Regression of systemic lupus erythematosus after development of an acquired toll-like receptor signaling defect and antibody deficiency.
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.
Visentini
Marcella
M
Department of Clinical Immunology, Sapienza University, Viale dell'Università 37, Rome, Italy.
Conti
Valentina
V
Cagliuso
Maria
M
Tinti
Francesca
F
Siciliano
Giulia
G
Trombetta
Amelia C
AC
Mitterhofer
Anna Paola
AP
Fiorilli
Massimo
M
Quinti
Isabella
I
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*
D000888:Antibodies, Anti-Idiotypic; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D004247:DNA