請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/94817完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 周文堅 | zh_TW |
| dc.contributor.advisor | Wen-Chien Chou | en |
| dc.contributor.author | 袁章祖 | zh_TW |
| dc.contributor.author | Chang-Tsu Yuan | en |
| dc.date.accessioned | 2024-08-19T16:56:28Z | - |
| dc.date.available | 2024-08-20 | - |
| dc.date.copyright | 2024-08-19 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-04-26 | - |
| dc.identifier.citation | 1. Döffinger R, Helbert MR, Barcenas-Morales G, et al. Autoantibodies to interferon-gamma in a patient with selective susceptibility to mycobacterial infection and organ-specific autoimmunity. Clin Infect Dis. 2004;38(1):e10-14. doi:10.1086/380453
2. Höflich C, Sabat R, Rosseau S, et al. Naturally occurring anti-IFN-gamma autoantibody and severe infections with Mycobacterium cheloneae and Burkholderia cocovenenans. Blood. 2004;103(2):673-675. doi:10.1182/blood-2003-04-1065 3. Kampitak T, Suwanpimolkul G, Browne S, Suankratay C. Anti-interferon-γ autoantibody and opportunistic infections: case series and review of the literature. Infection. 2011;39(1):65-71. doi:10.1007/s15010-010-0067-3 4. Browne SK, Burbelo PD, Chetchotisakd P, et al. Adult-onset immunodeficiency in Thailand and Taiwan. N Engl J Med. 2012;367(8):725-734. doi:10.1056/NEJMoa1111160 5. Ku CL, Lin CH, Chang SW, et al. Anti-IFN-γ autoantibodies are strongly associated with HLA-DR*15:02/16:02 and HLA-DQ*05:01/05:02 across Southeast Asia. J Allergy Clin Immunol. 2016;137(3):945-948.e8. doi:10.1016/j.jaci.2015.09.018 6. Hong GH, Ortega-Villa AM, Hunsberger S, et al. Natural History and Evolution of Anti-Interferon-γ Autoantibody-Associated Immunodeficiency Syndrome in Thailand and the United States. Clin Infect Dis. 2020;71(1):53-62. doi:10.1093/cid/ciz786 7. Wu UI, Wang JT, Sheng WH, et al. Incorrect diagnoses in patients with neutralizing anti-interferon-gamma-autoantibodies. Clin Microbiol Infect. 2020;26(12):1684.e1-1684.e6. doi:10.1016/j.cmi.2020.02.030 8. Chan JFW, Lau SKP, Yuen KY, Woo PCY. Talaromyces (Penicillium) marneffei infection in non-HIV-infected patients. Emerg Microbes Infect. 2016;5(3):e19. doi:10.1038/emi.2016.18 9. Chi CY, Lin CH, Ho MW, et al. Clinical manifestations, course, and outcome of patients with neutralizing anti-interferon-γ autoantibodies and disseminated nontuberculous mycobacterial infections. Medicine (Baltimore). 2016;95(25):e3927. doi:10.1097/MD.0000000000003927 10. Hase I, Morimoto K, Sakagami T, Ishii Y, van Ingen J. Patient ethnicity and causative species determine the manifestations of anti-interferon-gamma autoantibody-associated nontuberculous mycobacterial disease: a review. Diagn Microbiol Infect Dis. 2017;88(4):308-315. doi:10.1016/j.diagmicrobio.2017.05.011 11. Barcenas-Morales G, Cortes-Acevedo P, Doffinger R. Anticytokine autoantibodies leading to infection: early recognition, diagnosis and treatment options. Curr Opin Infect Dis. 2019;32(4):330-336. doi:10.1097/QCO.0000000000000561 12. Wu UI, Chuang YC, Sheng WH, et al. Use of QuantiFERON-TB Gold In-tube assay in screening for neutralizing anti-interferon-γ autoantibodies in patients with disseminated nontuberculous mycobacterial infection. Clin Microbiol Infect. 2018;24(2):159-165. doi:10.1016/j.cmi.2017.06.029 13. Thingujam B, Syue LS, Wang RC, et al. Morphologic Spectrum of Lymphadenopathy in Adult-onset Immunodeficiency (Anti-interferon-γ Autoantibodies). Am J Surg Pathol. 2021;45(11):1561-1572. doi:10.1097/PAS.0000000000001736 14. Oka K, Yamane M, Yokota Y, et al. Disseminated Mycobacterium genavense infection mimicking TAFRO syndrome. J Infect Chemother. 2020;26(10):1095-1099. doi:10.1016/j.jiac.2020.06.020 15. Nei T, Okabe M, Mikami I, et al. A non-HIV case with disseminated Mycobacterium kansasii disease associated with strong neutralizing autoantibody to interferon-γ. Respir Med Case Rep. 2013;8:10-13. doi:10.1016/j.rmcr.2012.11.003 16. Chen YP, Yen YS, Chen TY, Yen CL, Shieh CC, Chang KC. Systemic Mycobacterium kansasii infection mimicking peripheral T-cell lymphoma. APMIS. 2008;116(9):850-858. doi:10.1111/j.1600-0463.2008.00935.x 17. Liu TT, Weng SW, Wang MC, Huang WT. Nontuberculous mycobacterial infection with concurrent IgG4-related lymphadenopathy. APMIS. 2016;124(3):216-220. doi:10.1111/apm.12492 18. Koizumi Y, Sakagami T, Minamiguchi H, et al. Chylous ascites, anti-interferon-gamma autoantibody, and angioimmunoblastic T-cell lymphoma: a rare but intriguing connection over Mycobacterium avium. Med Microbiol Immunol. 2019;208(1):33-37. doi:10.1007/s00430-018-0555-0 19. Tanigaki T, Kimizuka Y, Maki Y, et al. Development of intravascular large B-cell lymphoma during prophylactic antibiotic treatment for anti-interferon-gamma autoantibody syndrome: A case report. J Infect Chemother. 2022;28(11):1562-1566. doi:10.1016/j.jiac.2022.07.015 20. Chen YC, Weng SW, Ding JY, et al. Clinicopathological Manifestations and Immune Phenotypes in Adult-Onset Immunodeficiency with Anti-interferon-γ Autoantibodies. J Clin Immunol. 2022;42(3):672-683. doi:10.1007/s10875-022-01210-y 21. Yuan CT, Wang JT, Sheng WH, et al. Lymphadenopathy Associated With Neutralizing Anti-interferon-gamma Autoantibodies Could Have Monoclonal T-cell Proliferation Indistinguishable From Malignant Lymphoma and Treatable by Antibiotics: A Clinicopathologic Study. Am J Surg Pathol. 2021;45(8):1138-1150. doi:10.1097/PAS.0000000000001731 22. EuroClonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferations - PubMed. Accessed January 13, 2024. https://pubmed.ncbi.nlm.nih.gov/22918122/ 23. Kuo FC, Hall D, Longtine JA. A novel method for interpretation of T-cell receptor gamma gene rearrangement assay by capillary gel electrophoresis based on normal distribution. J Mol Diagn. 2007;9(1):12-19. doi:10.2353/jmoldx.2007.060032 24. Lee SC, Berg KD, Racke FK, Griffin CA, Eshleman JR. Pseudo-spikes are common in histologically benign lymphoid tissues. J Mol Diagn. 2000;2(3):145-152. doi:10.1016/S1525-1578(10)60630-7 25. Cesano A. nCounter(®) PanCancer Immune Profiling Panel (NanoString Technologies, Inc., Seattle, WA). J Immunother Cancer. 2015;3:42. doi:10.1186/s40425-015-0088-7 26. R Core Team. R: A language and environment for statistical computing. Published online 2022. Accessed December 31, 2023. https://www.R-project.org/ 27. RStudio Team. RStudio: Integrated Development Environment for R. Published online 2022. Accessed December 31, 2023. http://www.rstudio.com/ 28. Wickham H. Ggplot2: Elegant Graphics for Data Analysis. Springer-Verlag; 2016. Accessed December 31, 2023. https://ggplot2.tidyverse.org 29. Warnes G, Bolker B, Bonebakker L, et al. gplots: Various R Programming Tools for Plotting Data. Published online 2022. Accessed December 31, 2023. https://CRAN.R-project.org/package=gplots 30. Day A. heatmap.plus: Heatmap with more sensible behavior. Published online 2012. Accessed December 31, 2023. https://CRAN.R-project.org/package=heatmap.plus 31. Benjamini Y, Yekutieli D. The control of the false discovery rate in multiple testing under dependency. The Annals of Statistics. 2001;29(4):1165-1188. doi:10.1214/aos/1013699998 32. Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545-15550. doi:10.1073/pnas.0506580102 33. Danaher P, Warren S, Dennis L, et al. Gene expression markers of Tumor Infiltrating Leukocytes. J Immunother Cancer. 2017;5:18. doi:10.1186/s40425-017-0215-8 34. Ritchie ME, Phipson B, Wu D, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47. doi:10.1093/nar/gkv007 35. Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012;16(5):284-287. doi:10.1089/omi.2011.0118 36. Dolgalev I. msigdbr: MSigDB Gene Sets for Multiple Organisms in a Tidy Data Format. Published online 2022. Accessed December 31, 2023. https://CRAN.R-project.org/package=msigdbr 37. Davoli T, Uno H, Wooten EC, Elledge SJ. Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy. Science. 2017;355(6322):eaaf8399. doi:10.1126/science.aaf8399 38. Nakajima S, Kaneta A, Okayama H, et al. The Impact of Tumor Cell-Intrinsic Expression of Cyclic GMP-AMP Synthase (cGAS)-Stimulator of Interferon Genes (STING) on the Infiltration of CD8+ T Cells and Clinical Outcomes in Mismatch Repair Proficient/Microsatellite Stable Colorectal Cancer. Cancers (Basel). 2023;15(10):2826. doi:10.3390/cancers15102826 39. Chan JKC, Kwong YL. Common misdiagnoses in lymphomas and avoidance strategies. Lancet Oncol. 2010;11(6):579-588. doi:10.1016/S1470-2045(09)70351-1 40. Campo E, Jaffe ES, Cook JR, et al. The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee. Blood. 2022;140(11):1229-1253. doi:10.1182/blood.2022015851 41. Megan Lim, John Chan, Sandeep S. Dave, et al. nodal TFH cell lymphoma, angioimmunoblastic-type. In: WHO Classification of Tumours Editorial Board. Haematolymphoid Tumours [Internet; Beta Version Ahead of Print]. 5th ed. International Agency for Research on Cancer. https://tumourclassification.iarc.who.int/chaptercontent/63/240 42. Gratzinger D, Jaffe ES, Chadburn A, et al. Primary/Congenital Immunodeficiency: 2015 SH/EAHP Workshop Report-Part 5. Am J Clin Pathol. 2017;147(2):204-216. doi:10.1093/ajcp/aqw215 43. Tran H, Nourse J, Hall S, Green M, Griffiths L, Gandhi MK. Immunodeficiency-associated lymphomas. Blood Rev. 2008;22(5):261-281. doi:10.1016/j.blre.2008.03.009 44. Facchetti F, Blanzuoli L, Ungari M, Alebardi O, Vermi W. Lymph node pathology in primary combined immunodeficiency diseases. Springer Semin Immunopathol. 1998;19(4):459-478. doi:10.1007/BF00792602 45. Suresh PK, Poojary S, Basavaiah SH, Kini JR, Lobo FD, Sahu KK. Utility of fine-needle aspiration cytology in the diagnosis of HIV lymphadenopathy. Diagn Cytopathol. 2019;47(10):1011-1017. doi:10.1002/dc.24255 46. Więsik-Szewczyk E, Jahnz-Różyk K. From infections to autoimmunity: Diagnostic challenges in common variable immunodeficiency. World J Clin Cases. 2020;8(18):3942-3955. doi:10.12998/wjcc.v8.i18.3942 47. Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood. 2017;129(12):1646-1657. doi:10.1182/blood-2016-10-746933 48. Wallace ZS, Naden RP, Chari S, et al. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease. Ann Rheum Dis. 2020;79(1):77-87. doi:10.1136/annrheumdis-2019-216561 49. Cheuk W, Yuen HKL, Chu SYY, Chiu EKW, Lam LK, Chan JKC. Lymphadenopathy of IgG4-related sclerosing disease. Am J Surg Pathol. 2008;32(5):671-681. doi:10.1097/PAS.0b013e318157c068 50. Tsuyama N, Sakamoto K, Sakata S, Dobashi A, Takeuchi K. Anaplastic large cell lymphoma: pathology, genetics, and clinical aspects. J Clin Exp Hematop. 2017;57(3):120-142. doi:10.3960/jslrt.17023 51. Langerak AW, Groenen PJ, Jm van Krieken JH, van Dongen JJ. Immunoglobulin/T-cell receptor clonality diagnostics. Expert Opin Med Diagn. 2007;1(4):451-461. doi:10.1517/17530059.1.4.451 52. Yu F, Ba X, Yang H, et al. Kikuchi disease with an exuberant proliferation of large T-cells: a study of 25 cases that can mimic T-Cell lymphoma. Histopathology. 2023;82(2):340-353. doi:10.1111/his.14821 53. Liao F, Rabin RL, Yannelli JR, Koniaris LG, Vanguri P, Farber JM. Human Mig chemokine: biochemical and functional characterization. J Exp Med. 1995;182(5):1301-1314. doi:10.1084/jem.182.5.1301 54. Ohmori Y, Schreiber RD, Hamilton TA. Synergy between interferon-gamma and tumor necrosis factor-alpha in transcriptional activation is mediated by cooperation between signal transducer and activator of transcription 1 and nuclear factor kappaB. J Biol Chem. 1997;272(23):14899-14907. doi:10.1074/jbc.272.23.14899 55. Muehlinghaus G, Cigliano L, Huehn S, et al. Regulation of CXCR3 and CXCR4 expression during terminal differentiation of memory B cells into plasma cells. Blood. 2005;105(10):3965-3971. doi:10.1182/blood-2004-08-2992 56. Rani MR, Foster GR, Leung S, Leaman D, Stark GR, Ransohoff RM. Characterization of beta-R1, a gene that is selectively induced by interferon beta (IFN-beta) compared with IFN-alpha. J Biol Chem. 1996;271(37):22878-22884. doi:10.1074/jbc.271.37.22878 57. Qian C, An H, Yu Y, Liu S, Cao X. TLR agonists induce regulatory dendritic cells to recruit Th1 cells via preferential IP-10 secretion and inhibit Th1 proliferation. Blood. 2007;109(8):3308-3315. doi:10.1182/blood-2006-08-040337 58. Ohnishi K, Ichikawa A, Kagami Y, et al. Interleukin 4 and gamma-interferon may play a role in the histopathogenesis of peripheral T-cell lymphoma. Cancer Res. 1990;50(24):8028-8033. 59. Pizzolo G, Stein H, Josimovic-Alasevic O, et al. Increased serum levels of soluble IL-2 receptor, CD30 and CD8 molecules, and gamma-interferon in angioimmunoblastic lymphadenopathy: possible pathogenetic role of immunoactivation mechanisms. Br J Haematol. 1990;75(4):485-488. doi:10.1111/j.1365-2141.1990.tb07786.x 60. Gupta M, Stenson M, O’Byrne M, et al. Comprehensive serum cytokine analysis identifies IL-1RA and soluble IL-2Rα as predictors of event-free survival in T-cell lymphoma. Ann Oncol. 2016;27(1):165-172. doi:10.1093/annonc/mdv486 61. Iqbal J, Weisenburger DD, Greiner TC, et al. Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma. Blood. 2010;115(5):1026-1036. doi:10.1182/blood-2009-06-227579 62. Lee SK, Silva DG, Martin JL, et al. Interferon-γ excess leads to pathogenic accumulation of follicular helper T cells and germinal centers. Immunity. 2012;37(5):880-892. doi:10.1016/j.immuni.2012.10.010 63. Ohshima K, Tutiya T, Yamaguchi T, et al. Infiltration of Th1 and Th2 lymphocytes around Hodgkin and Reed-Sternberg (H&RS) cells in Hodgkin disease: Relation with expression of CXC and CC chemokines on H&RS cells. Int J Cancer. 2002;98(4):567-572. doi:10.1002/ijc.10218 64. Goncharova O, Flinner N, Bein J, et al. Migration Properties Distinguish Tumor Cells of Classical Hodgkin Lymphoma from Anaplastic Large Cell Lymphoma Cells. Cancers (Basel). 2019;11(10):1484. doi:10.3390/cancers11101484 65. Krishnan C, Warnke RA, Arber DA, Natkunam Y. PD-1 expression in T-cell lymphomas and reactive lymphoid entities: potential overlap in staining patterns between lymphoma and viral lymphadenitis. Am J Surg Pathol. 2010;34(2):178-189. doi:10.1097/PAS.0b013e3181cc7e79 66. Egan C, Laurent C, Alejo JC, et al. Expansion of PD1-positive T Cells in Nodal Marginal Zone Lymphoma: A Potential Diagnostic Pitfall. Am J Surg Pathol. 2020;44(5):657-664. doi:10.1097/PAS.0000000000001414 67. Xie Y, Jaffe ES. How I Diagnose Angioimmunoblastic T-Cell Lymphoma. Am J Clin Pathol. 2021;156(1):1-14. doi:10.1093/ajcp/aqab090 68. Weiss LM, O’Malley D. Benign lymphadenopathies. Mod Pathol. 2013;26 Suppl 1:S88-96. doi:10.1038/modpathol.2012.176 69. Cheuk W, Chan JKC. Lymphadenopathy of IgG4-related disease: an underdiagnosed and overdiagnosed entity. Semin Diagn Pathol. 2012;29(4):226-234. doi:10.1053/j.semdp.2012.07.001 70. Mattoo H, Mahajan VS, Maehara T, et al. Clonal expansion of CD4(+) cytotoxic T lymphocytes in patients with IgG4-related disease. J Allergy Clin Immunol. 2016;138(3):825-838. doi:10.1016/j.jaci.2015.12.1330 71. Chen Y, Lin W, Yang H, et al. Aberrant Expansion and Function of Follicular Helper T Cell Subsets in IgG4-Related Disease. Arthritis Rheumatol. 2018;70(11):1853-1865. doi:10.1002/art.40556 72. Guihot A, Oksenhendler E, Galicier L, et al. Multicentric Castleman disease is associated with polyfunctional effector memory HHV-8-specific CD8+ T cells. Blood. 2008;111(3):1387-1395. doi:10.1182/blood-2007-03-080648 73. Mumau M, Pierson SK, Gonzalez M, Canna S, Fajgenbaum DC. Serum Proteomics Identifies Interferon Gamma Signaling in Idiopathic Multicentric Castleman Disease. Blood. 2022;140(Supplement 1):5500-5501. doi:10.1182/blood-2022-167829 74. Taylor GS, Long HM, Brooks JM, Rickinson AB, Hislop AD. The immunology of Epstein-Barr virus-induced disease. Annu Rev Immunol. 2015;33:787-821. doi:10.1146/annurev-immunol-032414-112326 75. Shi Y, Lutz CT. Interferon--gamma control of EBV-transformed B cells: a role for CD8+ T cells that poorly kill EBV-infected cells. Viral Immunol. 2002;15(1):213-225. doi:10.1089/088282402317340350 76. Steed AL, Barton ES, Tibbetts SA, et al. Gamma interferon blocks gammaherpesvirus reactivation from latency. J Virol. 2006;80(1):192-200. doi:10.1128/JVI.80.1.192-200.2006 77. Cacoub P, Musette P, Descamps V, et al. The DRESS syndrome: a literature review. Am J Med. 2011;124(7):588-597. doi:10.1016/j.amjmed.2011.01.017 78. Gru AA, O’Malley DP. Autoimmune and medication-induced lymphadenopathies. Semin Diagn Pathol. 2018;35(1):34-43. doi:10.1053/j.semdp.2017.11.015 79. Farhi DC, Mason UG, Horsburgh CR. Pathologic findings in disseminated Mycobacterium avium-intracellulare infection. A report of 11 cases. Am J Clin Pathol. 1986;85(1):67-72. doi:10.1093/ajcp/85.1.67 80. Kraus M, Benharroch D, Kaplan D, et al. Mycobacterial cervical lymphadenitis: the histological features of non-tuberculous mycobacterial infection. Histopathology. 1999;35(6):534-538. doi:10.1046/j.1365-2559.1999.00787.x 81. Jarzembowski JA, Young MB. Nontuberculous mycobacterial infections. Arch Pathol Lab Med. 2008;132(8):1333-1341. doi:10.5858/2008-132-1333-NMI | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/94817 | - |
| dc.description.abstract | 成人發病的免疫缺陷症候群，其特徵為中和抗丙型干擾素自體抗體（AIGA），常常帶來診斷上的挑戰，往往導致誤診。其中一種突出的表現為發燒性淋巴結腫大，需要進行全面的臨床病理分析，以釐清AIGA患者淋巴結腫大的複雜情況。此外，由於AIGA的非特異性臨床表現以及與某些淋巴瘤類型相似，包括淋巴濾泡輔助細胞型T細胞淋巴瘤-血管免疫芽型（nTFHL-AI），對AIGA的診斷也變得困難。
首先，我們進行了一項回顧性病例系列，分析與AIGA相關的淋巴結腫大，涵蓋了來自一家醫療中心的16名AIGA患者的26個淋巴結樣本。所有患者同時出現全身性非結核分枝桿菌感染，其中31％最初被臨床診斷為淋巴瘤。組織形態學模式分為良好形成的肉芽腫（46％），化膿性炎症或組織細胞凝集（31％）和淋巴增生性疾患（LPD）（23％）。 AIGA-LPD呈現異質性，可能與惡性T細胞淋巴瘤、IgG4相關疾病和多中心Castleman病相似。 LPD樣本的一半具有單株T細胞，其中33.3％與nTFHL-AI難以區分。抗生素治療導致LPD特徵消散，無需進行細胞毒性化療或免疫治療，對於惡性診斷產生疑慮。中位追蹤時間為4.3年。 接著，為了找出可靠的診斷方法，我們將研究人口擴大到一項多機構病例對照研究，包括13例AIGA-LPD和24例nTFHL-AI。首先，通過使用NanoString nCounter平台進行全癌病原體免疫分析，我們發現CXCL9和PDCD1在AIGA中的表達明顯下調，相較於nTFHL-AI。 CXCL9免疫組織化學（IHC）證實其在高診斷準確性（92.3％敏感性，100％特異性）方面區分AIGA-LPD和nTFHL-AI的能力。 總之，在AIGA的背景下區分淋巴瘤和良性淋巴腫大仍然是一項挑戰。全面的臨床病理分析強調了在臨床醫生和病理學家之間進行更多警覺和多學科討論的必要性，以獲得最佳的診斷和管理。 CXCL9的下調成為區分AIGA和nTFHL-AI等相似狀況的強大生物標記，提供可靠的診斷方法，以防止誤診，確保及時和準確的診斷。 | zh_TW |
| dc.description.abstract | Adult-onset immunodeficiency associated with neutralizing anti-interferon γ autoantibodies (AIGA) presents diagnostic challenges, often resulting in misdiagnoses. One of its prevalent manifestations is febrile lymphadenopathy, necessitating a comprehensive clinicopathological analysis to unravel the complexities of lymphadenopathy in AIGA patients. Additionally, diagnosing AIGA proves challenging due to its nonspecific clinical presentation and its resemblance to certain lymphoma types, including nodal T follicular helper cell lymphoma, angioimmunoblastic type (nTFHL-AI).
Firstly, we conducted a retrospective case series analyzing AIGA-related lymphadenopathy, encompassing 26 lymph node biopsy specimens from 16 AIGA patients in a single medical center. All patients presented with concurrent disseminated nontuberculous mycobacterial infections, with 31% initially receiving a clinical diagnosis of lymphoma. Histomorphological patterns were categorized into well-formed granuloma (46%), suppurative inflammation or histiocytic aggregates (31%), and lymphoproliferative disorder (LPD) (23%). AIGA-LPD exhibits heterogeneity and can resemble malignant T-cell lymphoma, IgG4-related disease, and multicentric Castleman disease. Half of the LPD specimens featured monoclonal T cells, with 33% indistinguishable from nTFHL-AI. Antibiotic treatment led to the regression of LPD features without the need for cytotoxic chemotherapy or immunotherapy, casting doubt on a malignant diagnosis. The median follow-up time was 4.3 years. Next, to identify reliable diagnostic methods, we expanded the study population into a multi-institutional case-control study involving 13 AIGA-LPD and 24 nTFHL-AI cases. Initially, through immune transcriptomic analysis with the NanoString nCounter platform using PanCancer immune profiling, we discovered significant downregulation of CXCL9 and PDCD1 compared to nTFHL-AI. CXCL9 immunohistochemistry demonstrated its ability to differentiate AIGA-LPD from nTFHL-AI with high diagnostic accuracy (92% sensitivity, 100% specificity). In conclusion, differentiating between lymphoma and benign lymphadenopathy in the context of AIGA remains a challenge. The comprehensive clinicopathological analysis underscores the necessity for increased vigilance and multidisciplinary discussions among clinicians and pathologists for optimal diagnosis and management. The downregulation of CXCL9 emerges as a robust biomarker for differentiating AIGA from nTFHL-AI and similar conditions, providing a reliable diagnostic approach to prevent misdiagnosis and ensure a timely and accurate diagnosis. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-08-19T16:56:28Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-08-19T16:56:28Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
誌謝 ii 中文摘要 iii Abstract iv 目次 v 圖次 viii 表次 ix Chapter 1. Introduction 1 1.1 Neutralizing anti-interferon γ autoantibodies (AIGA) represent a significant etiological factor in the onset of adult immunodeficiency in Taiwan 1 1.2 Detection of neutralizing AIGA is not routinely available 1 1.3 AIGA-related lymphadenopathy: resemblance to various lymphoproliferative disorders and lymphomas with a challenge in reliable distinction 2 1.4 Aim and study objectives: comprehensive description of AIGA-related lymphadenopathy and discovery of robust distinction strategies to prevent misdiagnosis 2 Chapter 2. Material and Methods 4 2.1 Cohort and specimen collection 4 2.2 Clinical information 4 2.3 Detection of AIGA 5 2.4 Histomorphological analysis 6 2.5 Immunohistochemical study and chromogenic in situ hybridization 7 2.6 T-cell clonality assay through receptor gene rearrangement 7 2.7 Immune transcriptomes of AIGA-related lymphadenopathy and nTFHL-AI 8 2.8 Serum CXCL9 level using Enzyme-Linked-Immunosorbent Assay 8 2.9 Statistical and bioinformatic analysis 8 Chapter 3. Results 11 3.1 Part I: Clinical analysis of patients with AIGA 11 3.2 Part I: Histopathological analysis of AIGA-related lymphadenopathy 12 3.3 Part I: The misleading lymphoproliferative pattern in AIGA-related lymphadenopathy 13 3.4 Part I: Relationship between histological pattern and detection of acid-fast bacilli 15 3.5 Part I: Follow-up and prognosis 15 3.6 Part II: Clinicopathological analysis and discriminative features of AIGA-LPD and nTFHL-AI 16 3.7 Part II: Transcriptomic analysis reveals reduced CD4+ helper T cell population and CXCL9 downregulation in AIGA-LPD compared to nTFHL-AI 17 3.8 Part II: CXCL9 immunohistochemistry as a robust biomarker for discriminating AIGA-LPD from nTFHL-AI 18 3.9 Part II: Diagnostic utility of CXCL9 immunohistochemistry in distinguishing AIGA from pathological mimickers 18 Chapter 4. Discussion 20 4.1 Summary of study findings 20 4.2 Clues to differentiate AIGA-related lymphadenopathy from lymphoma with similar clinicopathological features 20 4.3 Reassessment of concurrent AIGA and lymphoma diagnoses in the literature 21 4.4 CXCL9 as a distinct marker correlating with AIGA in contrast to other interferon-γ stimulating cytokines 22 4.5 Elevated CXCL9 expression in lymphomas with comparable clinicopathological features to AIGA 22 4.6 Challenges in using PD1 to differentiate AIGA from nTFHL-AI 23 4.7 Distinguishing IgG4-related lymphadenopathy from AIGA-related lymphadenopathy 24 4.8 Exclusion of AIGA before diagnosing idiopathic multicentric Castleman disease 24 4.9 Miscellaneous conditions with similar histomorphology to AIGA-related lymphadenopathy 25 4.10 Unraveling the enigma of lymphoproliferation mechanism in AIGA-related lymphadenopathy 26 4.11 Application of CXCL9 immunohistochemistry for AIGA screening in routine practice amidst disseminated nontuberculous mycobacterial Infection 26 Chapter 5. Conclusions 28 5.1 Novelty and implication summary 28 5.2 Limitations 28 5.3 Future perspectives 30 參考文獻 32 附錄1. 圖 40 附錄2. 表 62 附錄3. 著作列表 80 | - |
| dc.language.iso | zh_TW | - |
| dc.title | 避免中和抗丙型干擾素自體抗體導致的淋巴結病變在病理學上被誤診為淋巴瘤 | zh_TW |
| dc.title | Mitigating Pathological Misdiagnosis of Lymphoma in Lymphadenopathy due to Neutralizing Anti-Interferon Gamma Autoantibodies | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.coadvisor | 胡婉妍 | zh_TW |
| dc.contributor.coadvisor | Un-In Wu | en |
| dc.contributor.oralexamcommittee | 莊世松;葉秀慧;黃凱文;葉士芃 | zh_TW |
| dc.contributor.oralexamcommittee | Shih-Sung Chuang;Shiou-Hwei Yeh;Kai-Wen Huang;Shih-Peng Yeh | en |
| dc.subject.keyword | 中和抗丙型干擾素自體抗體,全身性非結核分枝桿菌感染,血管免疫芽型 T 細胞淋巴瘤,IgG4 相關淋巴腫大,多中心 Castleman 病, | zh_TW |
| dc.subject.keyword | neutralizing anti-interferon-gamma autoantibody,disseminated nontuberculous mycobacterial infection,angioimmunoblastic T-cell lymphoma,IgG4-related lymphadenopathy,multicentric Castleman disease, | en |
| dc.relation.page | 83 | - |
| dc.identifier.doi | 10.6342/NTU202400876 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2024-04-29 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 臨床醫學研究所 | - |
| 顯示於系所單位： | 臨床醫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-112-2.pdf 授權僅限NTU校內IP使用（校園外請利用VPN校外連線服務） | 7.21 MB | Adobe PDF | 檢視/開啟 |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。