title: Anti-SSB/La is one of the antineutrophil autoantibodies responsible for neutropenia and functional impairment of polymorphonuclear neutrophils in patients with systemic lupus erythematosus.
abstract: 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.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: S-C
authors.initials: SC
authors.lastname: Hsieh
authors.forename: H-S
authors.initials: HS
authors.lastname: Yu
authors.forename: W-W
authors.initials: WW
authors.lastname: Lin
authors.forename: K-H
authors.initials: KH
authors.lastname: Sun
authors.forename: C-Y
authors.initials: CY
authors.lastname: Tsai
authors.forename: D-F
authors.initials: DF
authors.lastname: Huang
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Tsai
authors.forename: C-L
authors.initials: CL
authors.lastname: Yu
mesh_terms: 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
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D018076:DNA, Complementary; D016209:Interleukin-8; D012261:Ribonucleoproteins; D000097585:SS-B Antigen