title: Regression of systemic lupus erythematosus after development of an acquired toll-like receptor signaling defect and antibody deficiency.
abstract: Toll-like receptor 9 (TLR-9) and TLR-7 may have a role in the production of anti-DNA and anti-RNA autoantibodies, respectively, but murine models do not clearly demonstrate their contribution to the development of systemic lupus erythematosus (SLE). Herein we describe a patient with SLE who had long-lasting remission of her autoimmune disease after development of an antibody deficiency resembling common variable immunodeficiency (CVID). After CVID had developed, anti-double-stranded DNA antibodies disappeared, although antinuclear antibodies remained positive for >10 years. In vitro studies revealed that the patient's B cells proliferated poorly and failed to differentiate into plasmablasts after stimulation of either TLR-9 or TLR-7, providing evidence for an acquired defect of the signaling pathway downstream of these TLRs. These observations suggest, although indirectly, that signaling through TLR-9 and TLR-7 is important in the pathogenesis of human SLE, and indicate that investigation of potential treatment strategies with TLR antagonists is warranted.
authors.affiliation: Department of Clinical Immunology, Sapienza University, Viale dell'Università 37, Rome, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Visentini
authors.forename: Valentina
authors.initials: V
authors.lastname: Conti
authors.forename: Maria
authors.initials: M
authors.lastname: Cagliuso
authors.forename: Francesca
authors.initials: F
authors.lastname: Tinti
authors.forename: Giulia
authors.initials: G
authors.lastname: Siciliano
authors.forename: Amelia C
authors.initials: AC
authors.lastname: Trombetta
authors.forename: Anna Paola
authors.initials: AP
authors.lastname: Mitterhofer
authors.forename: Massimo
authors.initials: M
authors.lastname: Fiorilli
authors.forename: Isabella
authors.initials: I
authors.lastname: Quinti
mesh_terms: D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000378:metabolism; D017074:Common Variable Immunodeficiency / Q000276:immunology / Q000503:physiopathology*; D004247:DNA / Q000276:immunology; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis* / Q000276:immunology / Q000503:physiopathology*; D011379:Prognosis; D012074:Remission Induction; D015398:Signal Transduction / Q000502:physiology; D051199:Toll-Like Receptor 7 / Q000502:physiology*; D051217:Toll-Like Receptor 9 / Q000502:physiology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D004247:DNA