院士讲学周课件-银屑病免疫治疗.ppt

1、Mukden Medical School(1891)Manchuria Medical University(1911)China Medical University(1931)in PsoriasisImmunopathogenesis Biologic Therapeutics&Psoriasis is a T cell-mediated disease(a historical perspective)Previously,hyperproliferation and abnormal differentiation of KCs were assumed to be the pri

2、mary defects.Prior therapeutics including retinoids,PUVA,UVB,and MTX,all of which have side effects.Later,it was found that mononuclear cell infiltration appears before epidermal changes.Studies with mAbs showed accumulations of CD4+and CD8+T cells.Accordingly it was suggested that psoriasis might b

3、e a chronic skin inflammation as a result of persistent stimulation of T cells by immunogen of epidermal origin.Several evidences about the role of activated cellular immunity:(1)PUVA depletes T cells;(2)cyclosporine and tacrolimus are effective;(3)flare of symptoms during perturbation of the immune

4、 system or interferon treatment;(4)new lesions are induced by injection of IFN into nonlesional skin of the patient.Subsequent studies demonstrated the predominance of activated Tc1 in the epidermis,activated TH1 in the dermis,the presence of mature LCs,and the expression of CD31,CD34 and PNAd on en

5、dothelial cells,in the psoriatic lesions.From J G Krueger,2002Most direct evidence was the results of DAB389 IL-2(a fusion protein composed of human IL-2 sequence and a fragment of diphtheria toxin)on the treatment of psoriasis.New biologic therapeutics for psoriasisAbs(chimeric,humanized,human sequ

6、ence)fusion proteinsrecombinant cytokinesDesigned to target specific immune-activation steps with least global immune suppression,blocking the cell surface molecules and the cytokines participating in the inflammatory process.From J G Krueger,2002Targeting primary stimulation Targeting costimulation

7、 Targeting T cell proliferative signalsImmune deviation Blockade of effector cytokinesStrategies for Immunobiologic Therapy of PsoriasisM E C H A N ISMN A M EN A T U R ET A R G E TPrevents L Cm aturationPrevents bindingof L FA-1 toIC A M-1efalizum abhum anizal M A bC D 11a(L FA-1 chain)H uM 291hum a

8、nized M A bC D 3 chainB locks T C Rcom plexstim ulationhum anized M A bC D 4Therapeutic Agents Targeting Primary StimulationTherapeutic Agents Targeting CostimulationTherapeutic Agents Targeting T cell Proliferative SignalsTherapeutic Agents for Immune DeviationMECHANISMNATURETARGETrecombinant IL-10

9、recombinant IL-11Stimulates type2 differentiationrecombinant IL-4Suppresses type1 differentiationhumanized MAbIL-12Therapeutic Agents Blocking Effector CytokinesBefore TreatmentAfter TreatmentPublicationsAbout 600 papers published in journals,such as:J Immunol J Invest DermatolArchiv Dermatol Br J D

10、ermatolActa Derm Venereol Dermatol Surg J Am Acad Dermatol J Cutaneous Pathol J Appl Cosmetol Clin Exp DermatolConnect Tissue Res Int J Dermatol Transplantation Dis Markers J Dermatol Int Arch Alle Appl Immunol Tissue Antigens Australasian J DermatolJ Dermatol Science Develop Genetics Chin Med J *Chinese J Dermatol