Correlation between Serum Levels of Factor I, CD59, Interferon-gamma, and Interleukin-6 with the Response to Rituximab in Iraqi Patients with Rheumatoid Arthritis

Haider Mohammed Hussein; Ali Abdulhussain  Kasim

doi:10.54133/ajms.v7i1(Special).913

Authors

Haider Mohammed Hussein Department of Clinical Laboratory Sciences, College of Pharmacy, University of Baghdad, Baghdad, Iraq https://orcid.org/0009-0009-0294-7007
Ali Abdulhussain Kasim Department of Clinical Laboratory Sciences, College Of Pharmacy, University of Baghdad, Baghdad, Iraq https://orcid.org/0000-0003-0674-0969

DOI:

https://doi.org/10.54133/ajms.v7i1(Special).913

Keywords:

CD59, Factor I, Factor H, Rheumatoid arthritis, Rituxumab

Abstract

Background: Rituximab is a chimeric IgG1 kappa immunoglobulin that has been genetically modified to incorporate human constant region sequences together with murine light- and heavy-chain variable region sequences. People use it to treat rheumatoid arthritis and certain malignancies. Objective: The study aimed to assess the potential association between the serum levels of Factor I, CD59, interleukins (IL)-6, and interferon-gamma (IFN)-γ and the response to Rituximab treatment in Iraqi rheumatoid arthritis patients. Methods: A cross-sectional study was conducted at the rheumatology center at Baghdad Teaching Hospital. Ninety adult patients who have been diagnosed with rheumatoid arthritis and are receiving Rituximab intravenous infusions were included. The enrolled patients were divided into a responder group (45 patients) and a non-responder group (45 patients). The response to Rituximab was assessed according to the 28-joint Disease Activity Score (DAS28). Results: The serum levels of Factor I and CD59 were significantly higher in the non-responders group in comparison to the responders group. In addition, the serum IL-6 and IFN-γ levels were significantly elevated in the non-responders group in comparison to the responders group. The estimated marker serum levels showed a strong, significant correlation with the 6-month change in DAS28. Conclusions: In Rituximab nonresponder RA patients, serum levels of Factor I, CD59, Factor H, IL-6, and IFN-γ are higher, and they have good potential to be used in the assessment of the response to Rituximab therapy.

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References

Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res. 2018;6:15. doi: 10.1038/s41413-018-0016-9.

Kłodziński Ł, Wisłowska M. Comorbidities in rheumatic arthritis. Reumatologia. 2018;56(4):228-233. doi: 10.5114/reum.2018.77974.

Scherer HU, Häupl T, Burmester GR. The etiology of rheumatoid arthritis. J Autoimmun. 2020;110:102400. doi: 10.1016/j.jaut.2019.102400.

Kato E, Sawada T, Tahara K, Hayashi H, Tago M, et al. The age at onset of rheumatoid arthritis is increasing in Japan: a nationwide database study. Int J Rheum Dis. 2017;20(7):839-845. doi: 10.1111/1756-185X.1299.

Calabresi E, Petrelli F, Bonifacio AF, Puxeddu I, Alunno A. One year in review 2018: pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol. 2018;36(2):175-184. PMID: 29716677.

Oldenburg P. Rituximab. Reference Module in Biomedical Sciences: Elsevier; 2018. doi: 10.1016/B978-0-12-801238-3.97945-5.

Atkinson JP, Du Clos TW, Mold C, Kulkarni H, Hourcade D, Wu X. The human complement system: Basic concepts and clinical relevance. Clinical Immunol. 2019:299-317. 10.1016/B978-0-7020-6896-6.00021-1.

Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nature Immunol. 2010;11(9):785-797. doi: 10.1038/ni.1923.

De Boer EC, Van Mourik AG, Jongerius I. Therapeutic lessons to be learned from the role of complement regulators as double-edged sword in health and disease. Front Immunol. 2020;11:578069. doi: 10.3389/fimmu.2020.578069.

Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Ann Rev Immunol. 1996;14(1):397-440. doi: 10.1146/annurev.immunol.14.1.397.

Kondo N, Kuroda T, Kobayashi D. Cytokine networks in the pathogenesis of rheumatoid arthritis. Int J Mol Sci. 2021;22(20). doi: 10.3390/ijms222010922.

Vencovsky J, Ruperto N. 2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Juvenile Dermatomyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Ann Rheum Dis. 2017;76(5):782-791. doi: 10.1136/annrheumdis-2017-211401.

Shrader J, Popovich J, Gracey G, Danoff J. Navicular drop measurement in people with rheumatoid arthritis: Interrater and intrarater reliability. Physical Ther. 2005;85:656-664. doi: 10.1093/ptj/85.7.656.

Vander Cruyssen B, Van Looy S, Wyns B, Westhovens R, Durez P, et al. DAS28 best reflects the physician's clinical judgment of response to infliximab therapy in rheumatoid arthritis patients: validation of the DAS28 score in patients under infliximab treatment. Arthritis ResTher. 2005;7:1-9. doi: 10.1186/ar1787.

Narvaez J, Díaz-Torné C, Ruiz JM, Hernandez MV, Torrente-Segarra V, et al. Predictors of response to rituximab in patients with active rheumatoid arthritis and inadequate response to anti-TNF agents or traditional DMARDs. Clin Exp Rheumatol-Incl Suppl. 2011;29(6):991.

Demoruelle MK, Deane K. Antibodies to citrullinated protein antigens (ACPAs): clinical and pathophysiologic significance. Curr Rheumatol Rep. 2011;13(5):421-430. doi: 10.1007/s11926-011-0193-7.

Volkov M, van Schie KA, van der Woude D. Autoantibodies and B cells: The ABC of rheumatoid arthritis pathophysiology. Immunol Rev. 2020;294(1):148-163. doi: 10.1111/imr.12829.

Kurowska W, Kuca-Warnawin EH, Radzikowska A, Maśliński W. The role of anti-citrullinated protein antibodies (ACPA) in the pathogenesis of rheumatoid arthritis. Cent Eur J Immunol. 2017;42(4):390-398. doi: 10.5114/ceji.2017.72807.

Brink M, Hansson M, Mathsson L, Jakobsson PJ, Holmdahl R, et al. Multiplex analyses of antibodies against citrullinated peptides in individuals prior to development of rheumatoid arthritis. Arthritis Rheum. 2013;65(4):899-910. doi: 10.1002/art.37835.

Van De Stadt LA, Witte BI, Bos WH, Van Schaardenburg D. A prediction rule for the development of arthritis in seropositive arthralgia patients. Ann Rheum Dis. 2012;2012. doi: 10.1136/annrheumdis-2012-202127.

de Hair MJH, Landewé RBM, van de Sande MGH, van Schaardenburg D, van Baarsen LGM, et al. Smoking and overweight determine the likelihood of developing rheumatoid arthritis. Ann Rheum Dis. 2012;2012. doi: 10.1136/annrheumdis-2012-202254.

Scher JU, Bretz WA, Abramson SB. Periodontal disease and subgingival microbiota as contributors for RA pathogenesis: modifiable risk factors? Current Opin Rheumatol. 2014;26(4):424. doi: 10.1097/BOR.0000000000000076.

Willemze A, Trouw LA, Toes REM, Huizinga TWJ. The influence of ACPA status and characteristics on the course of RA. Nature Rev Rheumatol. 2012;8(3):144-152. doi: 10.1038/nrrheum.2011.204.

Amara K, Steen J, Murray F, Morbach H, Fernandez-Rodriguez BM, et al. Monoclonal IgG antibodies generated from joint-derived B cells of RA patients have a strong bias toward citrullinated autoantigen recognition. J Exp Med. 2013;210(3):445-455. doi: 10.1084/jem.20121486.

Ghossan R, Al Tabaa O, Combier A, Steelandt A, Thomas M, et al. Should complete B cell depletion be maintained in patients treated long-term with rituximab for rheumatoid arthritis? Rheumatology. 2023. doi: 10.1093/rheumatology/kead528.

Hornum L, Hansen AJ, Tornehave D, Fjording MS, Colmenero P, et al. C5a and C5aR are elevated in joints of rheumatoid and psoriatic arthritis patients, and C5aR blockade attenuates leukocyte migration to synovial fluid. PloS one. 2017;12(12):e0189017. doi: 10.1371/journal.pone.0189017.

Bemis EA, Norris JM, Seifert J, Frazer-Abel A, Okamoto Y, et al. Complement and its environmental determinants in the progression of human rheumatoid arthritis. Mol Immunol. 2019;112:256-265. doi: 10.1016/j.molimm.2019.05.012.

Toes R, Pisetsky DS. Pathogenic effector functions of AcpA: where do we stand? Ann Rheum Dis. 2019;0(0):2019. doi: 10.1136/annrheumdis-2019-215337.

Anquetil F, Clavel C, Offer G, Serre G, Sebbag M. IgM and IgA rheumatoid factors purified from rheumatoid arthritis sera boost the Fc receptor-and complement-dependent effector functions of the disease-specific anti-citrullinated protein autoantibodies. J Immunol. 2015;194(8):3664-3674. doi: 10.4049/jimmunol.1402334.

Hu W, Ge X, You T, Xu T, Zhang J, et al. Human CD59 inhibitor sensitizes rituximab-resistant lymphoma cells to complement-mediated cytolysis. Cancer Res. 2011;71(6):2298-2307. doi: 10.1158/0008-5472.CAN-10-3016.

Ge X, Du Y, Chen J, Zhu N, Yao J, et al. Herbal NF-κB inhibitors sensitize rituximab-resistant b lymphoma cells to complement-mediated cytolysis. Front Oncol. 2021;11:751904. doi: 10.3389/fonc.2021.751904.

Barahona Correa JE, Franco Cortés MA, Ángel Uribe J, Rodríguez Camacho LS. Comparison of plasma cytokine levels before and after treatment with rituximab in patients with rheumatoid arthritis and systemic lupus erythematosus-associated polyautoimmunity. Universitas Médica. 2018;59(3):21-36. doi: 10.11144/Javeriana.umed59-3.cyto.

Choy EH, De Benedetti F, Takeuchi T, Hashizume M, John MR, et al. Translating IL-6 biology into effective treatments. Nature Reviews Rheumatology. 2020;16(6):335-45. doi.org/10.1038/s41584-020-0419-z

Makuch S, Więcek K, Woźniak M. The immunomodulatory and anti-inflammatory effect of curcumin on immune cell populations, cytokines, and in vivo models of rheumatoid arthritis. Pharmaceuticals. 2021;14(4):309. doi: 10.3390/ph14040309.

Yokoyama Y, Iwasaki T, Kitano S, Satake A, Nomura S, et al. IL-2-anti-L-2 monoclonal antibody immune complexes inhibit collagen-induced arthritis by augmenting regulatory T cell functions. J Immunol. 2018;201(7):1899-1906. doi: 10.4049/jimmunol.1701502.