Up-regulation of the endoplasmic reticulum transmembrane protein UNC93B in the B cells of patients with active systemic lupus erythematosus.
OBJECTIVE
The transmembrane endoplasmic reticulum (ER) protein UNC93B plays an essential role in the normal response to signalling through intracellular Toll-like receptor (TLR)3, TLR7, TLR8 and TLR9. In the current study, we examined the level of UNC93B expression on peripheral B cells from patients with active SLE, and investigated any correlation with SLE pathogenesis.


METHODS
Peripheral blood mononuclear cells (PBMCs) and B cells from 43 active SLE patients were analysed by quantitative RT-PCR to determine the precise levels of UNC93B mRNA. We also analysed UNC93B protein expression on B cells from SLE patients using immunoblotting.


RESULTS
The expression of UNC93B mRNA on PBMCs from active SLE patients was significantly higher than that of controls (P < 0.05). The intracellular expression level of UNC93B protein on CD20(+) B cells from active SLE patients was also higher than in the controls. Moreover, the expression of UNC93B on B cells from lupus patients correlated significantly with high titres of anti-dsDNA antibody (P < 0.05).


CONCLUSIONS
Up-regulation of the ER membrane protein UNC93B on human lupus B cells suggests that TLR9 and UNC93B play a partial role in the pathogenesis of SLE by inducing defective peripheral B-cell tolerance.
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421 Japan. soubey@juntendo.ac.jp
Souichiro
S
Nakano
Shinji
S
Morimoto
Satoshi
S
Suzuki
Takashi
T
Watanabe
Hirofumi
H
Amano
Yoshinari
Y
Takasaki
D000328:Adult; D000974:Antibodies, Antinuclear / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D004721:Endoplasmic Reticulum / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000276:immunology* / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology* / Q000378:metabolism; D013223:Statistics as Topic; D051217:Toll-Like Receptor 9 / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
D000974:Antibodies, Antinuclear; D026901:Membrane Transport Proteins; D053594:Myeloid Differentiation Factor 88; D051217:Toll-Like Receptor 9; C454130:UNC93B1 protein, human