Monocyte-Derived Chemokines in Immune Thrombocytopenia: Diagnostic and Pathogenic Insights from a Cross-Sectional Case-Control Study

Hasan Göze; Ahmet Muzaffer Demir

doi:10.18521/ktd.1892413

Monocyte-Derived Chemokines in Immune Thrombocytopenia: Diagnostic and Pathogenic Insights from a Cross-Sectional Case-Control Study

Abstract

Aim: Immune thrombocytopenia (ITP) is an autoimmune disorder with incompletely understood immunopathogenesis. This study aimed to evaluate the serum levels of monocyte-derived chemokines—CCL1, CCL3, CCL4, and CCL16—in newly diagnosed ITP patients, with a focus on their potential diagnostic and pathogenic relevance.

Material and Methods: In a cross-sectional case-control design, 84 patients with primary ITP and 84 age- and sex-matched healthy controls were included. Serum chemokine concentrations were measured using ELISA.

Results: CCL4 levels were significantly elevated in ITP patients (p < 0.001) and emerged as an independent predictor (OR = 1.158, p = 0.005). CCL1 levels were moderately increased (p = 0.038), and CCL3 reached statistical significance after outlier correction (p = 0.015). No significant differences were observed for CCL16. The logistic regression model yielded an overall classification accuracy of 82.1%, with ROC analysis supporting the potential diagnostic utility of CCL4.

Conclusion: CCL4 may serve as a useful biomarker in the diagnosis and immunological assessment of ITP. Although CCL1 and CCL3 also showed some associations with disease status, further research is needed to clarify their clinical significance. Chemokine profiling may enhance the understanding of ITP’s immune mechanisms and support clinical monitoring strategies.

Keywords

References

Mititelu A, Onisâi MC, Roșca A, Vlădăreanu AM. Current understanding of immune thrombocytopenia: a review of pathogenesis and treatment options. Int J Mol Sci. 2024;25(4):2163. doi:10.3390/ijms25042163.
Zufferey A, Kapur R, Semple JW. Pathogenesis and Therapeutic Mechanisms in Immune Thrombocytopenia (ITP). J Clin Med. 2017;6(2):16. doi:10.3390/jcm6020016.
Kosmidou A, Gavriilaki E, Tragiannidis A. The challenge for a correct diagnosis of refractory thrombocytopenia: ITP or MDS with isolated thrombocytopenia? Cancers (Basel). 2024;16(8):1462. doi:10.3390/cancers16081462.
Liu XG, Hou Y, Hou M. How we treat primary immune thrombocytopenia in adults. J Hematol Oncol. 2023;16(1):4. doi:10.1186/s13045-023-01401-z.
Liang T, Yi H, Guo H, Xie Y, Hu J, Chen Y. lncRNA GAS 5 rs145204276 as a risk factor for primary immune thrombocytopenia in the Chinese Han population. Expert Rev Hematol. 2025;18(3):283-9. doi:10.1080/17474086.2025.2483669.
Kistangari G, McCrae KR. Immune thrombocytopenia. Hematol Oncol Clin North Am. 2013;27(3):495-520. doi:10.1016/j.hoc.2013.03.001.
Karin N, Wildbaum G. The role of chemokines in adjusting the balance between CD4+ effector T cell subsets and FOXp3-negative regulatory T cells. Int Immunopharmacol. 2015;28(2):829-35. doi:10.1016/j.intimp.2015.03.037.
Choi J, Selmi C, Leung PS, Kenny TP, Roskams T, Gershwin ME. Chemokine and chemokine receptors in autoimmunity: the case of primary biliary cholangitis. Expert Rev Clin Immunol. 2016;12(6):661-72. doi:10.1586/1744666X.2016.1147956.

Medrano-Bosch M, Simón-Codina B, Jiménez W, Edelman ER, Melgar-Lesmes P. Monocyte-endothelial cell interactions in vascular and tissue remodeling. Front Immunol. 2023;14:1196033. doi:10.3389/fimmu.2023.1196033.
Xu H, Lin S, Zhou Z, Li D, Zhang X, Yu M, et al. New genetic and epigenetic insights into the chemokine system: the latest discoveries aiding progression toward precision medicine. Cell Mol Immunol. 2023;20(7):739-76. doi:10.1038/s41423-023-01032-x.
Perera M, Garrido T. Advances in the pathophysiology of primary immune thrombocytopenia. Hematology. 2017;22(1):41-53. doi:10.1080/10245332.2016.1219497.
Bussel JB, de Miguel PG, Despotovic JM, Grainger JD, Sevilla J, Blanchette VS, et al. Eltrombopag for the treatment of children with persistent and chronic immune thrombocytopenia (PETIT): a randomised, multicentre, placebo-controlled study. Lancet Haematol. 2015;2(8):e315-25. doi:10.1016/S2352-3026(15)00114-3.
Whitworth H, Amankwah EK, Betensky M, Castellucci LA, Cuker A, Goldenberg NA, et al. Updated guidance for efficacy and safety outcomes for clinical trials in venous thromboembolism in children: communication from the ISTH SSC Subcommittee on Pediatric and Neonatal Thrombosis and Hemostasis. J Thromb Haemost. 2023;21(6):1666-73. doi:10.1016/j.jtha.2023.03.004.
Grygorczuk S, Zajkowska J, Swierzbińska R, Pancewicz S, Kondrusik M, Hermanowska-Szpakowicz T. Elevated concentration of the chemokine CCL3 (MIP-1alpha) in cerebrospinal fluid and serum of patients with tick borne encephalitis. Adv Med Sci. 2006;51:340-4.
Consolini R, Legitimo A, Caparello MC. The centenary of immune thrombocytopenia - Part 1: revising nomenclature and pathogenesis. Front Pediatr. 2016;4:102. doi:10.3389/fped.2016.00102.
Peña-Valencia K, Riaño W, Herrera-Diaz M, López L, Marín D, Gonzalez S, et al. Markers of inflammation, tissue damage, and fibrosis in individuals diagnosed with human immunodeficiency virus and pneumonia: a cohort study. Pathogens. 2024;13(1):84. doi:10.3390/pathogens13010084.
Ellwanger JH, Kulmann-Leal B, Kaminski VL, Rodrigues AG, Bragatte MAS, Chies JAB. Beyond HIV infection: Neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases. Virus Res. 2020;286:198040. doi:10.1016/j.virusres.2020.198040.
Stimpson ML, Lait PJP, Schewitz-Bowers LP, Williams EL, Thirlwall KF, Lee RWJ, et al. IL-10 and IL-17 expression by CD4(+) T cells is altered in corticosteroid refractory immune thrombocytopenia (ITP). J Thromb Haemost. 2020;18(10):2712-20. doi:10.1111/jth.14970.
Williams EL, Stimpson ML, Lait PJP, Schewitz-Bowers LP, Jones LV, Dhanda AD, et al. Glucocorticoid treatment in patients with newly diagnosed immune thrombocytopenia switches CD14(++) CD16(+) intermediate monocytes from a pro-inflammatory to an anti-inflammatory phenotype. Br J Haematol. 2021;192(2):375-84. doi:10.1111/bjh.17205.
Denis C, Deiteren K, Mortier A, Tounsi A, Fransen E, Proost P, et al. C-terminal clipping of chemokine CCL1/I-309 enhances CCR8-mediated intracellular calcium release and anti-apoptotic activity. PLoS One. 2012;7(3):e34199. doi:10.1371/journal.pone.0034199.
Abohassan M, Al Shahrani M, Alshahrani MY, Begum N, Radhakrishnan S, Rajagopalan P. FNF-12, a novel benzylidene-chromanone derivative, attenuates inflammatory response in in vitro and in vivo asthma models mediated by M2-related Th2 cytokines via MAPK and NF-kB signaling. Pharmacol Rep. 2022;74(1):96-110. doi:10.1007/s43440-021-00325-0.
Galeano Niño JL, Pageon SV, Tay SS, Colakoglu F, Kempe D, Hywood J, et al. Cytotoxic T cells swarm by homotypic chemokine signalling. Elife. 2020;9:e56554. doi:10.7554/eLife.56554.
Carvalho JC, Pascoal-Xavier MA, Araújo MG, Martins JP, Teixeira-Carvalho A, Gomes MS, et al. Immune mediators as plasma biomarkers for identifying household contacts and classifying clinical forms and leprosy reactions. Front Immunol. 2025;16:1513060. doi:10.3389/fimmu.2025.1513060.
Dai Z, Wang Y, Sun N, Zhang C. Characterizing ligand-receptor interactions and unveiling the pro-tumorigenic role of CCL16-CCR1 axis in the microenvironment of hepatocellular carcinoma. Front Immunol. 2023;14:1299953. doi:10.3389/fimmu.2023.1299953.
Chi HC, Lin YH, Wu YH, Chang CC, Wu CH, Yeh CT, et al. CCL16 is a pro-tumor chemokine that recruits monocytes and macrophages to promote hepatocellular carcinoma progression. Am Journal Cancer Res. 2024;14(7):3600-13. doi:10.62347/VCTW6889.
Zhang L, Zhang M, Wang L, Li J, Yang T, Shao Q, et al. Identification of CCL4 as an immune-related prognostic biomarker associated with tumor proliferation and the tumor microenvironment in clear cell renal cell carcinoma. Front Oncol. 2021;11:694664. doi:10.3389/fonc.2021.694664.

Details

Primary Language

English

Subjects

Health Informatics and Information Systems

Journal Section

Research Article

Authors

Hasan Göze ^*
0000-0001-7397-1877
Türkiye

Ahmet Muzaffer Demir
0000-0002-2073-5405
Türkiye

Publication Date

June 26, 2026

Submission Date

February 18, 2026

Acceptance Date

May 11, 2026

Published in Issue

Year 2026 Volume: 18 Number: 2

DOI

https://doi.org/10.18521/ktd.1892413

IZ

https://izlik.org/JA33YS44DB

Cite

RIS / Bibtex

APA

Göze, H., & Demir, A. M. (2026). Monocyte-Derived Chemokines in Immune Thrombocytopenia: Diagnostic and Pathogenic Insights from a Cross-Sectional Case-Control Study. Konuralp Medical Journal, 18(2), 128-134. https://doi.org/10.18521/ktd.1892413

AMA

1.Göze H, Demir AM. Monocyte-Derived Chemokines in Immune Thrombocytopenia: Diagnostic and Pathogenic Insights from a Cross-Sectional Case-Control Study. Konuralp Medical Journal. 2026;18(2):128-134. doi:10.18521/ktd.1892413

Chicago

Göze, Hasan, and Ahmet Muzaffer Demir. 2026. “Monocyte-Derived Chemokines in Immune Thrombocytopenia: Diagnostic and Pathogenic Insights from a Cross-Sectional Case-Control Study”. Konuralp Medical Journal 18 (2): 128-34. https://doi.org/10.18521/ktd.1892413.

EndNote

Göze H, Demir AM (June 1, 2026) Monocyte-Derived Chemokines in Immune Thrombocytopenia: Diagnostic and Pathogenic Insights from a Cross-Sectional Case-Control Study. Konuralp Medical Journal 18 2 128–134.

IEEE

[1]H. Göze and A. M. Demir, “Monocyte-Derived Chemokines in Immune Thrombocytopenia: Diagnostic and Pathogenic Insights from a Cross-Sectional Case-Control Study”, Konuralp Medical Journal, vol. 18, no. 2, pp. 128–134, June 2026, doi: 10.18521/ktd.1892413.

ISNAD

Göze, Hasan - Demir, Ahmet Muzaffer. “Monocyte-Derived Chemokines in Immune Thrombocytopenia: Diagnostic and Pathogenic Insights from a Cross-Sectional Case-Control Study”. Konuralp Medical Journal 18/2 (June 1, 2026): 128-134. https://doi.org/10.18521/ktd.1892413.

JAMA

1.Göze H, Demir AM. Monocyte-Derived Chemokines in Immune Thrombocytopenia: Diagnostic and Pathogenic Insights from a Cross-Sectional Case-Control Study. Konuralp Medical Journal. 2026;18:128–134.

MLA

Göze, Hasan, and Ahmet Muzaffer Demir. “Monocyte-Derived Chemokines in Immune Thrombocytopenia: Diagnostic and Pathogenic Insights from a Cross-Sectional Case-Control Study”. Konuralp Medical Journal, vol. 18, no. 2, June 2026, pp. 128-34, doi:10.18521/ktd.1892413.

Vancouver

1.Hasan Göze, Ahmet Muzaffer Demir. Monocyte-Derived Chemokines in Immune Thrombocytopenia: Diagnostic and Pathogenic Insights from a Cross-Sectional Case-Control Study. Konuralp Medical Journal. 2026 Jun. 1;18(2):128-34. doi:10.18521/ktd.1892413