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.
Regression of Systemic Lupus Erythematosus After Development of an Acquired Toll-like Receptor Signaling Defect and Antibody Deficiency / Visentini, Marcella; Conti, Valentina; Cagliuso, Maria; Tinti, Francesca; Siciliano, Giulia; Amelia C., Trombetta; Mitterhofer, Anna Paola; Fiorilli, Massimo; Quinti, Isabella. - In: ARTHRITIS AND RHEUMATISM. - ISSN 0004-3591. - 60:9(2009), pp. 2767-2771. [10.1002/art.24760]