{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:54:27Z","timestamp":1790747667388,"version":"4.1.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Thromboembolism is a critical complication of severe\n                      <jats:italic>Mycoplasma pneumoniae<\/jats:italic>\n                      pneumonia (SMPP) in children, yet its clinical spectrum and immunothrombotic mechanisms remain poorly defined. The \u201cdual-hit\u201d hypothesis\u2014synergy between infection-induced inflammation and transient antiphospholipid antibodies (aPLs)\u2014lacks integrated clinical validation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We report a case of extensive multi-system thrombosis in a 6-year-old boy with SMPP. A systematic review of literature (January 2020\u2013December 2025) identified 19 studies comprising 199 pediatric cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the index case, thrombosis coincided with hyperinflammation and transient aPLs, which seroconverted to negative upon recovery. Pooled analysis showed multi-system involvement in 27.1% of cases (54\/199). Among tested patients (n = 65; 32.7% of the cohort), aPL positivity was 69.2% (45\/65). Most patients achieved favorable outcomes with anticoagulation and immunomodulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study is consistent with the \u201cdual-hit\u201d model in SMPP, where systemic inflammation may prime the endothelium and transient aPL positivity coincides with an extensive thrombotic burden. The high prevalence of multi-system involvement supports low-threshold vascular imaging and aPLs screening, along with biomarker-guided management. Transient aPLs should be interpreted as a potential risk-amplifying biomarker rather than a proven causal driver of thrombosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1845246","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:54:41Z","timestamp":1790744081000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pentasystem embolism associated with transient antiphospholipid antibodies in severe M. pneumoniae pneumonia: a \u201cDual-Hit\u201d case report and systematic review"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuhang","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Pediatric Critical Care Medicine, Sichuan Provincial Maternity and Child Health Care Hospital","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Critical Care Medicine, Sichuan Provincial Maternity and Child Health Care Hospital","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Critical Care Medicine, Sichuan Provincial Maternity and Child Health Care Hospital","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Critical Care Medicine, Sichuan Provincial Maternity and Child Health Care Hospital","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Critical Care Medicine, Sichuan Provincial Maternity and Child Health Care Hospital","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pediatric Critical Care Medicine, Sichuan Provincial Maternity and Child Health Care Hospital","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Radiology, Sichuan Provincial Maternity and Child Health Care Hospital","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianmin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Critical Care Medicine, Sichuan Provincial Maternity and Child Health Care Hospital","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s12519-024-00831-0","article-title":"Expert consensus on the diagnosis and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children","volume":"20","author":"Wang","year":"2024","journal-title":"World J Pediatr"},{"key":"B2","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1186\/s13052-022-01344-0","article-title":"Analysis of the risk factors and clinical features of Mycoplasma pneumoniae pneumonia with embolism in children: a retrospective study","volume":"48","author":"Han","year":"2022","journal-title":"Ital J Pediatr"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.1673-4408.2019.02.008","article-title":"\u513f\u7ae5\u80ba\u708e\u652f\u539f\u4f53\u80ba\u708e\u5408\u5e76\u8840\u6db2\u9ad8\u51dd\u72b6\u6001\u7684\u7814\u7a76\u8fdb\u5c55 [Mycoplasma pneumoniae combined with thrombophilia in children","volume":"46","author":"Li","year":"2019","journal-title":"Int J Pediatr"},{"key":"B4","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1128\/CMR.17.4.697-728.2004","article-title":"Mycoplasma pneumoniae and its role as a human pathogen","volume":"17","author":"Waites","year":"2004","journal-title":"Clin Microbiol Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1674-3806.2025.08.05","article-title":"\u513f\u7ae5\u80ba\u708e\u652f\u539f\u4f53\u80ba\u708e\u5408\u5e76\u80ba\u52a8\u8109\u6813\u585e11\u4f8b\u4e34\u5e8a\u7279\u5f81\u5206\u6790 [Analysis on clinical features of 11 cases of Mycoplasma pneumoniae pneumonia complicated with pulmonary embolism in children","volume":"18","author":"Fan","year":"2025","journal-title":"Chin J New Clin Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/crj.13584","article-title":"Thromboembolic complications of Mycoplasma pneumoniae pneumonia in children","volume":"17","author":"Chen","year":"2023","journal-title":"Clin Respir J"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S459626","article-title":"Characteristics and outcomes of Mycoplasma pneumoniae pneumonia associated with pulmonary embolism and necrotizing pneumonia in children","volume":"17","author":"Wang","year":"2024","journal-title":"Infect Drug Resist"},{"key":"B8","doi-asserted-by":"publisher","first-page":"96","DOI":"10.6040\/j.issn.1671-7554.0.2023.0377","article-title":"\u513f\u7ae5\u80ba\u708e\u652f\u539f\u4f53\u80ba\u708e\u5408\u5e76\u80ba\u6813\u585e9\u4f8b\u4e34\u5e8a\u5206\u6790\u5e76\u6587\u732e\u590d\u4e60 [Clinical analysis of 9 cases of Mycoplasma pneumoniae pneumonia complicated with pulmonary embolism in children and literature review","volume":"61","author":"Song","year":"2023","journal-title":"J Shandong Univ (Health Sci)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.13609\/j.cnki.1000-0313.2021.05.015","article-title":"CTA\u5728\u513f\u7ae5\u91cd\u75c7\u652f\u539f\u4f53\u80ba\u708e\u5408\u5e76\u8840\u7ba1\u6813\u585e\u4e2d\u7684\u8bca\u65ad\u4ef7\u503c [Diagnostic value of CTA in children with severe Mycoplasma pneumoniae pneumonia complicated with vascular embolism","volume":"36","author":"Wang","year":"2021","journal-title":"Radiol Pract"},{"key":"B10","doi-asserted-by":"publisher","first-page":"201","DOI":"10.3892\/etm.2021.9634","article-title":"Mycoplasma pneumoniae pneumonia with pulmonary embolism: a study on pediatric cases in Jilin province of China","volume":"21","author":"Sheng","year":"2021","journal-title":"Exp Ther Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000046541","article-title":"Was the occurrence of Mycoplasma pneumoniae pneumonia combined with cerebral watershed infarction a coincidence?: a CARE compliant case series and literature review","volume":"104","author":"Wang","year":"2025","journal-title":"Medicine"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1002-0152.2024.02.007","article-title":"\u513f\u7ae5\u91cd\u75c7\u80ba\u708e\u652f\u539f\u4f53\u80ba\u708e\u81f4\u4e0d\u540c\u7c7b\u578b\u8111\u6897\u6b7b3\u4f8b [Different types of cerebral infarction caused by severe Mycoplasma pneumoniae pneumonia in 3 children","volume":"50","author":"Wang","year":"2024","journal-title":"Chin J Nerv Ment Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn112140-20250221-00137","article-title":"\u513f\u7ae5\u91cd\u75c7\u80ba\u708e\u652f\u539f\u4f53\u80ba\u708e\u5e76\u53d1\u5fc3\u8154\u5185\u8840\u681315\u4f8b\u4e34\u5e8a\u5206\u6790 [Clinical analysis of 15 cases of severe Mycoplasma pneumoniae pneumonia complicated by cardiac thrombosis in children","volume":"63","author":"Yang","year":"2025","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1000-3606.2021.06.005","article-title":"\u80ba\u708e\u652f\u539f\u4f53\u80ba\u708e\u5e76\u53d1\u5fc3\u8154\u5185\u8840\u6813\u3001\u80ba\u6813\u585e1\u4f8b\u5e76\u6587\u732e\u590d\u4e60 [Mycoplasma pneumoniae pneumonia complicated with cardiac thrombus and pulmonary embolism: a case report and literature review","volume":"39","author":"Huang","year":"2021","journal-title":"Int J Pediatr"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000024297","article-title":"Cardiac thrombus and stroke in a child with Mycoplasma pneumoniae pneumonia: a case report","volume":"100","author":"Wang","year":"2021","journal-title":"Medicine"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1186\/s12879-025-11481-6","article-title":"Intestinal necrosis due to nonocclusive mesenteric ischemia in a child with Mycoplasma pneumoniae pneumonia: a case report","volume":"25","author":"Li","year":"2025","journal-title":"BMC Infect Dis"},{"key":"B17","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1186\/s12887-021-02845-3","article-title":"Multiple anatomic sites of infarction in a pediatric patient with M. pneumoniae infection, a case report","volume":"21","author":"Hahn","year":"2021","journal-title":"BMC Pediatr"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.1673-4408.2022.04.013","article-title":"\u513f\u7ae5\u80ba\u708e\u652f\u539f\u4f53\u80ba\u708e\u76f8\u5173\u9ad8\u51dd\u72b6\u6001\u53ca\u708e\u75c7\u6307\u6807\u7684\u4e34\u5e8a\u7814\u7a76\u8fdb\u5c55 [Progress on Mycoplasma pneumoniae pneumonia related hypercoagulable state and inflammation indicators in children","volume":"49","author":"Yang","year":"2022","journal-title":"Int J Pediatr"},{"key":"B19","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1186\/s12887-023-04188-7","article-title":"A retrospective study of the clinical characteristics of 9 children with pulmonary embolism associated with Mycoplasma pneumoniae pneumonia","volume":"23","author":"Song","year":"2023","journal-title":"BMC Pediatr"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/8708417","article-title":"Deep vein thrombosis and pulmonary embolism in the setting of Mycoplasma infection","volume":"2020","author":"Saleem","year":"2020","journal-title":"Case Rep Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.29063\/ajrh2024\/v28i11.20","article-title":"Severe Mycoplasma pneumoniae pneumonia combined with cold agglutinin disease and pulmonary embolism in childhood: a case report and review of the literature","volume":"28","author":"Liang","year":"2024","journal-title":"Afr J Reprod Health"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.26691","article-title":"Pulmonary embolism associated with Mycoplasma pneumoniae pneumonia in children","volume":"58","author":"Chen","year":"2023","journal-title":"Pediatr Pulmonol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1186\/s12887-024-05283-z","article-title":"Pulmonary thromboembolism due to Mycoplasma pneumoniae in children: a case report and literature review","volume":"24","author":"Cheng","year":"2024","journal-title":"BMC Pediatr"},{"key":"B24","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s13052-024-01690-1","article-title":"Mycoplasma pneumoniae pneumonia-associated thromboembolism with plastic bronchitis: a series of five case reports and literature review","volume":"50","author":"Jin","year":"2024","journal-title":"Ital J Pediatr"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2025.1449493","article-title":"Successful rivaroxaban and doxycycline therapy for Mycoplasma pneumonia with pulmonary embolism in children: a case report","volume":"13","author":"Xiaoqian","year":"2025","journal-title":"Front Pediatr"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.7499\/j.issn.1008-8830.2311146","article-title":"\u96be\u6cbb\u6027\u80ba\u708e\u652f\u539f\u4f53\u80ba\u708e\u60a3\u513f\u5408\u5e76\u6813\u585e\u7684\u5371\u9669\u56e0\u7d20\u5206\u6790\u53ca\u5217\u7ebf\u56fe\u9884\u6d4b\u6a21\u578b\u7684\u6784\u5efa [Risk factors for embolism in children with refractory Mycoplasma pneumoniae pneumonia and construction of a nomogram model for prediction of embolism","volume":"26","author":"Xie","year":"2024","journal-title":"Zhongguo Dang Dai Er Ke Za Zhi"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2025.1608233","article-title":"Case report: refractory Mycoplasma pneumoniae pneumonia complicated by pulmonary embolism and infarction in a child","volume":"13","author":"Zhang","year":"2025","journal-title":"Front Pediatr"},{"key":"B28","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s12959-025-00748-2","article-title":"Interventional therapy for a case of Mycoplasma pneumoniae pneumonia complicated by upper extremity arterial embolism in a child: a case report","volume":"23","author":"Zhang","year":"2025","journal-title":"Thromb J"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1016\/S1473-3099(20)30253-X","article-title":"Pulmonary embolism associated with mycoplasma in a child","volume":"20","author":"Chen","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3181c98d21","article-title":"Inflammation and coagulation","volume":"38","author":"Levi","year":"2010","journal-title":"Crit Care Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1046\/j.1538-7836.2003.00261.x","article-title":"Inflammation and thrombosis","volume":"1","author":"Esmon","year":"2003","journal-title":"J Thromb Haemost"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2026.03.024","article-title":"Inhalable PD-L1-engineered hybrid cellular vesicles suppress excessive neutrophil activation and restore mitochondrial homeostasis to alleviate ischemia\u2013reperfusion lung injury and pneumonia","volume":"62","author":"Yuan","year":"2026","journal-title":"Bioact Mater"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-021-05724-5","article-title":"Are antiphospholipid antibodies just a common epiphenomenon or are they causative of immune-mediated coagulopathy in COVID-19","volume":"40","author":"Castillo-Mart\u00ednez","year":"2021","journal-title":"Clin Rheumatol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1128\/CDLI.7.2.241-244.2000","article-title":"Anticardiolipin antibodies in patients with chronic hepatitis C virus infection: characterization in relation to antiphospholipid syndrome","volume":"7","author":"Ordi-Ros","year":"2000","journal-title":"Clin Diagn Lab Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s12879-020-4774-9","article-title":"Mycoplasma pneumoniae pneumonia associated thrombosis at Beijing Children's Hospital","volume":"20","author":"Liu","year":"2020","journal-title":"BMC Infect Dis"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jaut.2018.02.003","article-title":"The treatment of anti-phospholipid syndrome: a comprehensive clinical approach","volume":"90","author":"Chighizola","year":"2018","journal-title":"J Autoimmun"},{"key":"B37","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1111\/j.1538-7836.2006.01753.x","article-title":"International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)","volume":"4","author":"Miyakis","year":"2006","journal-title":"J Thromb Haemost"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ady1681","article-title":"PARP1 stabilizes FOXN3 to suppress pulmonary fibrosis through p38-related feedback regulation","volume":"12","author":"Zhu","year":"2026","journal-title":"Sci Adv"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2023.109822","article-title":"M2 macrophage-derived exosomes induce angiogenesis and increase skin flap survival through HIF1AN\/HIF-1\u03b1\/VEGFA control","volume":"751","author":"Luo","year":"2024","journal-title":"Arch Biochem Biophys"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1845246\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:54:53Z","timestamp":1790744093000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1845246\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":39,"alternative-id":["10.3389\/fimmu.2026.1845246"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1845246","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]},"article-number":"1845246"}}