Decrease in circulating DNA, IL-10 and BAFF levels in newly-diagnosed SLE patients after corticosteroid and chloroquine treatment.
Arsenal of pattern-recognition receptors alongside antibody production machinery make B cells vulnerable to autoimmune response if an autoantigen elicits both pathways in a self-sustained fashion. Systemic lupus erythematosus is an autoimmune disease characterized by autoantibodies to DNA, RNA and related structures. Murine studies demonstrated autoreactive B cell activation upon TLR9 stimulation with DNA-containing immune complexes. This activation could be abolished with chloroquine, a drug used in SLE treatment that also blocks TLR9 signaling. We investigated whether chloroquine modulates TLR9 expression, circulating DNA levels and B cell-related cytokines in newly discovered, untreated SLE patients. TLR9 was measured in peripheral blood B cells by flow cytometry, serum DNA by real-time PCR, and IL-10 and BAFF by ELISA before treatment, after 3weeks on corticosteroids, and 3months after introduction of chloroquine. We found that circulating DNA is higher in SLE patients than in controls in every time-point and decreases significantly after chloroquine treatment. Untreated patients had higher serum IL-10 than controls or patients on corticosteroids. Also, corticosteroids decreased and chloroquine completely abolished CpG-mediated CD86 upregulation on B cells and IL-10 secretion in PBMC culture. Providing the TLR9 pathway activation demonstrates its importance in pathogenesis of human SLE, this data supports continuation of chloroquine in SLE treatment protocol. In addition, observed modulation of cytokine and DNA levels after immunomodulatory treatment prompts for inclusion of untreated patients in studies of human immune disorders.
Department of Pediatrics, Children's Hospital Zagreb, Klaiceva 16, 10000 Zagreb, Croatia. acepika@gmail.com
Alma-Martina
AM
Cepika
Dragica
D
Soldo Jureša
Jadranka
J
Morović Vergles
Branko
B
Malenica
Maja
M
Santak
Sanja
S
Kapitanović
Miroslav
M
Mayer
Branimir
B
Anić
Mirna
M
Sentić
Alenka
A
Gagro
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D053264:B-Cell Activating Factor / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D002738:Chloroquine / Q000627:therapeutic use*; D004247:DNA / Q000276:immunology*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D018501:Antirheumatic Agents; D053264:B-Cell Activating Factor; C508609:IL10 protein, human; C505719:TNFSF13B protein, human; D016753:Interleukin-10; D002738:Chloroquine; D004247:DNA