S102 Abstracts

F.83. Examination Profile of IL-6 and TNF-α inRF-positive Patients with Rheumatoid ArthritisDuring Infliximab TreatmentLudmila Siziakina, Tatiana Kalashnikova. Rostov StateMedical University, Rostov-on-Don, Russian Federation

Rheumatoid arthritis (RA) is a chronic autoimmune diseasewith destructive lesions of peripheral joints. It have beenshown that IL-1, IL-6 and TNF-α are the most importantinflammatory cytokines in rheumatoid synovium. The firstanti-TNF drug approved for clinical use was infliximab (Inx),unfortunately, 30% of the patients are primary non-respon-ders. The aim of our researchwas to examine the profile of IL-6 and TNF-α in RF-positive positive patients with rheumatoidarthritis during infliximab treatment. Materials andmethods.The study included 28 patients (22 females, 6 males) with RF-positive variant of RA, mean age of 42,6±2,8 years, durationof a disease is 7,2±1,4 years. All patients received combinedtherapy with methotrexate (MT-12,5-15 mg) and Inx whichwas injected at single dose of 3 mg/kg intravenously,followed by administration 2 and 6 weeks later, and repeatedevery 8 weeks (6 infusions). Efficiency of the therapy wasestimated according to DAS28 4V Index and improvementcriteria of EULAR. Regular examination of patients includeddynamics TNF-α and IL-6 of serum and supernatants whichwas determined in ELISA, the quantity of lymphocytesexpressing receptors to TNF-α (CD120a). Results. Two groupsof patients have been estimated depending on EULARimprovement criteria of therapy after 6th infusions: I groupwith a good response and II group with moderate response orno response. Conclusion. Non-responders have initial in-creased IL-6 and TNF-α in serum, it was initial increased PHA-stimulated production of TNF-α and IL-6 by PMBC andCD120a-lymphocytes not determined in a blood.

doi:10.1016/j.clim.2010.03.305

F.84. Impaired T Cell Receptor Activation inIRAK-4-Deficient PatientsDouglas McDonald1, Frederick Goldman3, Oscar Gomez2,Andrew Issekutz4, Dinakantha Kumararatne5, Raif Geha1.1Children's Hospital, Boston, Boston, MA; 2University ofIowa Children's Hospital, Iowa City, IA; 3Children's Hospitalof Alabama, Birmingham; 4Dalhousie University, Halifax,NS, Canada; 5Addenbrooke's Hospital, Cambridge, UnitedKingdom

IRAK4 is a protein kinase effector of the Toll-like receptor(TLR) and interleukin 1 receptor pathways which plays acritical role in innate immune responses. The role of IRAK-4 inadaptive immune functions in humans is incompletely under-stood. We evaluated T cell receptor (TCR) function in fourIRAK-4-deficient patients. We compared upregulation of CD25and CD69 on T cells and production of the cytokines IL-2, IL-6,and IFNγ in anti-CD3 plus anti-CD28 stimulated PBMCs fromfour IRAK-4-deficient patients and four normal controls.Upregulation of CD25 and CD69 on T cells was significantlyreduced in the IRAK-4-deficient patients compared to normalcontrols following cross-linking with anti-CD3 plus anti-CD28.

Production of IL-6 (patients=210 pg/ml vs. normals=7000 pg/ml, pb0.05) and IFNγ (patients=777 pg/ml vs. normals=72000 pg/ml, pb0.05), but not IL-2 (patients=5200 pg/ml vs.normals=7250 pg/ml, p=n.s.), by PBMCs was reduced in IRAK-4-deficient patients compared to normal controls followingcross-linking with anti-CD3 plus anti-CD28. IRAK-4-deficientpatients have defects in T cell activation and TCR-induced cy-tokine production. Defects in T cell activation may contributeto the infectious susceptibilities of IRAK-4-deficient patients.

doi:10.1016/j.clim.2010.03.306

F.85. Dexamethasone Pretreatment Followed byan Inoculation of Short-termLipopolysaccharide-stimulated Dendritic Cells Improvesthe Response of Murine Collagen-induced ArthritisJuan Aguillon, Maria Peña, Diego Catalan, Octavio Aravena,Nicole Rojas-Colonelli, David Garate. Universidad de Chile,Santiago, Chile

Pharmacologically modulated dendritic cells (DCs) havebeen shown to restore tolerance in collagen (CII)-inducedarthritis (CIA). We examined the effect of dexamethasone(DXM) administration as a conditioning agent, followed by aninjection of lipopolysaccharide (LPS)-stimulated and CII-loadedDCs on the CIA course. After CIA induction, mice pre-treatedwith DXM were injected with 4-hour LPS-stimulated bone mar-row derived-DCs loaded with CII (DXM/4hLPS/CII/DCs) or leftunloaded (DXM/4hLPS/DCs). Mice inoculated with DXM/4hLPS/CII/DCs displayed significantly less severe clinical diseasecompared to animals receiving 4hLPS/CII/DCs alone or thosein which only DXM was given. Cytokine profile evaluation dem-onstrated that CD4+ T lymphocytes from DXM/4hLPS/CII/DCsand 4hLPS/CII/DCs groups released higher IL-10 levels thanthose of the DXM group or those of the CIA group. CD4+ T cellsfrom all DC-treated groups showed less IL-17 release whencompared to the CIA group. On the contrary, CD4+ T lym-phocytes from 4hLPS/CII/DCs and DXM/4hLPS/CIIC/DCs groupsreleased higher IFN-γ levels than those from DXM (Pb0.01) orCIA groups. Finally, we conclude that a combined treatment, in-cludingDXMpreconditioning followedbyan inoculation of short-term LPS-stimulated DCs, provides an improved strategy formodulating CIA. The benefit is driven by IL-10 producing CD4+ Tlymphocytes, which interfere with IL-17 production.

Supported by Fondecyt-Chile 107-0553 and MillenniumNucleus on Immunology and Immunotherapy-Chile P07-088-F.

doi:10.1016/j.clim.2010.03.307

F.86. Nascent Multiple Sclerosis Lesions areAssociated with Early Disturbances in theBlood–brain BarrierJorge Alvarez, Alisha Godschalk, Simone Terouz, AlexandrePrat. University of Montreal, Montreal, QC, Canada

Early changes in the normal appearing white matter of MSpatients precede the appearance of gadolinium-enhancing