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CYTOKINE PRODUCTION OF B CELL S OF MYASTHENIA GRAVIS PATIENTS

CYTOKINE PRODUCTION OF B CELL S OF MYASTHENIA GRAVIS PATIENTS. V. Yilmaz 1 , P. Oflazer 2 , F. Aysal 3 , Y.G. Parman 2 , H. Direskeneli 4 , F. Deymeer 2 , G. Saruhan-Direskeneli 1 I.U. Istanbul Medical Faculty Departments of Physiology and Neurology,

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CYTOKINE PRODUCTION OF B CELL S OF MYASTHENIA GRAVIS PATIENTS

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  1. CYTOKINE PRODUCTION OF B CELLS OF MYASTHENIA GRAVIS PATIENTS V. Yilmaz1, P. Oflazer2, F. Aysal3, Y.G. Parman2, H. Direskeneli4, F. Deymeer2, G. Saruhan-Direskeneli1 I.U. Istanbul Medical Faculty Departments of Physiology and Neurology, (3)Bakirkoy Hospital (4) Marmara University, Faculty of Medicine, Division of Rheumatology, Istanbul/Turkey

  2. Neuromuscular junction Vincent A ,

  3. Auto-antibodies in MG • Anti-AChRantibody(AP) 85-90 % IgG1-2a (Complementactivated) • Seronegative MG 15-10% • Anti-AChR (-) Anti-MuSK (-) (SN) 56% 5-8% • Anti-MuSK (Musclespecifickinase) (MP) 44% 4-6% IgG4 and IgG1 (Complementactivity?)

  4. Role of Cytokines in Regulation of AntibodyProduction • T cellhelp • CD40L (Ligand) interaction • Cytokine

  5. Basal Cytokine Secretion of PBMC in MG IFNg IL-10 IL-13 * p<0.001 * p< 0.001 N 59 22 MG CON N 59 22 MG CON N 59 22 MG CON PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC)

  6. CD3 Stimulation of MG PBMC IL-10 IFNg IL-13 *p<0.001 *p=0.001 N 25 16 18 SN MP AP N 25 16 18 SN MP AP N 25 16 18 SN MP AP

  7. StudyGroup

  8. B Cells in thePeriphery % of CD19+CD27+ SUBGROUPS of MG

  9. BAFF RECEPTOR (BAFFR) in MG p: 0.006 p: 0.001 SUBGROUPS of MG

  10. T HelperCells (Th2): CD4+CCR4+ p: 0.015 p: 0.04

  11. Role of Cytokines in Regulation of AntibodyProduction • T cellhelp • CD40L (Ligand) interaction • Cytokine

  12. T CellHelp: CD40L expression in isolated CD4+ T cells CON BOTH MG and CON were higher than RA

  13. T CellHelp: IL-10 and IFN-gexpression in isolated CD4+ T cells CON CON

  14. IL-10 and IL-6 expression in isolated CD19+ B cells CON CON

  15. B cell activation • B cellreceptor (BCR = Ig) SpecificantigenAChR/MuSK ImmunoglobulinPolyIg • T cellhelp CD40- CD40L • B cellco-receptors TLR TLR-9 CpG/non-CpG

  16. TLR Stimulation of B Cells

  17. Regulatory Role of B Cells by IL-10 Secretion

  18. IL-10 ResponsetoNonspecificStimuli Basal: SN<CON* MP<CON* RA<CON* AP<CON Poly Ig: SN<CON* RA<CON* MP<CON AP<CON Basal Poly Ig CpG

  19. IL-10 production of B cells in response to specific antigens AChR: MP<CON* RA<CON* SN<CON AP<CON Basal tAChR rMuSK No subgroup related antigen specific responses

  20. IL-6 ResponsetoNon-specificStimuli Basal: MP<CON* RA<CON* AP<CON SN<CON Poly Ig: MP<CON* AP<CON* RA<CON* SN<CON Basal Poly Ig CpG

  21. IL-6 Response to Specific Stimuli AChR MP < CON* RA < CON* No subgroup related antigen specific responses

  22. TNF-aResponsetoStimulation Poly Ig: MP<CON* SN<CON* Basal Poly Ig CpG No differences in responses to AChR and MuSK between groups

  23. TNF-bResponsetoNon-specificStimuli Basal: MP<CON* AP<CON* RA<CON* Poly Ig: MP<CON* SN>CON Basal Poly Ig CpG

  24. TNF-bResponseto SpecificStimuli AChR: RA<CON* No subgroup related antigen specific responses Basal tAChR rMuSK

  25. IL-12p40 Secretion in ResponsetoNon-specificStimulation AP MP SN RA CON No differences in responses to AChR and MuSK between groups

  26. CONCLUSION • B cellrelatedor B cellderivedcytokineactivity in antibody-basedsubgroups of MG did not reveal a specificpatternfordiseasedevelopment • Thedifferencesbetween RA and MG pointtodifferentialcytokineeffects in thesediseases • Untreatedpatients in allsubgroupsareneededtoclairifythedifferentialfeatures in thisdisease.

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