2 balance.
Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
Tineke
T
Cantaert
Natalyia G
NG
Yeremenko
Christine A
CA
Teitsma
Leonie M
LM
van Duivenvoorde
Jackeline E
JE
Paramarta
Paul-Peter
PP
Tak
Dominique L
DL
Baeten
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity / Q000235:genetics*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D016022:Case-Control Studies; D015331:Cohort Studies; D017931:DNA Primers / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D056724:Immunity, Humoral / Q000235:genetics*; D016130:Immunophenotyping; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D025241:Spondylarthritis / Q000276:immunology*; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D001323:Autoantibodies; C447641:BANK1 protein, human; D017931:DNA Primers; D008565:Membrane Proteins; D012333:RNA, Messenger