IGG4-MEDIATED AORTIC ANEURYSM: PATHOGENESIS AND THERAPEUTIC STRATEGY
DOI:
https://doi.org/10.56238/arev8n2-066Keywords:
Aneurysm, Aortic Aneurysm, Abdominal Aorta, Immunoglobulin G4-Related DiseaseAbstract
Abdominal aortic aneurysm (AAA) is a multifactorial chronic inflammatory condition associated with a high risk of mortality, especially in cases of rupture. IgG4-related disease (IgG4-RD) has been implicated in the pathogenesis of aortic aneurysms, particularly in cases of aortitis and periaortitis, where there is tissue infiltration by IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. This study conducted an integrative literature review, with research performed in PubMed using descriptors related to IgG4 and abdominal aortic aneurysm. The results indicate that IgG4-RD affects large vessels, such as the aorta, and may lead to the development of inflammatory aneurysms, particularly in the infra-abdominal region. The pathogenesis includes inflammation mediated by innate and adaptive immune cells, complement system activation, angiogenesis, the action of cytokines such as IL-6 and APRIL, and the formation of tertiary lymphoid tissues in the adventitial layer. The presence of perivascular adipocytes also contributes to the chronic inflammatory process. Treatment is based on glucocorticoids, effective in inducing remission, but associated with adverse effects. In refractory cases, immunosuppressants or biological therapies, such as anti-CD20 antibodies, are used. Understanding the role of IgG4 in the pathogenesis of AAA allows for greater diagnostic precision and can favor personalized therapeutic approaches, contributing to the prevention of complications such as aneurysmal rupture. The need for multidisciplinary clinical attention and continuous professional updating in the face of this complex and potentially fatal condition is highlighted.
Downloads
References
ALEMANY, V. S., FORTIER, J., GUPTA, H., et al. A rare case of IgG4-related aortitis in the thoracic aorta mimicking an intramural hematoma: navigating the diagnostic labyrinth. Journal of Cardiothoracic Surgery, v. 19, n. 1, p. 599, 2024. doi: 10.1186/s13019-024-03026-w DOI: https://doi.org/10.1186/s13019-024-03026-w
DESHPANDE, V., ZEN, Y., CHAN, J. K., et al. Consensus statement on the pathology of IgG4-related disease. Modern Pathology, v. 25, n. 9, p. 1181-92, 2012. doi: 10.1038/modpathol.2012.72 DOI: https://doi.org/10.1038/modpathol.2012.72
ITO, E., OHKI, T., KASA, K., et al. Clinicopathological analysis of enlarged abdominal aortic aneurysms after endovascular aneurysm repair and the relationship with occult IgG4-related vascular disease. Surgery Today, v. 55, n. 6, p. 839-846, 2025. doi: 10.1007/s00595-024-02966-z DOI: https://doi.org/10.1007/s00595-024-02966-z
KASASHIMA, F., KAWAKAMI, K., MATSUMOTO, Y., et al. IgG4-Related Arterial Disease. Annals of Vascular Diseases, v. 11, n. 1, p. 72-77, 2018a. doi: 10.3400/avd.ra.18-00012 DOI: https://doi.org/10.3400/avd.ra.18-00012
KASASHIMA, S., KAWASHIMA, A., KASASHIMA, F., et al protein, in IgG4-related vascular diseases. Heart and Vessels, v. 33, n. 12, p.1471-1481, 2018b.doi: 10.1007/s00380-018-1203-8 DOI: https://doi.org/10.1007/s00380-018-1203-8
KASASHIMA, S., ZEN, Y. IgG4-related inflammatory abdominal aortic aneurysm. Current Opinion in Rheumatology, v. 23, n. 1, p. 18-23, 2011. doi: 10.1097/BOR.0b013e32833ee95f DOI: https://doi.org/10.1097/BOR.0b013e32833ee95f
KAWAKAMI, T., MIZUSHIMA, I., YAMADA, K., et al. Abundant a proliferation-inducing ligand (APRIL)-producing macrophages contribute to plasma cell accumulation in immunoglobulin G4-related disease. Nephrology Dialysis Transplantation, v. 34, n. 6, p. 960-969, 2019.doi: 10.1093/ndt/gfy296 DOI: https://doi.org/10.1093/ndt/gfy296
KESSLER, V., KLOPF, J., EILENBERG, W., et al. AAA Revisited: A Comprehensive Review of Risk Factors, Management, and Hallmarks of Pathogenesis. Biomedicines, v. 10, n. 1, p. 94, 2022.doi: 10.3390/biomedicines10010094 DOI: https://doi.org/10.3390/biomedicines10010094
KHAN, M. A., ULLAH, N., KHAN, S., et al. Navigating the Diagnostic Maze: A Case Report of Immunoglobulin G4-Related Disease. Cureus, v. 16, n. 7, p. e64502, 2024.doi: 10.7759/cureus.64502 DOI: https://doi.org/10.7759/cureus.64502
KLOTZKA, A., MARIOWSKA, A., BŁASZYK, M., LESIAK, M. Cardiac tumor and aortic aneurysm as initial manifestations of IgG4-related disease. Polish Heart Journal (Kardiologia Polska), v. 83, n. 11, p. 1353-1354, 2025.doi: 10.33963/v.phj.108284 DOI: https://doi.org/10.33963/v.phj.108284
LAI, K. K. H., ANG, T. W. X., CHEUK, W., et al. Advances in understanding and management of IgG4-related ophthalmic disease. Asia-Pacific journal of ophthalmology (Philadelphia, Pa.), v. 13, n. 5, p. 100101, 2024.doi: 10.1016/j.apjo.2024.100101 DOI: https://doi.org/10.1016/j.apjo.2024.100101
LEE, C., TO, C. H. IgG4-Related Disease: A Concise Review. Journal of Clinical Rheumatology and Immunology, v. 23, n. 1, p. 25-34, 2023. doi: https://doi.org/10.1142/S2661341723300033 DOI: https://doi.org/10.1142/S2661341723300033
LIU, Y., ZENG, Q., ZHU, L., et al. Relapse predictors and serologically unstable condition of IgG4-related disease: a large Chinese cohort. Rheumatology (Oxford), v. 59, n. 8, p. 2115-2123, 2020. doi: 10.1093/rheumatology/kez669 DOI: https://doi.org/10.1093/rheumatology/kez669
MATHEW, A., RAKESH, N. R., KAUSHAL, G., et al. IgG4-Related Pancreato-Biliary Disease in the Disguise of Malignancy. The American Surgeon, v. 89, n. 6, p. 2985-2988, 2023. doi: 10.1177/00031348221102610 DOI: https://doi.org/10.1177/00031348221102610
MENDES, K. D. S.; SILVEIRA, R. C. DE C. P.; GALVÃO, C. M. Revisão integrativa: método de pesquisa para a incorporação de evidências na saúde e na enfermagem. Texto & Contexto - Enfermagem, v. 17, n. 4, p. 758–764, 2008. doi: https://doi.org/10.1590/S0104-07072008000400018 DOI: https://doi.org/10.1590/S0104-07072008000400018
MIZUSHIMA, I., KASASHIMA, S., YAMADA, K., et al. THU0382 Involvement of Macrophages and A Proliferation-Inducing Ligand (APRIL) in Igg4-Related Inflammatory Abdominal Aortic Aneurysm. Annals of the Rheumatic Diseases, v. 73, Supp 2, p. 314, 2014. doi: https://doi.org/10.1136/annrheumdis-2014-eular.2803 DOI: https://doi.org/10.1136/annrheumdis-2014-eular.2803
MIZUSHIMA, I., KONISHI, M., SANADA, H., et al. Serum IgG4 levels at diagnosis can predict unfavorable outcomes of untreated patients with IgG4-related disease. Scientific Reports, v. 11, n, 1, p. 13341, 2021. doi: 10.1038/s41598-021-92814-8 DOI: https://doi.org/10.1038/s41598-021-92814-8
MIZUSHIMA, I., MORIKAGE, N., ITO, E., et al. Validation of the Diagnostic Criteria for IgG4-Related Periaortitis/Periarteritis and Retroperitoneal Fibrosis (IgG4PA/RPF) 2018, and Proposal of a Revised 2023 Version for IgG4-Related Cardiovascular/Retroperitoneal Disease. Circulation Journal, v. 88, n. 10, p. 1679-1688, 2024. doi: 10.1253/circj.CJ-24-0026 DOI: https://doi.org/10.1136/annrheumdis-2024-eular.1148
NACKENHORST, M. C., KAPALLA, M., WEIDLE, S., et al. The Incidence of IgG4-Related and Inflammatory Abdominal Aortic Aneurysm Is Rare in a 101 Patient Cohort. Journal of Clinical Medicine, v. 12, n. 12, p. 4029, 2023. doi: 10.3390/jcm12124029 DOI: https://doi.org/10.3390/jcm12124029
NAKAYAMADA, S., TANAKA, Y. Development of targeted therapies in IgG4-related disease. Modern Rheumatology, v. 33, n. 2, p. 266-270, 2023. doi: 10.1093/mr/roac096 DOI: https://doi.org/10.1093/mr/roac096
NIKIPHOROU, E., GALLOWAY, J., FRAGOULIS, G. E. Overview of IgG4-related aortitis and periaortitis. A decade since their first description. Autoimmunity Reviews, v. 19, n. 12, p. 102694, 2020. doi: 10.1016/j.autrev.2020.102694 DOI: https://doi.org/10.1016/j.autrev.2020.102694
OYAMA-MANABE, N., MANABE, O., TSUNETA, S. RadioGraphics Update: IgG4-related Cardiovascular Disease from the Aorta to the Coronary Arteries. Radiographics, v. 40, n. 7, p. E29-E32, 2020. doi: 10.1148/rg.2020190219 DOI: https://doi.org/10.1148/rg.2020190219
PÉREZ-GARCÍA, C. N., OLMOS, C., VIVAS, D., et al. IgG4-aortitis among thoracic aortic aneurysms. Heart. 2019 Oct;105(20):1583-1589. doi: 10.1136/heartjnl-2018-314499. DOI: https://doi.org/10.1136/heartjnl-2018-314499
PRADHAN-NABZDYK, L., HUANG, C., LOGERFO, F. W., NABZDYK, C. S. Current siRNA targets in atherosclerosis and aortic aneurysm. Discovery medicine, v. 17, n. 95, p. 233-246, 2014.
PRUCHA, M., SEDIVY, P., STADLER, P., et al. Abdominal aortic aneurysm as an IgG4-related disease. Clinical and Experimental Immunology, v. 197, n. 3, p. 361–365, 2019. doi: 10.1111/cei.13307. DOI: https://doi.org/10.1111/cei.13307
SEDHOM, R., SEDHOM, D., STRAIR, R. IgG-4 related disease: A mini-review. Journal of Rare Diseases Research & Treatment, v. 2, n. 2, p. 18-23, 2017. doi: 10.29245/2572-9411/2017/2.1089 DOI: https://doi.org/10.29245/2572-9411/2017/2.1089
SHIZUKU, T., YAMAGUCHI, H. Aortoduodenal Fistula With IgG4-Related Periaortitis: A Case Report. Cureus, v. 16, n. 11, p. e73193, 2024. doi: 10.7759/cureus.73193 DOI: https://doi.org/10.7759/cureus.73193
SOH, B. W. T., PRENDERGAST, S. C., BURKE, L., et al. Severe Aortic Valvular Incompetence From IgG4-Related Disease: An Unusual Entity. JACC: Case Reports, v. 24, p. 102027, 2023. doi: 10.1016/j.jaccas.2023.102027 DOI: https://doi.org/10.1016/j.jaccas.2023.102027
SOUBRIER, M., HACHULLA, E. IgG4-Related Arterial Disease: An Unusual Case of Aortitis. Journal of Rheumatology, v. 52, n. 6, p. 618-619, 2025. doi: 10.3899/jrheum.2024-0888 DOI: https://doi.org/10.3899/jrheum.2024-0888
SPEAR, R., BOYTARD, L., BLERVAQUE, R., et al. Adventitial Tertiary Lymphoid Organs as Potential Source of MicroRNA Biomarkers for Abdominal Aortic Aneurysm. International Journal of Molecular Sciences, v. 16, n. 5, p. 11276-11293, 2015. doi: https://doi.org/10.3390/ijms160511276 DOI: https://doi.org/10.3390/ijms160511276
SUEHIRO, Y., SEO, H., SUEHIRO, S., HIRAI, H. Surgical strategy of IgG4-related inflammatory abdominal aortic aneurysm with preoperative steroid therapy: A case report. Annals of Vascular Surgery, v. 77, n. 351, p. e1-351.e6, 2021. doi: 10.1016/j.avsg.2021.05.041 DOI: https://doi.org/10.1016/j.avsg.2021.05.041
TAGUCHI, T., NISHI, H., KITAHARA, M., et al. Surgical Treatment for Giant Multiple Coronary Artery Aneurysms Caused by an IgG4-Related Disease. Cureus, v. 16, n. 5, p. e60115, 2024. doi: 10.7759/cureus.60115 DOI: https://doi.org/10.7759/cureus.60115
TRIBOVANE, D., MONTILVA, S. S. Neuro-ophthalmologic IgG4-related disease: a case report. Open Journal of Clinical and Medical Case Reports, v. 11, n. 1, p. 1095, 2024. doi: https://doi.org/10.47739/2333-6447/1095
TYAGI, S., SAFAL, S., TYAGI, D. Aortitis and aortic aneurysm in systemic vasculitis. Indian Journal of Thoracic and Cardiovascular Surgery, v. 35, Suppl 2, p. 47-56, 2019. doi: 10.1007/s12055-019-00832-z DOI: https://doi.org/10.1007/s12055-019-00832-z
UMEHARA, H., OKAZAKI, K., MASAKI, Y., et al. A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details. Modern Rheumatology, v. 22, n. 1, p. 1-14, 2012. doi: 10.1007/s10165-011-0508-6 DOI: https://doi.org/10.3109/s10165-011-0508-6
WALLACE, Z. S., MILES, G., SMOLKINA, E., et al. Incidence, prevalence and mortality of IgG4-related disease in the USA: a claims-based analysis of commercially insured adults. Annals of the Rheumatic Diseases, v. 82, n. 7, p. 957-962, 2023. doi: 10.1136/ard-2023-223950 DOI: https://doi.org/10.1136/ard-2023-223950
YOSHIKAI, M., SATO, H., KUWANO, A., NISHIDA, N. Common Femoral Artery Aneurysm: A Rare Manifestation of Immunoglobulin G4-Related Disease. Annals of Vascular Diseases, v. 18, n. 1, p. 25-00014, 2025. doi: 10.3400/avd.cr.25-00014 DOI: https://doi.org/10.3400/avd.cr.25-00014
ZHANG, X., WU, G., WANG, M., et al. Novel Advances in the Study of IgG4-Related Disease in the Eye and Ocular Adnexa. Ophthalmic Research, v. 65, n. 6, p. 605-614, 2022. doi: 10.1159/000525955 DOI: https://doi.org/10.1159/000525955
