Pulsatile TH2 Shift Of Recovering TCR-Vβ Expanded T-Helper Effector Cells After Initiation Of IVIG Treatment in CIDP (P1.074)

Objective: To investigate the impact of intravenous immunoglobulins (IVIg) on T cell (TC) activation and differentiation in TC-receptor (TCR) restricted TC in chronic inflammatory demyelinating polyneuropathy (CIDP). Background: CIDP is an acquired chronic autoimmune disease of the peripheral nervous system, which can be successfully treated with IVIg. Many efforts have been made to elucidate IVIg’s therapeutical mechanisms. Although T-cells mediate the link between humoral und cellular immunity, profound data on IVIg actions on TC in CIDP remain sparse. Design/Methods: PBL from n=30 patients with CIDP were analyzed longitudinally by FACS-Immunophenotyping, CDR3-Spectratyping and Cytokine-ELISA after initiation and during maintenance IVIg treatment. Results: We found a recovery of individually expanded T-cell-receptor repertoire after IVIg-treatment initiation. Providing a deeper insight into immunomodulation our data indicate that these suppressive actions are accompanied by a shift from a pro-inflammatory TH1 to an anti-inflammatory TH2 cytokine milieu (FACS, ELISA). We here provide evidence, that a mature (CD45RO+CD45RA-CD62lowCD28low) and highly activated (LFA-1highVLA-4high) TH1 cell (CCR4highCCR5low) subpopulation, which carries a single patient-specific TCR-vβ chain, is suppressed during IVIg-therapy. As correlated with a significant increase in serum TH2 index cytokine IL-4 levels 2 weeks after IVIg-initiation, this might contribute to therapeutic effects regarding anti- inflammation and clinical restitution in CIDP. In addition, deviations in serum cytokine milieu refer also to TH1 and TH17 index cytokines INF-γ and IL-17. Conclusions: As IL-4 serum levels are found to be markedly high only in short intervals (2 weeks) after IVIg-administration, correlating with patients’ clinical improvement, and then decrease until the next, therapeutical benefits might be due to a pulsatile TH2 induction. This TH2 shift might lead to a short-term restitution of serum milieu and cellular immunehomeostasis, that, in contrast, cannot overcome pathological autoimmunity, necessitating maintenance therapy, as seen in clinical practice. To our knowledge, this TC subset characterization is the first to contribute to functional relevance of TCR repertoire recovery by IVIg. Disclosure: Dr. Russwurm has nothing to disclose. Dr. Putz has nothing to disclose. Dr. Hoft has nothing to disclose. Dr. Schlegel has nothing to disclose. Dr. Happel has nothing to disclose. Dr Eienbroker has received personal compensation for activities with Biogen Idec, Novartis, and Temmler Pharma. Dr Seipelt has received personal compensation for activities with Biogen Idec, Genzyme Corp. and Novartis. Dr. Tackenberg has received personal compensation for activities with Bayer Pharmaceuticals Corp., Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience. Dr. Tackenberg has received research support from Bayer Pharmaceuticals Corp., Biogen Idec, and Novartis.