Anti-SSB/La is one of the antineutrophil autoantibodies responsible for neutropenia and functional impairment of polymorphonuclear neutrophils in patients with systemic lupus erythematosus.
Decreased number and impaired functions of polymorphonuclear neutrophils (PMN) due to the presence of anti-PMN autoantibodies in the serum render patients with systemic lupus erythematosus (SLE) susceptible to bacterial infections. However, the cognate antigens and pathological mechanisms of anti-PMN autoantibodies in SLE are rarely reported in the literature. In this study, we found approximately 20% of SLE sera contained anti-PMN autoantibodies detected by human PMN-coated cellular ELISA. A membrane protein with molecular weight of 50 kDa was identified as the cognate antigen of anti-PMN in Western blot after membrane-biotinylation and streptavidin column elution. The 50 kDa molecule was proved to be SSB/La after immunoscreening, molecular cloning and nucleotide sequencing of the gene from the human leucocyte cDNA library. Human anti-SSB/La autoantibodies purified from active SLE sera passing through the recombinant SSB/La conjugated Sepharose 4B affinity column could bind and penetrate into normal human PMN. Functional analysis revealed that the anti-SSB/La autoantibodies exerted a number of potent effects on human PMN, including suppressed phagocytosis, accelerated apoptosis and enhanced IL-8 production. These in vitro results suggest that anti-SSB/La is one of the anti-PMN autoantibodies capable of penetrating into PMN and responsible for neutropenia and functional impairment of PMN in patients with SLE.
Hsieh
S-C
SC
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Yu
H-S
HS
Lin
W-W
WW
Sun
K-H
KH
Tsai
C-Y
CY
Huang
D-F
DF
Tsai
Y-Y
YY
Yu
C-L
CL
D017209:Apoptosis / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D002846:Chromatography, Affinity; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D019169:Jurkat Cells; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008969:Molecular Sequence Data; D009503:Neutropenia / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D012261:Ribonucleoproteins / Q000235:genetics / Q000276:immunology*; D000097585:SS-B Antigen
D001323:Autoantibodies; D001324:Autoantigens; D018076:DNA, Complementary; D016209:Interleukin-8; D012261:Ribonucleoproteins; D000097585:SS-B Antigen