CYTOKINE PRODUCTION OF B CELL S 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

Neuromuscular junctionVincent A ,

Auto-antibodies in MGAnti-AChR antibody(AP)85-90 %IgG1-2a (Complement activated)Seronegative MG 15-10%Anti-AChR (-) Anti-MuSK (-)(SN)56% 5-8%Anti-MuSK (Muscle specific kinase) (MP)44% 4-6%IgG4 and IgG1 (Complement activity?)

b |Complement C9 deposition in MG

NT: nerve terminal PSF: postsynaptic foldsRole of the complement activation in anti-AChR (+) MG

T cell helpCD40L (Ligand) interactionCytokine

NMean ageImmunosuppressive treatmentMG75502543.133AP37152242.711MP1541139.712SN236174610Rheumatoid Arthritis (RA)2361753.211Controls32161640.6

SUBGROUPS of MG% of CD19+CD27+

p: 0.001p: 0.006SUBGROUPS of MG

p: 0.04p: 0.015

T cell helpCD40L (Ligand) interactionCytokine

BOTH MG and CON were higher than RACON

NO TREATMENTMP> RASN>RAT Cell Help: CD40L expression in CD4+ T cells

CONCON

CONCON

B cell activationB cell receptor (BCR = Ig)Specific antigenAChR/MuSKImmunoglobulinPoly IgT cell helpCD40- CD40L

B cell co-receptors TLRTLR-9CpG/non-CpG

Regulatory Role of B Cells by IL-10 Secretion

AChRMP < CON*RA < CON*IL-6 Response to Specific StimuliNo subgroup related antigen specific responses

No differences in responses to AChR and MuSK between groupsAP MP SN RA CON

CONCLUSIONB cell related or B cell derived cytokine activity in antibody-based subgroups of MG did not reveal a specific pattern for disease developmentThe differences between RA and MG point to differential cytokine effects in these diseasesUntreated patients in all subgroups are needed to clairify the differential features in this disease.

Only RA higher than MG and controlsIL-10Lower in AP compared to RA and ControlsIL-13Higher in RA only

mRNA expression in CD19+ B cells

IL-6 Response to Specific Stimuli in Non-treated Patients

IL-6 Response to Non-specific Stimuli in Non-treated PatientsBasalPoly IgCpG

IL-6 production of B cells in response to specific antigens

TNF-a Response to Non-specific Stimuli in Un-treated Patients

TNFB-

TNFA Antigen-Specific Stimulation