KISEP Information Korean J Otolaryngol 2005;48:1312-22 이재서 Immunotherapy for Allergic Rhinitis:Current and Future Chae-Seo Rhee, MD Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, Korea 1312
이재서 Patient presents with allergic rhinitis for which immunotherapy may be appropriate Evidence of specific IgE antibodies? Test results correlate with clinical symptoms and exposure No Not a condidate for immunotherapy Yes Assess Risks and benefits of appropriate management options Immunotherapy Allergen exposure reduction Medications Patient preferences Response to previous treatment Severity of disease Is immunotherapy recommended for this patient? No Immunotherapy not given Yes Obtain informed consent Counsel and educate patient about the benefits and risks of immunotherapy Identify Specific allergen vaccines Starting dose and immunotherapy schedule Maintenance dose Administer Immunotherapy Safety equipment and procedures in place Twenty-to 30-minute wait in office after injection Consideration of peak flow rate Reaction to Immunotherapy injection? Yes Manage reaction Assess immunotherapy Consider dose or schedule adjustment Consider discontinuing immunotherapy No Assess at follow-up Clinical response to immunotherapy e.g., symptoms, medication use Immunotherapy schedule, reactions, compliance Continuation/discontinuation of immunotherapy treatment Fig. 1. Algorithm for allergen immunotherapy Adapted from Ann Allergy Asthma Immunol 200390 1-40 알레르겐의선택 치료스케줄 1313
Table 1. Recommended maintenance doses of allergen immunotherapy Allergen Dose, standardized units Dose, major allergen Maintenance concentrate, wt/vol* Dermatophagoides pteronyssinus 600 AU 712 g Der p 1 NA Dermatophagoides farinae 2,000 AU 10 g Der f 1 NA Cat 2,0003,000 BAU 1117 g Fel d 1 NA Grass e.g., timothy 4,000 BAU 7 g Phl p 5 NA Short ragweed standardized NA 624 g Amb a 1 1100130 Other pollen nonstandardized NA ND 1100130 Fungi/mold nonstandardized NA ND 1100150 Based on a maintenance injection of 0.5 ml. AUallergy unit, BAUbioequivalent allergy unit, NAnot applicable, NDnot determined 1314 Table 2. Sample buildup schedule for weekly immunotherapy Dilution, vol/vol Volume, ml 11,000 0.05 0.10 0.30 0.50 1100 0.05 0.10 0.20 0.30 0.40 110 0.50 0.05 0.10 0.20 0.30 0.35 0.40 0.45 0.50 Maintenance concentrate 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50 Dilutions are expressed as volume per volume from the maintenance concentrate vaccine. Korean J Otolaryngol 2005;48:1312-22
이재서 Table 3. Sample schedule for cluster immunotherapy comparing with conventional schedule Week Cluster schedule Conventional schedule Dose BU Total dose BU Total dose g of Der p 1 Dose BU Total dose BU Total dose g of Der p 1 00 0.02 00.2 00.08 0.01 00.01 0.004 0.04 0.06 0.08 01 0.10 00.9 00.36 0.02 00.03 0.012 0.20 0.40 02 0.60 02.3 00.92 0.04 00.07 0.028 0.80 03 1.00 05.3 02.12 0.08 00.15 0.060 2.00 04 2.00 10.3 04.12 0.10 00.25 0.100 3.00 05 3.00 17.3 06.92 0.20 00.45 0.180 4.00 06 8.00 25.3 10.12 0.40 00.85 0.340 07 0.00 25.3 10.12 0.80 01.65 0.660 08 0.00 25.3 10.12 100. 02.65 1.060 09 0.00 25.3 10.12 200. 04.65 1.860 10 0.00 25.3 10.12 400. 08.65 3.460 11 0.00 25.3 10.12 600. 14.65 5.860 12 0.00 25.3 10.12 800. 22.65 9.060 Interval of injection30 minutes. Only placebo doses were administered to the cluster group from weeks 7 to 12. The maintenance immunotherapy doses were administered at weeks 15 and 18 and were continued every 4 weeks up to the end of 1 year. 1315
Antigen Presenting Cell CD4 CD25 IL-10 TGF- IgE IgG4 IgA IT IL-4 Allergic Response IT IL-5 Fig. 2. Summary of the effects of immunotherapy on T-cell responses. T regt regulatory cell, DC dendritic cell, EOSeosinophil Adapted from J Allergy Clin Immunol 20041131025-34. IFN- NH2 NH2 Reactive to NH2 Reactive to SH SH FcRI expression and IgE-dependent mast cell activation Eosinophil survival and activation ssmcc CD4 + CD25 + IL-10 A Antigen ISS-ODN IgG4 IgE-dependent antigen presentation IL-10 and cell contact Ag ISSAg C-ODNAg Western Cytokines and proliferation Fig. 3. Summary of the potential antiallergic properties of IL-10 on different limbs of the allergic immune response. EOSeosinophil, T regt regulatory cell Adapted from J Allergy Clin Immunol 20041131025-34 T-lymphocyte response 1316 B UV shadow Fig. 4. Synthesis of antigen ISS-ODN conjugates AICs. AAICs are synthesized by using sulfosuccinimidyl-4-[n-maleimidomethyl]- cyclohexane-1-carboxylate ssmcc to chemically cross-link NH2 groups on protein antigen with sulfhydryl SH groups on ODNs. BVisualization of antigen Ag, ISS-ODNAg conjugate ISS Ag, and control ODNAg conjugate C-ODNAg by Western blot after sodium dodecyl sulfate polyacrylamide gel electrophoresis shows higher molecular weight bands for the conjugates compared to native protein. The ODNs contained in the conjugates are also visible by ultraviolet UV shadowing of the gel Adapted from Immunol Rev 2004199217-26 Korean J Otolaryngol 2005;48:1312-22
이재서 in vitro 항체반응의변화 (Changes in antibody response) - 1317
SLIT 1318 Korean J Otolaryngol 2005;48:1312-22
이재서 경구투여면역요법 비내면역요법 저용량면역요법 (low dose immunotherapy) - - - Recombinant peptide 1319
- DNA vaccine Adjuvant - - - 항 IgE 항체 CXCR4 AMD3100 T-Lymphocyte Th1 augmentation IFN- IL-12 CpG immunotherapy IL-18 Signaling molecules T-bet GATA-3 STAT-6 Anti-CD11a antibody CD11a Th2 inhibition IL-4 antagonist Anti IL-5 antibody IL-13 Fig. 5. Many immunomodulation targets have some regulatory effect on T-lymphocyte function. Experimental and theoretical targets include augmenting the T helper type 1 response or inhibiting the T helper type 2 response through cytokines, cytokine receptors, chemokine receptors, or signaling molecules. Other targets may include adhesion molecules, such as CD11a, to decrease the extravasation of effector lymphocytes into tissues Adapted from Curr Opin Allergy Clin Immunology 2004463-7 1320 Korean J Otolaryngol 2005;48:1312-22
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