KISEP 40 8 1997 돌발성난청의병인에서면역계의역할에관한연구 Abstract 여상원 박용수 김규식 장기홍 Role of Immune System in the Pathogenesis of Sudden Deafness Sang Won Yeo, M.D., Yong Soo Park, M.D., Que Chic Kim, M.D., Ki Hong Chang, M.D. Department of Otolaryngology, College of Medicine, The Catholic University, Seoul, Korea To evaluate the immunological role in the etiopathogenesis of sudden deafness, sera from 44 patients with sudden sensorineural hearing loss were analyzed by 1 immunologic screening tests such as erythrocyte sedimentation rateesr, C-reactive proteincrp, immunoglobulinigg, IgM levels, complementc3, C4 levels, autoantibodyrheumatoid factor, anti-dna antibody, antinuclear antibody levels, cryoglobulin and FTA-ABS 2 Western blotting immunoassay against cows inner ear proteins 3 viral marker assayserum IgG and IgM titer against cytomegalovirus, herpes simplex virus, varicella-zoster virus, measles virus, mumps virus and rubella virus. Thirteen29.5% of 44 patients displayed positive responses on immunologic screening tests. Significantly higher incidences of immunological abnormalities were found in the parameters such as levels of IgG, ESR, IgM and anti-nuclear antibody. Of 41 patients whose sera were analyzed by Western blot against fresh bovine inner ear antigen preparation, nobody showed the antibody against 68kD protein, and 12.4%, 49.8%, and 49.8% had antibody which reacted with 60kD, 50kD and 3335kD protein. On viral marker assay, 844.4% of 18 patients showed positive IgG titers against herpes simplex virus, cytomegalovirus, varicella-zoster virus, measles virus, mumps virus and rubella virus. But any of 10 patients did not show significant IgM titers against those viruses. Statistical analysis revealed a significant correlation between the results of immunologic screening tests and the age of the patientsp0.05 by chi-square, but no correlations with other clinical parameters such as sex, bilaterality, initial hearing level, and recoveryp0.05 by chi-square respectively. There was no correlation between the results of viral marker assayigg and recoveryp0.05 by chisquare. The results suggest that viral infection may play a role in development and progress of sudden 1181
40 8 1997 deafness, while the immunologic disorder may not affect the etiopathogenesis of sudden deafness. Korean J Otolaryngol 408, 1997 KEY WORDSSudden deafness Immunologic screening tests Western blotting immunoassay Viral marker assay. 서 론 재료및방법 1. 환자 1182
Korean J Otolaryngol 408, August 1997 Table 1. Type of hearing recoverysiegel s criteria and results of treatmentn50 Type of hearing recovery No. of pts% Complete recovery Final hearing better than 25dB 1020.0 Partial recovery More than 15dB gain and final hearing 2545dB 1224.0 Slight improvement More than 15dB gain and final hearing poorer than 45dB 3 6.0 No improvement Less than 15dB gain or final hearing poorer than 75dB 2550.0 ptspatients. 2. 면역학적선별검사 (Immunologic Screening Tests) 3. Western Blotting Immunoassay 1) 항원의추출 2) SDS-PAGE 3) Western Blotting 1183
40 8 1997 4. Viral marker assay 5. 치료 6. 통계분석 결과 1. 면역학적선별검사 (Immunologic Screening Tests) 2. Western Blotting Immunoassay 3. Viral marker assay Table 2. Results of immmuologic screening testsn44 IgG ESR IgM ANA C3 C4 CRP RF No. of pts% 1943.2 1534.1 511.4 36.8 24.5 24.5 12.3 12.3 IgGimmunoglobulin G, ESRerythrocyte sedimentation rate, IgMimmunoglobulin M, ANAanti-nuclear antibody, C3 & C4complement 3 & 4, CRPC-reactive protein, RFrheumatoid factor, ptspatients. 1184
Korean J Otolaryngol 40 8, August 1997 Fig. 1. Immunoblots of sera from patients with sudden deafness. Lane a means molecular weight marker. Lane d, g, i and j show a band at 60kD. Lane c, f and m disclose a band at 50kD and lane d, h and n display a band at 33 35kD. However a band at 68kD is not seen. Table 3. Positive results from viral marker(igg) test (n 18) HSV CMV VZV Measles Mumps Rubella No. of pts(%) 5(27.8) 4(22.2) 3(16.7) 3(16.7) 2(11.1) 1(5.6) HSV herpes simplex virus, CMV cytomegalovirus, VZV varicella-zoster virus, Measles measles virus, Mumps mumps virus, Rubella rubella virus. virus(3명), measles virus(3명), mumps virus(2명), rubella virus(1명)의 순이었다(Table 3). IgM 항체 역가는 검사를 시행했던 10명의 환자 모두에서 음성 으로 나타났다. Table 4. Results of immunologic tests in different sex group(n 44)(p>0.05) Sex Male Female 4. 검사 결과와 임상 양상과의 상관관계 1) 면역학적 선별검사와 임상 양상과의 관계 Total Positive(%) Negative(%) Total(%) 10(22.7) 17(38.6) 27( 61.4) 3( 6.8) 14(31.8) 17( 38.6) 13(29.5) 31(70.5) 44(100.0) 편측성으로 발병한 경우가 13례, 양측성으로 발병한 경우는 없었으며 음성으로 나타났던 31명중에 편측성 (1) 면역학적 선별검사와 성별 으로 발병한 경우가 29례, 양측성으로 발병한 경우가 면역학적 선별검사상 양성으로 나타났던 13명중에 2례로 면역학적 선별검사 결과와 편측 혹은 양측성 는 남자가 10명, 여자가 3명이었고 음성으로 나타났 발병 여부 간에는 유의한 상관관계가 존재하지 않았 던 31명중에는 남자가 17명, 여자가 14명으로서 면 다(p>0.05)(Table 5). 역학적 선별검사 결과와 환자의 성별 사이에는 유의 한 상관관계가 존재하지 않았다(p> 0.05)(Table 4). (2) 면역학적 선별검사와 편측 혹은 양측성 발병 (3) 면역학적 선별검사와 연령 면역학적 선별검사 결과와 환자의 발병 연령과는 통계적으로 유의한 상관관계가 존재했는데(p<0.05), 특히 60대 이후에 면역학적 검사상 양성으로 나타나 면역학적 선별검사상 양성으로 나타났던 13명중에 는 경우가 많았고 40 60세에서는 오히려 음성으로 1185
40 8 1997 Table 5. Correlation between results of immunologic tests and bilateralityn44p0.05 Positive% Negative% Total% Unilateral Rt 818.1 1022.7 18 40.9 Lt 511.4 1943.2 24 54.5 Bilateral 0 0 2 4.5 24.5 Total% 1329.5 3170.5 44100.0 Table 6. Results of immunologic tests in different age groupn44p0.05 Age Positive% Negative% Total% 10 0 0 2 4.5 2 4.5 11 20 1 2.3 0 0 1 2.3 21 30 0 0 715.9 715.9 31 40 3 6.8 3 6.8 613.6 41 50 1 2.3 715.9 818.2 51 60 1 2.3 818.2 920.5 61 70 4 9.1 4 9.1 818.2 71 3 6.8 0 0 3 6.8 Total% 1329.5 3170.5 44100.0 Table 7. Correlation between results of immunologic tests and initial pure tone audiometry thresholdn46p0.05 Hearing loss Positive% Negative% Total% Mild 2 4.3 4 8.7 613.0 Moderate 2 4.3 1328.3 1532.6 Moderate-severe 510.9 613.0 1123.9 Severe 3 6.5 613.0 919.6 Profound 1 2.2 4 8.7 510.9 Total% 1328.3 3371.7 46100.0 (4) 면역학적선별검사와초기청력 (5) 면역학적선별검사와회복정도 Table 8. Correlation between results of immunologic tests and recoveryn46p0.05 Recovery Positive% Negative% Total% Complete 2 4.3 817.4 1021.7 Partial 4 8.7 613.0 1021.7 Slight 1 2.2 1 2.2 2 4.3 No recovery 613.0 1839.1 2452.2 Total% 1328.3 3371.7 46100.0 Table 9. Correlation between viral markerigg and recoveryn18p0.05 Viral markerigg Recovery % No recovery % Total% Positive 633.3 211.1 844.4 Negative 527.8 527.8 1055.6 Total% 1161.1 738.9 18100.0 2) Viral marker(igg) 와예후와의관계 고찰 1186
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요약 Korean J Otolaryngol 408, August 1997 References 1) 여상원, 노혜일, 정대건등 : 내이질환환자에서내이자가면역에대한연구. 한이인지. 1995;38:163-175 2) 이재행, 김주현, 이근평등 : 돌발성난청의임상적분석. 한이인지. 1990;33:690-697 3) 전경명 : 돌발성난청의실제. 제69차대한이비인후과추계학술대회숙제보고, 정명당, 1995 4) Harris JP, Sharp PA:Inner ear autoantibodies in patients with rapidly progressive sensorineural hearing loss. Laryngoscope. 1990;100:516-524 5) Hughes GB, Barna BP:Autoimmune inner ear disease:fact or fantasy? Adv Otorhinolaryngol. 1991;46:82-91 6) Hughes GB, Barna BP, Kinney SE, et al:predictive value of laboratory tests in autoimmune inner ear disease:a preliminary report. Laryngoscope. 1986;96:502-505 7) Kanzaki J, Inoue Y, O-uchi T:Immunological findings of serological tests in steroid-responsive sensorineural hearing loss. Acta Otolaryngol(Stockh) Suppl. 1994;514:66-69 8) Laemmli UK:Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680-685 9) Lehnhardt E:Pltzliche hrstrungen, auf beiden seiten gleichzeitig oder nacheinander aufgetrenten. Z Laryngol Rhinol Otol. 1958;37:1-17 10) McCabe BF:Autoimmune sensorineural hearing loss. Ann Otol Rhinol Laryngol. 1979;88:585-589 11) Moscicki RA, Ramadan H, Castro OJ, et al:corticosteroid response and immunologic studies in idiopathic progressive sensorineural hearing loss. J Allergy Clin Immunol. 1988;81:217 12) Moscicki RA, San Martin JE, Quintero CH, et al: Serum antibody to inner ear proteins in patients with progressive hearing loss, correlation with disease activity and response to corticosteroid treatment. JAMA. 1994;272(8):611-616 13) Rowson KEK, Hinchcliffe R, Gamble DR:A virological and epidemiological study of patients 1189
40 8 1997 with acute hearing loss. The Lancet. 1975;138: 471-473 14) Schuknecht HF, Donovan ED:The pathology of sudden sensorineural hearing loss. Arch Otorhinolaryngol. 1986;243:1-15 15) Siegel LG:The treatment of idiopathic sudden sensorineural hearing loss. Otolaryngol Clin North Am. 1975;8(2):467-473 16) Suzuki M, Kitahara M:Immunologic abnormality in Meniere s disease. Otolaryngol Head Neck Surg. 1992;107:57-62 17) Towbin H, Staehelin T, Gordon J:Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets:procedure and some applications. Proc Natl Acad Sci USA. 1979;76: 4350-4356 18) Van Dishoeck HAE, Bierman TA:Sudden perceptive deafness and viral infection. Ann Otol Rhinol Laryngol. 1957;66:936-980 19) Veldman JE, Hanada T, Meeuwsen F:Diagnostic and therapeutic dilemmas in rapidly progressive sensorineural hearing loss and sudden deafness. A reappraisal of immune reactivity in inner ear disorders. Acta Otolaryngol(Stockh). 1993;113: 303-306 20) Wilson WR, Byl FM, Laird N:The efficacy of steroids in the treatment of idiopathic sudden hearing loss:a double-blind clinical study. Arch Otolaryngol. 1980;106:772-776 21) Wilson WR, Gulya AJ:Sudden sensorineural hearing loss. In:Cummings CE, eds. Otolaryngology-Head and Neck Surgery. St. Louis, New York:Mosby Year Book, 1993:3103-3112 22) Yamanobe S, Yagi T, Kosaka K:Inner ear autoantibodies in patients with Meniere s disease or sudden deafness. In Immunobiology in Otorhinolaryngology-Progress of a decade(ed. Mogi G et al). Amsterdam/New york, Kugler Pub, 1994: 247-249 23) Yoon TH, Paparella MM, Schachern PA, et al: Histopathology of sudden hearing loss. Laryngoscope. 1990;100:707-714 1190