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; Trombetta, A.C.; Mitterhofer, Anna Paola; Fiorilli, Massimo; Quinti, Isabella

doi:10.1002/art.24760

Cited by 23 publications

(17 citation statements)

References 16 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have demonstrated that anti-nucleic acid immune complexes, isolated from the sera of SLE patients, stimulate plasmacytoid dendritic cells (pDCs) to produce IFN-a (19,20). Mean et al (21) have reported that DNA-containing immune complexes, but not protein-containing immune complexes, stimulate pDCs to produce cytokines, including IFN-a, TNF, and IL-8.…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 9 in systemic lupus erythematosus, impact on glucocorticoid treatment

Ghaly

Kotb

Nagy

et al. 2012

Journal of Dermatological Treatment

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 9 in systemic lupus erythematosus, impact on glucocorticoid treatment

Ghaly

Kotb

Nagy

et al. 2012

Journal of Dermatological Treatment

View full text Add to dashboard Cite

show abstract

“…IFNα is critical player in SLE progression and severity, and has been shown to induce the production of autoantibodies when administered to non-SLE patients (12, 51). An interesting report describes remission of SLE in a patient which was attributed to unresponsiveness to both TLR-7 and -9 stimulation after development of common variable immunodeficiency – (CVID-) like disease (52). Genetic variations in many of the components of the TLR signaling pathway have been associated with SLE, such as TLR-7, IRF5, IRF7, IRF8, IRAK1, and TNFAIP3 (53–59).…”

Section: Genetic Factors Associated With Tlr-dependent Ifnα Pathway Imentioning

confidence: 99%

Nucleic Acid Sensors and Type I Interferon Production in Systemic Lupus Erythematosus

Shrivastav¹,

Niewold²

2013

Front. Immunol.

View full text Add to dashboard Cite

The characteristic serologic feature of systemic lupus erythematosus (SLE) is autoantibodies against one’s own nucleic acid or nucleic acid-binding proteins – DNA and RNA-binding nuclear proteins. Circulating autoantibodies can deposit in the tissue, causing inflammation and production of cytokines such as type 1 interferon (IFN). Investigations in human patients and animal models have implicated environmental as well as genetic factors in the biology of the SLE autoimmune response. Viral/Bacterial nucleic acid is a potent stimulant of innate immunity by both toll-like receptor (TLR) and non-TLR signaling cascades. Additionally, foreign DNA may act as an immunogen to drive an antigen-specific antibody response. Self nucleic acid is normally restricted to the nucleus or the mitochondria, away from the DNA/RNA sensors, and mechanisms exist to differentiate between foreign and self nucleic acid. In normal immunity, a diverse range of DNA and RNA sensors in different cell types form a dynamic and integrated molecular network to prevent viral infection. In SLE, pathologic activation of these sensors occurs via immune complexes consisting of autoantibodies bound to DNA or to nucleic acid-protein complexes. In this review, we will discuss recent studies outlining how mismanaged nucleic acid sensing networks promote autoimmunity and result in the over-production of type I IFN. This information is critical for improving therapeutic strategies for SLE disease.

show abstract

“…Furthermore, IVIG attenuates Toll-like receptor 9 (TLR9) responses through the recruitment of the inhibitory SHP-1 phosphatase [36]. Inhibition of TLR9-mediated B cell activation could be an important mechanism of the immunoregulatory effects of IVIG in autoimmune disorders [37,38].…”

Section: Discussionmentioning

confidence: 99%

Intravenous immunoglobulin replacement therapy in common variable immunodeficiency induces B cell depletion through differentiation into apoptosis-prone CD21low B cells

et al. 2014

Self Cite

View full text Add to dashboard Cite

Intravenous immunoglobulin (IVIG), besides its use as replacement therapy in patients with antibody deficiencies, is broadly used as an immunomodulatory agent for the treatment of autoimmune and inflammatory disorders. The mechanisms of action of IVIG include Fc receptor blockade, inhibition of cytokines and growth factors, modulation of macrophages and dendritic cells, enhancement of regulatory T cells, and modulation of B cells through the FcγRIIB receptor and CD22. Recent studies suggest that in vitro exposure of human B cells to IVIG determines functional changes reminiscent of anergy and that IVIG treatment of patients with common variable immunodeficiency (CVID) induces in B cells ERK activation, a feature of anergy. Here, we show that IVIG therapy drives the B cells of patients with CVID to down-regulate CD21 expression and to assume the peculiar phenotype of the anergic-like, apoptosis-prone CD21(low) B cells that are spontaneously expanded in a subset of CVID and in some other immunological disorders. The CD21(low) B cells newly generated after IVIG infusion undergo spontaneous apoptosis upon in vitro culture. Furthermore, IVIG infusion is rapidly followed by a significant, although discrete, decrease in the number of circulating B cells, but not of T cells or of natural killer cells. These findings suggest that IVIG therapy may constrain antibody responses by inducing B cell depletion through differentiation into CD21(low) B cells that undergo accelerated apoptosis.

show abstract

Regression of systemic lupus erythematosus after development of an acquired Toll‐like receptor signaling defect and antibody deficiency

Cited by 23 publications

References 16 publications

Toll-like receptor 9 in systemic lupus erythematosus, impact on glucocorticoid treatment

Toll-like receptor 9 in systemic lupus erythematosus, impact on glucocorticoid treatment

Nucleic Acid Sensors and Type I Interferon Production in Systemic Lupus Erythematosus

Intravenous immunoglobulin replacement therapy in common variable immunodeficiency induces B cell depletion through differentiation into apoptosis-prone CD21low B cells

Contact Info

Product

Resources

About