Immune Features of Complement, Immunoglobulins, and Lymphocyte Subsets in Childhood Immune Thrombocytopenia
-
Mengchun Chen
,
Ling Hu
,
Jing Xue
,
Biao Liu
,
Meng Chang
Abstract
Immune thrombocytopenia (ITP), the commonest pediatric acquired bleeding disorder, involves immune dysregulation; assessing C3/C4, Ig(G/A/M), and lymphocyte subsets has diagnostic value.
A retrospective study enrolled 40 children with ITP (0–18 years, meeting pediatric ITP criteria) admitted to our hospital (January 2023 to March 2025) as the ITP group, and 40 healthy children as controls. Serum IgG, IgA, IgM, C3, C4, lymphocyte subsets (CD3+, CD4+, and CD8+ T cells, CD19+ B cells, and CD16+CD56+ NK cells), autoimmune antibodies, TORCH, EBV, and CMV status were detected. Pearson correlation and receiver operating characteristic curves analyzed correlations and diagnostic efficacy of single/combined indicators, and multivariate logistic regression was used for statistical analysis.
Baseline data were balanced. Compared with controls, ITP patients had higher IgG, lower IgM, C3 and C4, similar IgA; lower CD3⁺ and CD4⁺ percentages and CD4⁺:CD8⁺ ratio, higher CD8⁺ cells, similar CD16⁺/CD56⁺ and CD19⁺; and higher epstein-barr virus/cytomegalovirus and autoantibody positivity. Pearson analysis showed reduced CD4⁺, CD3⁺, C3, C4 and elevated CD8⁺, IgG correlated with lower platelet count. ROC of combined CD4⁺, CD8⁺, C3, C4, IgG gave AUC 0.967, sensitivity 92.5%, specificity 90.0%, outperforming single indices.
Children with ITP have abnormal immunoglobulins, inadequate complement activation, and imbalanced lymphocyte subsets; combined detection of these aids ITP diagnosis and provides clinical basis.
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12. Bu S, Liu M, Yang L, Lee P, Miller H, Park CS, et al. The function of T cells in immune thrombocytopenia. Front Immunol. 2025;16:1499014.
13. Zahran AM, El-Badawy OH, Mahran H, Gad E, Saad K, Morsy SG, et al. Detection and characterization of autoreactive memory stem T-cells in children with acute immune thrombocytopenia. Clin Exp Med. 2024 Jul 15;24(1):158..
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15. Chinese Children's Primary Immune Thrombocytopenia Diagnosis and Treatment Guidelines Adaptation Working Group HGotCMAPB, Editorial Committee of Chinese Pediatric Journal. Adapted guideline for the diagnosis and treatment of primary immune thrombocytopenia for Chinese children (2021). Chinese Journal of Pediatrics. 2021,59(10):810-819.
16. Hillier K, MacMath D, Chumsky J, Kirk SE, O'Farrell C, Kim TO, et al. Immunoglobulins act as predictors of chronicity in pediatric immune thrombocytopenia. Blood Adv. 2024;8(19):5118-21.
17. Castelli R, Lambertenghi Delilliers G, Gidaro A, Cicardi M, Bergamaschini L. Complement activation in patients with immune thrombocytopenic purpura according to phases of disease course. Clin Exp Immunol. 2020;201(3):258-65.
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21. Li J, Wang X, Chen Y, Sun X, Fu L, Xin Q, et al. Exosome-Mediated Lectin Pathway and Resistin-MIF-AA Metabolism Axis Drive Immune Dysfunction in Immune Thrombocytopenia. Adv Sci (Weinh). 2025;12(10):e2412378.
22. Shindo R, Abe R, Oku K, Tanaka T, Matsueda Y, Wada T, et al. Involvement of the complement system in immune thrombocytopenia: review of the literature. Immunol Med. 2023;46(4):182-90.
23. Cheloff AZ KD, Al-Samkari H. Serum complement levels in immune thrombocytopenia: Characterization and relation to clinical features. Res Pract Thromb Haemost. 2020;4(5):807-12.
24. Nasr NM, Ayad AA, Abdelghaffar NK, Mohamed MS. The correlation between serum complement levels and clinical presentation in Egyptian immune thrombocytopenia patients. Blood Res. 2025;60(1):29.
25. Zahran AM, Elsayh KI. CD4+ CD25+High Foxp3+ regulatory T cells, B lym phocytes, and T lymphocytes in patients with acute ITP in Assiut Children Hospital. Clin Appl Thromb Hemost. 2014;20(1):61-7.
26. Schmidt DE, Heitink-Pollé KMJ, Nicolet BP, Porcelijn L, Bruin MCA, Weterings N, et al. Increased effector memory CD4(+) T cells are associated with chronic childhood immune thrombocytopenia. J Thromb Haemost. 2025;23(9):2969-81.
27. Pratt EL, Tarantino MD, Wagner D, Hirsch Pescovitz O, Bowyer S, Shapiro AD. Prevalence of elevated antithyroid antibodies and antinuclear antibodies in children with immune thrombocytopenic purpura. Am J Hematol. 2005;79(3):175-9.
28. Rinaldi M, Perricone C, Ortega-Hernandez OD, Perricone R, Shoenfeld Y. Immune thrombocytopaenic purpura: an autoimmune cross-link between infections and vaccines. Lupus. 2014;23(6):554-67.
29. Wang W, Tao S, Zhang X, Wang W, Xu Y, Liang W. The Value of Combined Detection of Megakaryocyte and Platelet Parameters for the Diagnosis of Primary Immune Thrombocytopenia. Clin Appl Thromb Hemost. 2022;28:10760296221106779.
30. Nakhaei Shamahmood M, Tavakoli K, Rafat B, Miri A, Ahmadi MH, Sadeghi-Bojd Y. Evaluation of Hemato-Inflammatory Parameters NLR, PLR and HPR in Patients with Immune Thrombocytopenic Purpura (ITP) in South-East Iran: A Retrospective Study. Clin Appl Thromb Hemost. 2025;31:10760296251384282.
31. Heidari N, Hosseini E, Faranoush M, Pezeshki SMS, Teimourpour A, Gardiner EE, et al. A design for an efficient functional panel that determines platelet exhaustion levels to differentiate responder and non-responder ITP patients. Sci Rep. 2025;15(1):38271.
2. Semple JW, Schifferli A, Cooper N, Saad H, Mytych DT, Chea LS, et al. Immune thrombocytopenia: Pathophysiology and impacts of Romiplostim treatment. Blood Reviews. 2024;67:101222.
3. Chen W, Kan H, Qin M, Yang J, Tao W, XiaoYang. Investigation of the Active Compounds and Important Pathways of Huaiqihuang Granule for the Treatment of Immune Thrombocytopenia Using Network Pharmacology and Molecular Docking. Biomed Res Int. 2023;2023:5984361.
4. Abbasi F, Kaydani GA, Tahannezhad Z, Nakhaie M, Asnafi AA, Moradi M. Prevalence of Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) Subclinical Infection in Patients with Acute Immune Thrombocytopenic Purpura (ITP). Int J Hematol Oncol Stem Cell Res. 2021;15(3):139-44.
5. Weitz IC, Liebman HA. Complement in immune thrombocytopenia (ITP): The role of complement in refractory ITP. Br J Haematol. 2023;203(1):96-100.
6. Toltl LJ, Nazi I, Jafari R, Arnold DM. Piecing together the humoral and cellular mechanisms of immune thrombocytopenia. Semin Thromb Hemost. 2011;37(6):631-9.
7. Tariq Z, Qadeer MI, Zahid K, Cherepkova EV, Olzhayev ST. Immune Thrombocytopenia: Immune Dysregulation and Genetic Perturbations Deciphering the Fate of Platelets. Front Biosci (Landmark Ed). 2024;29(10):342.
8. Jankowski J, Nijakowski K. Salivary Immunoglobulin a Alterations in Health and Disease: A Bibliometric Analysis of Diagnostic Trends from 2009 to 2024. Antibodies. 2024;13(4):98.
9. Guo X, Wang K, Liu Q, Baran N, Ma W. The gut-immune axis in primary immune thrombocytopenia (ITP): a paradigm shifts in treatment approaches. Front Immunol. 2025;16:1595977.
10. De Menezes Costa SS, Girardo B, Silva TC, Ziza K, Ribeiro G, Langhi DM, et al. The hemolytic activity of abo antibodies: Correlation between quantitative tests, complement‐mediated hemolysis assay (CHUHE‐P), and IgG subclasses. Transfus Med. 2025;35(5):458-69.
11. Sun L, Zhang Y, Chen P, Jiang N, Feng Q, Xu S, et al. The effects of complement-independent, autoantibody-induced apoptosis of platelets in immune thrombocytopenia (ITP). Ann Hematol. 2024;103(12):5157-68.
12. Bu S, Liu M, Yang L, Lee P, Miller H, Park CS, et al. The function of T cells in immune thrombocytopenia. Front Immunol. 2025;16:1499014.
13. Zahran AM, El-Badawy OH, Mahran H, Gad E, Saad K, Morsy SG, et al. Detection and characterization of autoreactive memory stem T-cells in children with acute immune thrombocytopenia. Clin Exp Med. 2024 Jul 15;24(1):158..
14. David P, Santos GdM, Patt YS, Orsi FA, Shoenfeld Y. Immune thrombocytopenia (ITP) - could it be part of autoimmune/inflammatory syndrome induced by adjuvants (ASIA)? Autoimmun Rev. 2024;23(9):103605.
15. Chinese Children's Primary Immune Thrombocytopenia Diagnosis and Treatment Guidelines Adaptation Working Group HGotCMAPB, Editorial Committee of Chinese Pediatric Journal. Adapted guideline for the diagnosis and treatment of primary immune thrombocytopenia for Chinese children (2021). Chinese Journal of Pediatrics. 2021,59(10):810-819.
16. Hillier K, MacMath D, Chumsky J, Kirk SE, O'Farrell C, Kim TO, et al. Immunoglobulins act as predictors of chronicity in pediatric immune thrombocytopenia. Blood Adv. 2024;8(19):5118-21.
17. Castelli R, Lambertenghi Delilliers G, Gidaro A, Cicardi M, Bergamaschini L. Complement activation in patients with immune thrombocytopenic purpura according to phases of disease course. Clin Exp Immunol. 2020;201(3):258-65.
18. Broome CM, Röth A, Kuter DJ, Scully M, Smith R, Wang J, et al. Safety and efficacy of classical complement pathway inhibition with sutimlimab in chronic immune thrombocytopenia. Blood Adv. 2023;7(6):987-96.
19. Wang T, He X, Ran N, Liu C, Xing L, Wang H, et al. Immunological characteristics and effect of cyclosporin in patients with immune thrombocytopenia. J Clin Lab Anal. 2021;35(9):e23922..
20. Li Q, Marcoux G, Hu Y, Rebetz J, Guo L, Semple E, et al. Autoimmune effector mechanisms associated with a defective immunosuppressive axis in immune thrombocytopenia (ITP). Autoimmun Rev. 2024;23(12):103677.
21. Li J, Wang X, Chen Y, Sun X, Fu L, Xin Q, et al. Exosome-Mediated Lectin Pathway and Resistin-MIF-AA Metabolism Axis Drive Immune Dysfunction in Immune Thrombocytopenia. Adv Sci (Weinh). 2025;12(10):e2412378.
22. Shindo R, Abe R, Oku K, Tanaka T, Matsueda Y, Wada T, et al. Involvement of the complement system in immune thrombocytopenia: review of the literature. Immunol Med. 2023;46(4):182-90.
23. Cheloff AZ KD, Al-Samkari H. Serum complement levels in immune thrombocytopenia: Characterization and relation to clinical features. Res Pract Thromb Haemost. 2020;4(5):807-12.
24. Nasr NM, Ayad AA, Abdelghaffar NK, Mohamed MS. The correlation between serum complement levels and clinical presentation in Egyptian immune thrombocytopenia patients. Blood Res. 2025;60(1):29.
25. Zahran AM, Elsayh KI. CD4+ CD25+High Foxp3+ regulatory T cells, B lym phocytes, and T lymphocytes in patients with acute ITP in Assiut Children Hospital. Clin Appl Thromb Hemost. 2014;20(1):61-7.
26. Schmidt DE, Heitink-Pollé KMJ, Nicolet BP, Porcelijn L, Bruin MCA, Weterings N, et al. Increased effector memory CD4(+) T cells are associated with chronic childhood immune thrombocytopenia. J Thromb Haemost. 2025;23(9):2969-81.
27. Pratt EL, Tarantino MD, Wagner D, Hirsch Pescovitz O, Bowyer S, Shapiro AD. Prevalence of elevated antithyroid antibodies and antinuclear antibodies in children with immune thrombocytopenic purpura. Am J Hematol. 2005;79(3):175-9.
28. Rinaldi M, Perricone C, Ortega-Hernandez OD, Perricone R, Shoenfeld Y. Immune thrombocytopaenic purpura: an autoimmune cross-link between infections and vaccines. Lupus. 2014;23(6):554-67.
29. Wang W, Tao S, Zhang X, Wang W, Xu Y, Liang W. The Value of Combined Detection of Megakaryocyte and Platelet Parameters for the Diagnosis of Primary Immune Thrombocytopenia. Clin Appl Thromb Hemost. 2022;28:10760296221106779.
30. Nakhaei Shamahmood M, Tavakoli K, Rafat B, Miri A, Ahmadi MH, Sadeghi-Bojd Y. Evaluation of Hemato-Inflammatory Parameters NLR, PLR and HPR in Patients with Immune Thrombocytopenic Purpura (ITP) in South-East Iran: A Retrospective Study. Clin Appl Thromb Hemost. 2025;31:10760296251384282.
31. Heidari N, Hosseini E, Faranoush M, Pezeshki SMS, Teimourpour A, Gardiner EE, et al. A design for an efficient functional panel that determines platelet exhaustion levels to differentiate responder and non-responder ITP patients. Sci Rep. 2025;15(1):38271.
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| Complement system proteins Idiopathic Immunoglobulins Lymphocyte subsets Purpura Thrombocytopenic | ||
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How to Cite
1.
Chen M, Hu L, Xue J, Liu B, Chang M. Immune Features of Complement, Immunoglobulins, and Lymphocyte Subsets in Childhood Immune Thrombocytopenia. Iran J Allergy Asthma Immunol. 2026;:1-12.
