Diagnostic and predictive relevance of protein tyrosine phosphatase receptor type C serum levels and rs10919563 variant in rheumatoid arthritis and tumor necrosis factor inhibitor outcomes

  • A. H. Kamel Al-Iraqia University
  • A. A. Abbas Al-Nahrain University
  • M. H. Alosami University of Baghdad
Keywords: rheumatoid arthritis, PTPRC, rs10919563 polymorphism, tumor necrosis factor inhibitors.

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by the central role of immune dysregulation. There is growing evidence linking the pathophysiology of some autoimmune disorders to protein tyrosine phosphatase receptor typ e C (PTPRC), a crucial modulator of immune cell communication. The current study's objective was to assess the predictive and diagnostic ability of rs10919563 polymorphism and serum PTPRC levels in relation to RA patients' disease activity and tumor necrosis factor (TNF) inhibitor responsiveness. One hundred RA patients and one hundred healthy controls were subjected to case-control analysis. En zyme-linked immunosorbent assa y (ELISA) was used to measure serum PTPRC levels, and TaqMan real-time PCR was used to genotype PTPRC rs10919563. Following six months of TNF inhibitor treatment, scores from the clinical disease activity i ndex (CDAI) were assessed to measure disease activity and medication response. Area under the curve (AUC) = 0.979 indicated very strong diagno s tic performance, and serum PTPRC concentrations were considerably greater in RA patients than in controls. Higher disease activity and a decreased responsiveness to TNF inhibitors were linked to the AA genotype and the A allele of rs10919563. Higher serum levels of PTPRC as well as AA genotype also correlated with higher CDAI scores. In patients with RA, elevated serum levels of PTPRC and polymorphism rs10919563 are linked to high disease activity and poor therapy response. These results support PTPRC's potential clinical use as a RA biomarker for diagnosis, follow-up, and customized treatment.

References

Awni, A. A., Hamed, Z. O., Abdul-Hassan Abbas, A., & Abdulamir, A. S. (2023). Effect of NLRP3 inflammasome genes polymorphism on disease susceptibility and response to TNF-α inhibitors in Iraqi patients with rheumatoid arthritis. Heliyon, 9(6), e16814.

Bedeković, D., Bošnjak, I., Bilić-Ćurčić, I., Kirner, D., Šarić, S., & Novak, S. (2024). Risk for cardiovascular disease development in rheumatoid arthritis. BMC Cardiovascular Disorders, 24(1), 291.

Bek, S., Bojesen, A. B., Nielsen, J. V., Sode, J., Bank, S., Vogel, U., & Andersen, V. (2017). Systematic review and meta-analysis: pharmacogenetics of anti-TNF treatment response in rheumatoid arthritis. The Pharmacogenomics Journal, 17(5), 403–411.

Brown, P., Pratt, A. G., & Hyrich, K. L. (2024). Therapeutic advances in rheumatoid arthritis. British Medical Journal, 384, e070856.

Canhão, H., Rodrigues, A. M., Santos, M. J., Carmona-Fernandes, D., Bettencourt, B. F., Cui, J., Rocha, F. L., Canas Silva, J., Polido-Pereira, J., Pereira Silva, J. A., Costa, J. A., Araujo, D., Silva, C., Santos, H., Duarte, C., Cáliz, R., Filipescu, I., Pimentel-Santos, F., Branco, J., … Karlson, E. W. (2015). TRAF1/C5 but not PTPRC variants are potential predictors of rheumatoid arthritis response to anti-tumor necrosis factor therapy. BioMed Research International, 2015, 490295.

Castañeda, S., López-Mejías, R., & González-Gay, M. A. (2016). Gene polymorphisms and therapy in rheumatoid arthritis. Expert Opinion on Drug Metabolism and Toxicology, 12(3), 225–229.

Chang, K., Yang, S., Kim, S., Han, K., Park, S., & Shin, J. (2014). Smoking and rheumatoid arthritis. International Journal of Molecular Sciences, 15(12), 22279–22295.

Cooper, D. N. (2010). Functional intronic polymorphisms: Buried treasure awaiting discovery within our genes. Human Genomics, 4(5), 284.

Cui, J., Saevarsdottir, S., Thomson, B., Padyukov, L., van der Helm‐Van Mil, A. H. M., Nititham, J., Hughes, L. B., de Vries, N., Raychaudhuri, S., Alfredsson, L., Askling, J., Wedrén, S., Ding, B., Guiducci, C., Wolbink, G. J., Crusius, J. B. A., van der Horst-Bruinsma, I. E., Herenius, M., Weinblatt, M. E., … Plenge, R. M. (2010). Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor α therapy. Arthritis and Rheumatism, 62(7), 1849–1861.

Daghestani, M., Othman, N., Omair, M. A., Alenzi, F., Omair, M. A., Alqurtas, E., Amin, S., & Warsy, A. (2023). Single nucleotide polymorphisms associated with rheumatoid arthritis in Saudi patients. Journal of Clinical Medicine, 12(15), 4944.

Edilova, M. I., Akram, A., & Abdul-Sater, A. A. (2021). Innate immunity drives pathogenesis of rheumatoid arthritis. Biomedical Journal, 44(2), 172–182.

Feng, X., Xu, X., Shi, Y., Liu, X., Liu, H., Hou, H., Ji, L., Li, Y., Wang, W., Wang, Y., & Li, D. (2019). Body mass index and the risk of rheumatoid arthritis: An updated dose-response meta-analysis. BioMed Research International, 2019, 3579081.

Ferreiro-Iglesias, A., Montes, A., Perez-Pampin, E., Cañete, J. D., Raya, E., Magro-Checa, C., Vasilopoulos, Y., Sarafidou, T., Caliz, R., Ferrer, M. A., Joven, B., Carreira, P., Balsa, A., Pascual-Salcedo, D., Blanco, F. J., Moreno-Ramos, M. J., Fernández-Nebro, A., Ordóñez, M. C., Alegre-Sancho, J. J., … Gonzalez, A. (2015). Replication of PTPRC as genetic biomarker of response to TNF inhibitors in patients with rheumatoid arthritis. The Pharmacogenomics Journal, 16(2), 137–140.

Frisell, T., Saevarsdottir, S., & Askling, J. (2016). Family history of rheumatoid arthritis: An old concept with new developments. Nature Reviews Rheumatology, 12(6), 335–343.

Gilani, S. S., Nair, N., Plant, D., Hyrich, K., Morgan, A. W., Morris, A. P., Wilson, A. G., Isaacs, J. D., Barton, A., & Bluett, J. (2020). Pharmacogenetics of Tnf Inhibitor response in rheumatoid arthritis utilizing the two-component disease activity score. Pharmacogenomics, 21(16), 1151–1156.

Jumaah Fadhil, Z., Abdul- Hassan Abbas, A., & Hadi Al-Osami, M. (2023). The influence of TNFRSF1B, PADI4, and miRNA 499 gene polymorphisms on susceptibility and responsiveness to TNF inhibitors in patients with rheumatoid arthritis. Journal of Advances in Medical and Biomedical Research, 31(147), 381–390.

Lateef, S. M., Abdul-Hassan Abbas, A., & Alosami, M. H. (2025). Relationship between trough levels of anti-Infliximab and serum biomarkers in patients with rheumatoid arthritis. Acta Medica Iranica, 62(6), 338–345.

Lopez-Pedrera, C., Barbarroja, N., Patiño-Trives, A. M., Luque-Tévar, M., Collantes-Estevez, E., Escudero-Contreras, A., & Pérez-Sánchez, C. (2020). Effects of biological therapies on molecular features of rheumatoid arthritis. International Journal of Molecular Sciences, 21(23), 9067.

Lu, B., Hiraki, L. T., Sparks, J. A., Malspeis, S., Chen, C.-Y., Awosogba, J. A., Arkema, E. V., Costenbader, K. H., & Karlson, E. W. (2014). Being overweight or obese and risk of developing rheumatoid arthritis among women: A prospective cohort study. Annals of the Rheumatic Diseases, 73(11), 1914–1922.

Mikhaylenko, D. S., Nemtsova, M. V., Bure, I. V., Kuznetsova, E. B., Alekseeva, E. A., Tarasov, V. V., Lukashev, A. N., Beloukhova, M. I., Deviatkin, A. A., & Zamyatnin, A. A. (2020). Genetic polymorphisms associated with rheumatoid arthritis development and antirheumatic therapy response. International Journal of Molecular Sciences, 21(14), 4911.

O’Neil, L. J., Alpízar-Rodríguez, D., & Deane, K. D. (2024). Rheumatoid arthritis: The continuum of disease and strategies for prediction, early intervention, and prevention. The Journal of Rheumatology, 51(4), 337–349.

Plant, D., Prajapati, R., Hyrich, K. L., Morgan, A. W., Wilson, A. G., Isaacs, J. D., & Barton, A. (2012). Replication of association of the PTPRC gene with response to anti-tumor necrosis factor therapy in a large UK cohort. Arthritis and Rheumatism, 64(3), 665–670.

Qi, X., Fu, J., Liu, J., Wu, X., Zheng, X., & Wang, S. (2024). Association between second hand smoke exposure and rheumatoid arthritis in US never-smoking adults: A cross-sectional study from NHANES. Scientific Reports, 14(1), 11061.

Rheinländer, A., Schraven, B., & Bommhardt, U. (2018). CD45 in human physiology and clinical medicine. Immunology Letters, 196, 22–32.

Rija, F. F., Hussein, S. Z., & Abdalla, M. A. (2021). Physiological and immunological disturbance in rheumatoid arthritis patients. Baghdad Science Journal, 18(2), 0247.

Schuette, V., Embgenbroich, M., Ulas, T., Welz, M., Schulte-Schrepping, J., Draffehn, A. M., Quast, T., Koch, K., Nehring, M., König, J., Zweynert, A., Harms, F. L., Steiner, N., Limmer, A., Förster, I., Berberich-Siebelt, F., Knolle, P. A., Wohlleber, D., Kolanus, W., … Burgdorf, S. (2016). Mannose receptor induces T-cell tolerance via inhibition of CD45 and up-regulation of CTLA-4. Proceedings of the National Academy of Sciences, 113(38), 10649–10654.

Shaaban, S., & Hakim, A. (2019). Vitamin D level in rheumatoid arthritis and its correlation with the disease activity. Journal of Medicine in Scientific Research, 2(2), 152.

Shoelson, S. E., Herrero, L., & Naaz, A. (2007). Obesity, inflammation, and insulin resistance. Gastroenterology, 132(6), 2169–2180.

Stanford, S. M., Rapini, N., & Bottini, N. (2012). Regulation of TCR signalling by tyrosine phosphatases: From immune homeostasis to autoimmunity. Immunology, 137(1), 1–19.

Stranger, B. E., Nica, A. C., Forrest, M. S., Dimas, A., Bird, C. P., Beazley, C., Ingle, C. E., Dunning, M., Flicek, P., Koller, D., Montgomery, S., Tavaré, S., Deloukas, P., & Dermitzakis, E. T. (2007). Population genomics of human gene expression. Nature Genetics, 39(10), 1217–1224.

Published
2025-10-31
How to Cite
Kamel, A. H., Abbas, A. A., & Alosami, M. H. (2025). Diagnostic and predictive relevance of protein tyrosine phosphatase receptor type C serum levels and rs10919563 variant in rheumatoid arthritis and tumor necrosis factor inhibitor outcomes. Regulatory Mechanisms in Biosystems, 16(3), e25121. https://doi.org/10.15421/0225121