Decrease in circulating DNA, IL-10 and BAFF levels in newly-diagnosed SLE patients after corticosteroid and chloroquine treatment

Cepika, Alma-Martina; Soldo Jureša, Dragica; Morović Vergles, Jadranka; Malenica, Branko; Šantak, Maja; Kapitanović, Sanja; Mayer, Miro; Anić, Branimir; Sentić, Mirna; Gagro, Alenka

doi:10.1016/j.cellimm.2012.05.009

Pregled bibliografske jedinice broj: 537080

Decrease in circulating DNA, IL-10 and BAFF levels in newly-diagnosed SLE patients after corticosteroid and chloroquine treatment

Cepika, Alma-Martina; Soldo Jureša, Dragica; Morović Vergles, Jadranka; Malenica, Branko; Šantak, Maja; Kapitanović, Sanja; Mayer, Miro; Anić, Branimir; Sentić, Mirna; Gagro, Alenka

Decrease in circulating DNA, IL-10 and BAFF levels in newly-diagnosed SLE patients after corticosteroid and chloroquine treatment // Cellular immunology, 276 (2012), 1/2; 196-203 doi:10.1016/j.cellimm.2012.05.009 (međunarodna recenzija, članak, znanstveni)

CROSBI ID: 537080 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
Decrease in circulating DNA, IL-10 and BAFF levels in newly-diagnosed SLE patients after corticosteroid and chloroquine treatment

Autori
Cepika, Alma-Martina ; Soldo Jureša, Dragica ; Morović Vergles, Jadranka ; Malenica, Branko ; Šantak, Maja ; Kapitanović, Sanja ; Mayer, Miro ; Anić, Branimir ; Sentić, Mirna ; Gagro, Alenka

Izvornik
Cellular immunology (0008-8749) 276 (2012), 1/2; 196-203

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
systemic lupus erythematosus; TLR9; circulating DNA; CpG; IL-10; BAFF

Sažetak
Arsenal of pattern-recognition receptors alongside antibody production machinery make B cells vulnerable to autoimmune response if in autoantigenelicits 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 TLR) 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 3 weeks on corticosteroids, and 3 months 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 immunomodualtory treatment prompts for inclusion of untreated patients in studies of human immune disorders.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Kliničke medicinske znanosti

POVEZANOST RADA

Projekti:
021-0212432-3123 - Molekularna patogeneza virusa mumpsa (Šantak, Maja, MZOS ) ( CroRIS)
072-1080229-0337 - Modulacija funkcije ljudskih regulacijskih T-limfocita (Gagro, Alenka, MZOS ) ( CroRIS)
098-0982464-2508 - Molekularna genetika i farmakogenetika gastrointestinalnih tumora (Kapitanović, Sanja, MZOS ) ( CroRIS)
108-1081874-2419 - Epidemiološka obilježja sistemskog eritemskog lupusa u Hrvatskoj (Čikeš, Nada, MZOS ) ( CroRIS)
198-1081874-0183 - Patogeneza sustavnih poremećaja u reumatoidnom artritisu (Morović-Vergles, Jadranka, MZOS ) ( CroRIS)
214-1081874-0168 - Regulacijski limfociti u sistemskim autoimunim bolestima (Malenica, Branko, MZOS ) ( CroRIS)

Ustanove:
Imunološki zavod d.d.,
Klinika za dječje bolesti Medicinskog fakulteta,
Institut "Ruđer Bošković", Zagreb,
Medicinski fakultet, Zagreb,
Klinička bolnica "Dubrava",
Klinički bolnički centar Zagreb

Profili:

Branko Malenica (autor)