CpG Can Induce the Proliferation and Differentiation of B10 Cells in the Peripheral Blood of Children with Immune Thrombocytopenic Purpura

Overview

Journal Ann Hematol

Specialty Hematology

Date 2024 Nov 30

PMID 39614925

Authors

Shuge Gu

Min Chen

Wenhao Xu

Han Zhang

Haixia Zhou

Affiliations

Soon will be listed here.

Abstract

Immune thrombocytopenic purpura (ITP) is a disease with a pathogenesis that remains unclear. Accordingly, this study aims to explore the role of B10 cells in ITP pathogenesis and provide a potential novel target for ITP treatment. We selected 42 children diagnosed with ITP and 29 age- and sex-matched healthy children as study objects. Peripheral blood mononuclear cells were isolated and treated with Golgplug combined with CD40L or CpG combined with CD40L, respectively. After 5 h and 48 h in vitro culture, the proportion of B10 cells in CD19 + cells was compared by flow cytometry and intracellular staining between the two groups. ITP children's prognosis was followed up to analyze the relationship between the proportion of B10 cells and the prognosis of ITP. Without CpG stimulation, the proportion of B10 cells in the peripheral blood of ITP children and healthy counterparts did not differ after 5-h in vitro culture. After 48-h in vitro culture, the proportion of B10 cells in the peripheral blood of ITP children without CpG stimulation was significantly higher than in the control group. Under CpG stimulation, the proportion of B10 cells in the peripheral blood of ITP children cultured in vitro was higher than that in the control group. In children with ITP, the proportion of peripheral blood B cells increased. Additionally, CD19 + cells were more sensitive to CpG-induced TLR9 signal stimulation in children with ITP than those in their healthy counterparts. These findings provide a research direction for ITP pathogenesis.

References

Hsiao C . Epstein-Barr virus associated with immune thrombocytopenic purpura in childhood: a retrospective study. J Paediatr Child Health. 2000; 36(5):445-8. DOI: 10.1046/j.1440-1754.2000.00539.x. View

Nelson V, Jolink A, Amini S, Zwaginga J, Netelenbos T, Semple J . Platelets in ITP: Victims in Charge of Their Own Fate?. Cells. 2021; 10(11). PMC: 8621961. DOI: 10.3390/cells10113235. View

Singh G, Bansal D, Wright N . Immune Thrombocytopenia in Children: Consensus and Controversies. Indian J Pediatr. 2020; 87(2):150-157. DOI: 10.1007/s12098-019-03155-4. View

Semple J, Rebetz J, Maouia A, Kapur R . An update on the pathophysiology of immune thrombocytopenia. Curr Opin Hematol. 2020; 27(6):423-429. DOI: 10.1097/MOH.0000000000000612. View

Winiarski J . Mechanisms in childhood idiopathic thrombocytopenic purpura (ITP). Acta Paediatr Suppl. 1998; 424:54-6. DOI: 10.1111/j.1651-2227.1998.tb01235.x. View

Ono K, Onishi Y, Kobayashi M, Ichikawa S, Hatta S, Watanabe S . Successful Treatment of Aggressive Mature B-cell Lymphoma Mimicking Immune Thrombocytopenic Purpura. Intern Med. 2018; 57(17):2573-2579. PMC: 6172554. DOI: 10.2169/internalmedicine.0560-17. View

Giordano P, Cascioli S, Lassandro G, Marcellini V, Cardinale F, Valente F . B-cell hyperfunction in children with immune thrombocytopenic purpura persists after splenectomy. Pediatr Res. 2015; 79(2):262-70. DOI: 10.1038/pr.2015.211. View

Cooper N, Stasi R, Cunningham-Rundles S, Feuerstein M, Leonard J, Amadori S . The efficacy and safety of B-cell depletion with anti-CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura. Br J Haematol. 2004; 125(2):232-9. DOI: 10.1111/j.1365-2141.2004.04889.x. View

Semple J, Milev Y, Cosgrave D, Mody M, Hornstein A, Blanchette V . Differences in serum cytokine levels in acute and chronic autoimmune thrombocytopenic purpura: relationship to platelet phenotype and antiplatelet T-cell reactivity. Blood. 1996; 87(10):4245-54. View

10.

Mouzaki A, Theodoropoulou M, Gianakopoulos I, Vlaha V, Kyrtsonis M, Maniatis A . Expression patterns of Th1 and Th2 cytokine genes in childhood idiopathic thrombocytopenic purpura (ITP) at presentation and their modulation by intravenous immunoglobulin G (IVIg) treatment: their role in prognosis. Blood. 2002; 100(5):1774-9. View

11.

Olsson B, Andersson P, Jernas M, Jacobsson S, Carlsson B, Carlsson L . T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med. 2003; 9(9):1123-4. DOI: 10.1038/nm921. View

12.

Xu J, Du J, Zhong Y, Zhang H, Zhou L, Yao Q . Blockage of CD72 reduces B cell proliferation in immune thrombocytopenic purpura, involving interleukin 1 and macrophage migration inhibitory factor secretion. Hematology. 2022; 27(1):1196-1203. DOI: 10.1080/16078454.2022.2140992. View

13.

Yu H, Liu Y, Han J, Yang Z, Sheng W, Dai H . TLR7 regulates dendritic cell-dependent B-cell responses through BlyS in immune thrombocytopenic purpura. Eur J Haematol. 2010; 86(1):67-74. DOI: 10.1111/j.1600-0609.2010.01534.x. View

14.

Krakauer T . Differential inhibitory effects of interleukin-10, interleukin-4, and dexamethasone on staphylococcal enterotoxin-induced cytokine production and T cell activation. J Leukoc Biol. 1995; 57(3):450-4. DOI: 10.1002/jlb.57.3.450. View

15.

Matsushita T, Horikawa M, Iwata Y, Tedder T . Regulatory B cells (B10 cells) and regulatory T cells have independent roles in controlling experimental autoimmune encephalomyelitis initiation and late-phase immunopathogenesis. J Immunol. 2010; 185(4):2240-52. PMC: 3717968. DOI: 10.4049/jimmunol.1001307. View

16.

Zheng Z, Liu T, Li X, Ding J, Feng Y, Miao J . Kinetic changes of regulatory B10 cells in collagen-induced arthritis could be regulated by cytokines IFN-γ and TGF-β1. Inflamm Res. 2015; 64(8):637-45. DOI: 10.1007/s00011-015-0846-5. View

17.

Berry G, Budgeon L, Cooper T, Christensen N, Waldner H . The type 1 diabetes resistance locus B10 Idd9.3 mediates impaired B-cell lymphopoiesis and implicates microRNA-34a in diabetes protection. Eur J Immunol. 2014; 44(6):1716-27. DOI: 10.1002/eji.201344116. View

18.

Yuan C, Li X, Luo L, Wang Y, Zhang D, Zhou K . Mannose-capped lipoarabinomannan-induced B10 cells decrease severity of dextran sodium sulphate-induced inflammatory bowel disease in mice. Scand J Immunol. 2019; 91(2):e12843. PMC: 7050505. DOI: 10.1111/sji.12843. View

19.

Maekawa T, Osawa Y, Okada Y, Tachi N, Teramoto M, Kawamura T . Low mucosal-associated invariant T-cell number in peripheral blood of patients with immune thrombocytopenia and their response to prednisolone. PLoS One. 2018; 13(11):e0207149. PMC: 6224073. DOI: 10.1371/journal.pone.0207149. View

20.

Cooper N, Kruse A, Kruse C, Watson S, Morgan M, Provan D . Immune thrombocytopenia (ITP) World Impact Survey (I-WISh): Impact of ITP on health-related quality of life. Am J Hematol. 2020; 96(2):199-207. PMC: 7898815. DOI: 10.1002/ajh.26036. View