作者投稿
专家审稿
编辑办公
邮件订阅
RSS
-
摘要: 自身免疫性疾病(autoimmune disease, AID)发病机制复杂。近年来，越来越多的证据表明，感染在驱动具有潜在遗传背景的AID的发生和进展中起关键作用，这为临床重新审视AID的诱因及可能机制提供了更广阔和新颖的视角。本文通过总结病原微生物与自身免疫/AID相关性的最新研究进展，旨在从病原学角度探讨常见AID的病因和发病机制，以期通过整合现有证据，加深对AID发病机制的认识，为疾病预防和临床诊疗提供有价值的见解。Abstract: The pathogenesis of autoimmune diseases (AID) is a complex process. In recent years, an increasing number of evidence has shown that infection plays a key role in driving the occurrence and progression of AID, particularly in individuals with underlying genetic predisposition. This provides a new and broader perspective for clinical examination of the causes and potential mechanisms of AID. In this review, we aim to summarize the latest research progress on the relationship between pathogenic microorganisms and autoimmunity/AID, with the goal of exploring the etiology and pathogenesis of common AID from an etiological perspective. By integrating existing evidence, we hope to deepen the understanding of AID pathogenesis and provide valuable insights for disease prevention, clinical diagnosis and treatment.
-
Key words:
- autoimmunity /
- pathogenesis /
- pathogenic microorganisms /
- molecular mimicry /
- SARS-CoV-2
作者贡献：程琳琳、李詹负责查阅文献、撰写及修订论文；李永哲负责修订论文、终审及校对。利益冲突：所有作者均声明不存在利益冲突 -
表 1 自身免疫性疾病及相关病原微生物
疾病分类 相关病原微生物 器官特异性自身免疫性疾病 1型糖尿病[3] 肠道病毒/菌群，巨细胞病毒 原发性胆汁性胆管炎[4] 大肠埃希菌，幽门螺杆菌 多发性硬化症[5] EB病毒，巨细胞病毒，人疱疹病毒6型，水痘-带状疱疹病毒 系统性自身免疫性疾病 系统性红斑狼疮[6] EB病毒，水痘带状疱疹病毒，人乳头状瘤病毒，轮状病毒，肠道病毒，人内源性逆转录病毒，登革热病毒，肠道菌群，弓形虫 类风湿关节炎[7] EB病毒，巨细胞病毒，人内源性逆转录病毒，人乳头瘤病毒，胃肠道/口腔菌群 白塞病[8] 链球菌，结核分枝杆菌，幽门螺杆菌，肠道/口腔菌群，疱疹病毒科 系统性硬化症[9] EB病毒，细小病毒B19，幽门螺杆菌，巨细胞病毒，人疱疹病毒6型，逆转录病毒 干燥综合征[10] EB病毒，细小病毒B19，丙型肝炎病毒，人疱疹病毒6型，巨细胞病毒，人嗜T淋巴球病毒1型，共生菌 
下载: 导出CSV
-
[1] Pisetsky DS. Pathogenesis of autoimmune disease[J]. Nat Rev Nephrol, 2023, 19: 509-524. [2] Hussein HM, Rahal EA. The role of viral infections in the development of autoimmune diseases[J]. Crit Rev Microbiol, 2019, 45: 394-412. doi: 10.1080/1040841X.2019.1614904 [3] Goldberg E, Krause I. Infection and type 1 diabetes mellitus-a two edged sword?[J]. Autoimmun Rev, 2009, 8: 682-686. doi: 10.1016/j.autrev.2009.02.017 [4] Kumagi T, Abe M, Ikeda Y, et al. Infection as a risk factor in the pathogenesis of primary biliary cirrhosis: pros and cons[J]. Dis Markers, 2010, 29: 313-321. doi: 10.1155/2010/791310 [5] Khalesi Z, Tamrchi V, Razizadeh MH, et al. Association between human herpesviruses and multiple sclerosis: A systematic review and meta-analysis[J]. Microb Pathog, 2023, 177: 106031. doi: 10.1016/j.micpath.2023.106031 [6] Quaglia M, Merlotti G, De Andrea M, et al. Viral Infections and Systemic Lupus Erythematosus: New Players in an Old Story[J]. Viruses, 2021, 13: 277. doi: 10.3390/v13020277 [7] Gremese E, Tolusso B, Bruno D, et al. Infectious agents breaking the immunological tolerance: The holy grail in rheumatoid arthritis reconsidered[J]. Autoimmun Rev, 2022, 21: 103102. doi: 10.1016/j.autrev.2022.103102 [8] Cheng L, Zhan H, Liu Y, et al. Infectious agents and pathogenesis of Behçet's disease: An extensive review[J]. Clin Immunol, 2023, 251: 109631. doi: 10.1016/j.clim.2023.109631 [9] Soldan SS, Lieberman PM. Epstein-Barr virus and multiple sclerosis[J]. Nat Rev Microbiol, 2023, 21: 51-64. doi: 10.1038/s41579-022-00770-5 [10] Björk A, Mofors J, Wahren-Herlenius M. Environmental factors in the pathogenesis of primary Sjögren's syndrome[J]. J Intern Med, 2020, 287: 475-492. doi: 10.1111/joim.13032 [11] Rojas M, Restrepo-Jiménez P, Monsalve DM, et al. Molecular mimicry and autoimmunity[J]. J Autoimmun, 2018, 95: 100-123. doi: 10.1016/j.jaut.2018.10.012 [12] Cunningham MW. Molecular Mimicry, Autoimmunity, and Infection: The Cross-Reactive Antigens of Group A Streptococci and their Sequelae[J]. Microbiol Spectr, 2019, 7: 10.1128/microbiolspec.GPP3-0045-2018. doi: 10.1128/microbiolspec.GPP3-0045-2018 [13] Lee H, Jeong S, Shin EC. Significance of bystander T cell activation in microbial infection[J]. Nat Immunol, 2022, 23: 13-22. doi: 10.1038/s41590-021-00985-3 [14] Cornaby C, Gibbons L, Mayhew V, et al. B cell epitope spreading: mechanisms and contribution to autoimmune diseases[J]. Immunol Lett, 2015, 163: 56-68. doi: 10.1016/j.imlet.2014.11.001 [15] Christen U. Pathogen infection and autoimmune disease[J]. Clin Exp Immunol, 2019, 195: 10-14. [16] Nekoua MP, Alidjinou EK, Hober D. Persistent coxsackievirus B infection and pathogenesis of type 1 diabetes mellitus[J]. Nat Rev Endocrinol, 2022, 18: 503-516. doi: 10.1038/s41574-022-00688-1 [17] Carré A, Vecchio F, Flodström-Tullberg M, et al. Coxsackievirus and Type 1 Diabetes: Diabetogenic Mechanisms and Implications for Prevention[J]. Endocr Rev, 2023, 44: 737-751. doi: 10.1210/endrev/bnad007 [18] Root-Bernstein R, Chiles K, Huber J, et al. Clostridia and Enteroviruses as Synergistic Triggers of Type 1 Diabetes Mellitus[J]. Int J Mol Sci, 2023, 24: 8336. doi: 10.3390/ijms24098336 [19] Prince MI, Ducker SJ, James OF. Case-control studies of risk factors for primary biliary cirrhosis in two United Kingdom populations[J]. Gut, 2010, 59: 508-512. doi: 10.1136/gut.2009.184218 [20] Tanaka A, Leung PSC, Gershwin ME. Pathogen infections and primary biliary cholangitis[J]. Clin Exp Immunol, 2019, 195: 25-34. [21] Bjornevik K, Cortese M, Healy BC, et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis[J]. Science, 2022, 375: 296-301. doi: 10.1126/science.abj8222 [22] Robinson WH, Steinman L. Epstein-Barr virus and multiple sclerosis[J]. Science, 2022, 375: 264-265. doi: 10.1126/science.abm7930 [23] He R, Du Y, Wang C. Epstein-Barr virus infection: the leading cause of multiple sclerosis[J]. Signal Transduct Target Ther, 2022, 7: 239. doi: 10.1038/s41392-022-01100-0 [24] Rostgaard K, Nielsen NM, Melbye M, et al. Siblings reduce multiple sclerosis risk by preventing delayed primary Epstein-Barr virus infection[J]. Brain, 2023, 146: 1993-2002. doi: 10.1093/brain/awac401 [25] Afrasiabi A, Keane JT, Ong LTC, et al. Genetic and transcriptomic analyses support a switch to lytic phase in Epstein Barr virus infection as an important driver in developing Systemic Lupus Erythematosus[J]. J Autoimmun, 2022, 127: 102781. doi: 10.1016/j.jaut.2021.102781 [26] Harley JB, James JA. Epstein-Barr virus infection induces lupus autoimmunity[J]. Bull NYU Hosp Jt Dis, 2006, 64: 45-50. [27] Reis AD, Mudinutti C, de Freitas Peigo M, et al. Active human herpesvirus infections in adults with systemic lupus erythematosus and correlation with the SLEDAI score[J]. Adv Rheumatol, 2020, 60: 42. doi: 10.1186/s42358-020-00144-6 [28] Mahroum N, Elsalti A, Shoenfeld Y. Herpes simplex virus and SLE: Though uncommon yet with significant implications[J]. J Med Virol, 2023, 95: e28689. doi: 10.1002/jmv.28689 [29] Tomofuji Y, Maeda Y, Oguro-Igashira E, et al. Metagenome- wide association study revealed disease-specific landscape of the gut microbiome of systemic lupus erythematosus in Japanese[J]. Ann Rheum Dis, 2021, 80: 1575-1583. doi: 10.1136/annrheumdis-2021-220687 [30] Aletaha D, Smolen JS. Diagnosis and Management of Rheumatoid Arthritis: A Review[J]. JAMA, 2018, 320: 1360-1372. doi: 10.1001/jama.2018.13103 [31] Maeda Y, Kurakawa T, Umemoto E, et al. Dysbiosis Contributes to Arthritis Development via Activation of Autoreac-tive T Cells in the Intestine[J]. Arthritis Rheumatol, 2016, 68: 2646-2661. doi: 10.1002/art.39783 [32] Wegner N, Wait R, Sroka A, et al. Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and α-enolase: implications for autoimmunity in rheumatoid arthritis[J]. Arthritis Rheum, 2010, 62: 2662-2672. doi: 10.1002/art.27552 [33] Jiang L, Shang M, Yu S, et al. A high-fiber diet synergizes with Prevotella copri and exacerbates rheumatoid arthritis[J]. Cell Mol Immunol, 2022, 19: 1414-1424. doi: 10.1038/s41423-022-00934-6 [34] Zheng Z, Sohn S, Ahn KJ, et al. Serum reactivity against herpes simplex virus type 1 UL48 protein in Behçet's disease patients and a Behçet's disease-like mouse model[J]. Acta Derm Venereol, 2015, 95: 952-958. doi: 10.2340/00015555-2127 [35] Silva NSM, Rodrigues LFC, Dores-Silva PR, et al. Structural, thermodynamic and functional studies of human 71 kDa heat shock cognate protein (HSPA8/hHsc70)[J]. Biochim Biophys Acta Proteins Proteom, 2021, 1869: 140719. doi: 10.1016/j.bbapap.2021.140719 [36] Yang TH, Aosai F, Norose K, et al. Heat shock cognate protein 71-associated peptides function as an epitope for Toxoplasma gondii-specific CD4+CTL[J]. Microbiol Immunol, 1997, 41: 553-561. doi: 10.1111/j.1348-0421.1997.tb01891.x [37] Cho SB, Zheng Z, Ahn KJ, et al. Serum IgA reactivity against GroEL of Streptococcus sanguinis and human heterogeneous nuclear ribonucleoprotein A2/B1 in patients with Behçet disease[J]. Br J Dermatol, 2013, 168: 977-983. doi: 10.1111/bjd.12128 [38] Deniz R, Emrence Z, Yalçinkaya Y, et al. Improved sensitivity of the skin pathergy test with polysaccharide pneumococcal vaccine antigens in the diagnosis of Behçet disease[J]. Rheumatology (Oxford), 2023, 62: 1903-1909. doi: 10.1093/rheumatology/keac543 [39] Ouchene L, Muntyanu A, Lavoué J, et al. Toward Understanding of Environmental Risk Factors in Systemic Sclerosis[J]. J Cutan Med Surg, 2021, 25: 188-204. doi: 10.1177/1203475420957950 [40] Soffritti I, D'Accolti M, Maccari C, et al. Human Cytomegalovirus and Human Herpesvirus 6 Coinfection of Dermal Fibroblasts Enhances the Pro-Inflammatory Pathway Predisposing to Fibrosis: The Possible Impact on Systemic Sclerosis[J]. Microorganisms, 2022, 10: 1600. doi: 10.3390/microorganisms10081600 [41] Arvia R, Zakrzewska K, Giovannelli L, et al. Parvovirus B19 induces cellular senescence in human dermal fibroblasts: putative role in systemic sclerosis-associated fibrosis[J]. Rheumatology (Oxford), 2022, 61: 3864-3874. doi: 10.1093/rheumatology/keab904 [42] Kim S, Park HJ, Lee SI. The Microbiome in Systemic Sclerosis: Pathophysiology and Therapeutic Potential[J]. Int J Mol Sci, 2022, 23: 16154. doi: 10.3390/ijms232416154 [43] Stec A, Maciejewska M, Paralusz-Stec K, et al. The Gut Microbial Metabolite Trimethylamine N-Oxide is Linked to Specific Complications of Systemic Sclerosis[J]. J Inflamm Res, 2023, 16: 1895-1904. doi: 10.2147/JIR.S409489 [44] Mofors J, Arkema EV, Björk A, et al. Infections increase the risk of developing Sjögren's syndrome[J]. J Intern Med, 2019, 285: 670-680. doi: 10.1111/joim.12888 [45] Croia C, Astorri E, Murray-Brown W, et al. Implication of Epstein-Barr virus infection in disease-specific autoreactive B cell activation in ectopic lymphoid structures of Sjögren's syndrome[J]. Arthritis Rheumatol, 2014, 66: 2545-2557. doi: 10.1002/art.38726 [46] Iwakiri D, Zhou L, Samanta M, et al. Epstein-Barr virus (EBV)-encoded small RNA is released from EBV-infected cells and activates signaling from Toll-like receptor 3[J]. J Exp Med, 2009, 206: 2091-2099. doi: 10.1084/jem.20081761 [47] de Paiva CS, Jones DB, Stern ME, et al. Altered Mucosal Microbiome Diversity and Disease Severity in Sjögren Syndrome[J]. Sci Rep, 2016, 6: 23561. doi: 10.1038/srep23561 [48] Liu Y, Sawalha AH, Lu Q. COVID-19 and autoimmune diseases[J]. Curr Opin Rheumatol, 2021, 33: 155-162. doi: 10.1097/BOR.0000000000000776 [49] Zhang Y, Xiao M, Zhang S, et al. Coagulopathy and Antiphospholipid Antibodies in Patients with COVID-19[J]. N Engl J Med, 2020, 382: e38. doi: 10.1056/NEJMc2007575 [50] Xiao M, Zhang Y, Zhang S, et al. Antiphospholipid Antibodies in Critically Ill Patients With COVID-19[J]. Arthritis Rheumatol, 2020, 72: 1998-2004. doi: 10.1002/art.41425 [51] Wang G, Wang Q, Wang Y, et al. Presence of Anti-MDA5 Antibody and Its Value for the Clinical Assessment in Patients With COVID-19: A Retrospective Cohort Study[J]. Front Immunol, 2021, 12: 791348. doi: 10.3389/fimmu.2021.791348 [52] Philippot Q, Fekkar A, Gervais A, et al. Autoantibodies Neutralizing Type I IFNs in the Bronchoalveolar Lavage of at Least 10% of Patients During Life-Threatening COVID-19 Pneumonia[J]. J Clin Immunol, 2023, 43: 1093-1103. [53] Solanich X, Rigo-Bonnin R, Gumucio VD, et al. Pre-existing Autoantibodies Neutralizing High Concentrations of Type I Interferons in Almost 10% of COVID-19 Patients Admitted to Intensive Care in Barcelona[J]. J Clin Immunol, 2021, 41: 1733-1744. [54] Barrett CE, Koyama AK, Alvarez P, et al. Risk for Newly Diagnosed Diabetes >30 Days After SARS-CoV-2 Infection Among Persons Aged < 18 Years- United States, March 1, 2020-June 28, 2021[J]. MMWR Morb Mortal Wkly Rep, 2022, 71: 59-65. [55] McKeigue PM, McGurnaghan S, Blackbourn L, et al. Relation of Incident Type 1 Diabetes to Recent COVID-19 Infection: Cohort Study Using e-Health Record Linkage in Scotland[J]. Diabetes Care, 2023, 46: 921-928. [56] Daly JL, Simonetti B, Klein K, et al. Neuropilin-1 is a host factor for SARS-CoV-2 infection[J]. Science, 2020, 370: 861-865. [57] Cantuti-Castelvetri L, Ojha R, Pedro LD, et al. Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity[J]. Science, 2020, 370: 856-860. [58] Wu CT, Lidsky PV, Xiao Y, et al. SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment[J]. Cell Metab, 2021, 33: 1565-1576. e5. [59] Chen J, Wu C, Wang X, et al. The Impact of COVID-19 on Blood Glucose: A Systematic Review and Meta-Analysis[J]. Front Endocrinol (Lausanne), 2020, 11: 574541. [60] Bonometti R, Sacchi MC, Stobbione P, et al. The first case of systemic lupus erythematosus (SLE) triggered by COVID-19 infection[J]. Eur Rev Med Pharmacol Sci, 2020, 24: 9695-9697. [61] Valencia Sanchez C, Theel E, Binnicker M, et al. Autoimmune Encephalitis After SARS-CoV-2 Infection: Case Frequency, Findings, and Outcomes[J]. Neurology, 2021, 97: e2262-e2268. [62] Capes A, Bailly S, Hantson P, et al. COVID-19 infection associated with autoimmune hemolytic anemia[J]. Ann Hematol, 2020, 99: 1679-1680. [63] Bourgonje AR, Andreu-Sánchez S, Vogl T, et al. Phage-display immunoprecipitation sequencing of the antibody epitope repertoire in inflammatory bowel disease reveals distinct antibody signatures[J]. Immunity, 2023, 56: 1393-1409. e6. [64] Enose-Akahata Y, Wang L, Almsned F, et al. The repertoire of CSF antiviral antibodies in patients with neuroinflammatory diseases[J]. Sci Adv, 2023, 9: eabq6978. -
点击查看大图
表(1)
计量
- 文章访问数: 1358
- HTML全文浏览量: 39
- PDF下载量: 195
- 被引次数: 0
