Circulating levels of Interferon regulatory Factor-5 correlates with disease activity in Systemic Lupus Erythematosus Iraqi patients
DOI:
https://doi.org/10.22317/jcms.v8i6.1299Keywords:
IRF5 protein, Lupus Erythematosus, Systemic, Iraqi patientsAbstract
Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a diversity of the phenotypes among the patients. SLE is still one of the great challenges due to the lacking of specific biomarkers for diagnosis, assessing disease activity, and prediction of response to therapy. This study aimed to investigate the role of circulating levels of IRF5 protein in sample of SLE Iraqi patients and its correlation with disease activity, to identify a potential immunological biomarker to mirror disease activity.
Methods: Blood samples were taken from 59 participants diagnosed with SLE cases classified according to the American College of Rheumatology (ACR) criteria. They were scored through the SLE disease activity index 2000 (SLEDAI-2K) to estimate the disease activity, and according to it they were subdivided into “SLE-1 group” (SLEDAI-2k ≤5), and “SLE-2 group” (SLEDAI-2k >5), as well as age and gender matched healthy control group. Circulating levels of IRF5 protein were measured in sera samples by ELISA method.
Results: Our result revealed that the circulating levels of IRF5 protein were significantly higher in the SLE-2 group rather than control group (p<0.01), while there was a non-significant difference between SLE-1 group and control group (p>0.05), as well as between both SLE patient groups. Moreover, the circulating IRF5 protein levels were found to be correlated positively and significantly with disease activity index in both SLE patient groups. The correlation between the circulating levels of IRF5 protein with other parameters revealed that a significant positive correlation was found in SLE-1 group with ESR and globulins, and negative correlation with Hb and (albumin/ globulin) ratio, while in SLE-2 group were positively correlated with urea, creatinine, and uric acid. The analysis of receiver operator curves (ROC) for circulating levels of IRF5 protein in SLE-1 and SLE-2 groups showed a good accuracy to distinguish SLE patients from healthy individuals (AUC=0.758, sensitivity=65.5%, and specificity=69%,), and (AUC=0.788, sensitivity=77.3%, and specificity=72.0%,), respectively.
Conclusions: The circulating levels of IRF5 protein correlate with disease activity in SLE patients reflects the possibility of using it as a potential immunological biomarker for diagnosis, and monitoring the disease activity.
References
La Paglia, G.M.C., Leone, M.C., Lepri, G., Vagelli, R., Valentini, E., Alunno, A. and Tani, C., 2017. One year in review 2017: systemic lupus erythematosus. Clin Exp Rheumatol, 35(4), pp.551-561.
Idborg, H. and Oke, V., 2021. Cytokines as biomarkers in systemic Lupus Erythematosus: Value for diagnosis and drug therapy. International Journal of Molecular Sciences, 22(21), p.11327.
Abdulridha, R.H., Saud, A.M. and Alosami, M.H., 2022. Evaluation of Interferon Alpha (IFN-α) in Women with Systemic Lupus Erythematosus in Iraq. Iraqi Journal of Science, pp.4225-4233.
Hellquist, A., Järvinen, T.M., Koskenmies, S., Zucchelli, M., Orsmark-Pietras, C., Berglind, L., Panelius, J., Hasan, T., Julkunen, H., D’AMATO, M.A.U.R.O. and Saarialho-Kere, U., 2009. Evidence for genetic association and interaction between the TYK2 and IRF5 genes in systemic lupus erythematosus. The Journal of Rheumatology, 36(8), pp.1631-1638.
Trentin, F., Zucchi, D., Signorini, V., Elefante, E., Bortoluzzi, A. and Tani, C., 2021. One year in review 2021: systemic lupus erythematosus. Clin Exp Rheumatol, 39(2), pp.231-241.
Hiba S. Ahmed, Hind S. Ahmed, Ali Ad’hiah, 2020. Interleukin-1 single nucleotide polymorphisms and risk of systemic lupus erythematosus among Iraqi patients. Meta Gene 23 (100640).
Quan, W., An, J., Li, G., Qian, G., Jin, M., Feng, C., Li, S., Li, X., Xu, Y. and Hu, X., 2021. Th cytokine profile in childhood-onset systemic lupus erythematosus. BMC pediatrics, 21(1), pp.1-10.
Katsuyama, T., Tsokos, G.C. and Moulton, V.R., 2018. Aberrant T cell signaling and subsets in systemic lupus erythematosus. Frontiers in immunology, 9, p.1088.
Jasem, M.A., 2007. Hyperprolactenemia in Women with Systemic Lupus Erythematusus. Baghdad Science Journal, 4(4).
Urrego, T., Ortiz-Reyes, B., Vanegas-García, A.L., Muñoz, C.H., González, L.A., Vásquez, G. and Gómez-Puerta, J.A., 2020. Transferrina y ceruloplasmina en orina de pacientes con lupus eritematoso sistemico.? Son utiles para diferenciar pacientes con nefritis lupica? Reumatología Clínica, 16(1), pp.17-23.
Tselios, K., Gladman, D.D., Touma, Z., Su, J., Anderson, N. and Urowitz, M.B., 2019. Disease course patterns in systemic lupus erythematosus. Lupus, 28(1), pp.114-122.
Liu, C.C., Kao, A.H., Manzi, S. and Ahearn, J.M., 2013. Biomarkers in systemic lupus erythematosus: challenges and prospects for the future. Therapeutic advances in musculoskeletal disease, 5(4), pp.210-233.
Capecchi, R., Puxeddu, I., Pratesi, F. and Migliorini, P., 2020. New biomarkers in SLE: from bench to bedside. Rheumatology, 59(Supplement_5), pp. v12-v18.
Rekvig, O.P., 2018. Systemic lupus erythematosus: definitions, contexts, conflicts, enigmas. Frontiers in Immunology, 9, p.387.
Mancl, M.E., Hu, G., Sangster-Guity, N., Olshalsky, S.L., Hoops, K., Fitzgerald-Bocarsly, P., Pitha, P.M., Pinder, K. and Barnes, B.J., 2005. Two discrete promoters regulate the alternatively spliced human interferon regulatory factor-5 isoforms: multiple isoforms with distinct cell type-specific expression, localization, regulation, and function. Journal of Biological Chemistry, 280(22), pp.21078-21090.
Cevik, O., Li, D., Baljinnyam, E., Manvar, D., Pimenta, E.M., Waris, G., Barnes, B.J. and Kaushik-Basu, N., 2017. Interferon regulatory factor 5 (IRF5) suppresses hepatitis C virus (HCV) replication and HCV-associated hepatocellular carcinoma. Journal of Biological Chemistry, 292(52), pp.21676-21689.
Wang, M., Lim, K.H. and Chow, K.T., 2019. Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization. JoVE (Journal of Visualized Experiments), (152), p.e60393.
Banga, J., Srinivasan, D., Sun, C.C., Thompson, C.D., Milletti, F., Huang, K.S., Hamilton, S., Song, S., Hoffman, A.F., Qin, Y.G. and Matta, B., 2020. Inhibition of IRF5 cellular activity with cell-penetrating peptides that target homodimerization. Science advances, 6(20), p. eaay1057.
Ebrahimiyan, H., Bagheri-Hosseinabadi, Z. and Abbasifard, M., 2021. Interferon regulatory factor 5 in Rheumatoid arthritis and systemic lupus erythematosus. Rheumatology Research, 6(1), pp.1-13.
Li, D., Matta, B., Song, S., Nelson, V., Diggins, K., Simpfendorfer, K.R., Gregersen, P.K., Linsley, P. and Barnes, B.J., 2020. IRF5 genetic risk variants drive myeloid-specific IRF5 hyperactivation and presymptomatic SLE. JCI insight, 5(2).
Wang, X., Guo, J., Wang, Y., Xiao, Y., Wang, L. and Hua, S., 2018. Expression levels of interferon regulatory factor 5 (IRF5) and related inflammatory cytokines associated with severity, prognosis, and causative pathogen in patients with community-acquired pneumonia. Medical science monitor: international medical journal of experimental and clinical research, 24, p.3620.
Idborg, H., Zandian, A., Ossipova, E., Wigren, E., Preger, C., Mobarrez, F., Checa, A., Sohrabian, A., Pucholt, P., Sandling, J.K. and Fernandes-Cerqueira, C., 2019. Circulating levels of interferon regulatory factor-5 associates with subgroups of systemic lupus erythematosus patients. Frontiers in immunology, 10, p.1029.
Hochberg, M.C., 1997. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis and rheumatism, 40(9), pp.1725-1725.
Gladman, D.D., Ibanez, D. and Urowitz, M.B., 2002. Systemic lupus erythematosus disease activity index 2000. The Journal of rheumatology, 29(2), pp.288-291.
Zainab M. Dahham, Namir I. A. Haddad, Correlation Between Gene Expression of Interferon Regulatory Factor-5 and Disease Activity Index in Systemic Lupus Erythematosus Iraqi Patients. Iraqi Journal of Science (under publication).
Radisky, D.C., Stallings-Mann, M., Hirai, Y. and Bissell, M.J., 2009. Single proteins might have dual but related functions in intracellular and extracellular microenvironments. Nature Reviews Molecular Cell Biology, 10(3), pp.228-234.
Raghavan, S., Manzanillo, P., Chan, K., Dovey, C. and Cox, J.S., 2008. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature, 454(7205), pp.717-721.
Lomnytska, M., Dubrovska, A., Hellman, U., Volodko, N. and Souchelnytskyi, S., 2006. Increased expression of cSHMT, Tbx3 and utrophin in plasma of ovarian and breast cancer patients. International journal of cancer, 118(2), pp.412-421.
Feng, D., Stone, R.C., Eloranta, M.L., Sangster‐Guity, N., Nordmark, G., Sigurdsson, S., Wang, C., Alm, G., Syvänen, A.C., Rönnblom, L. and Barnes, B.J., Genetic variants and disease‐associated factors contribute to enhanced interferon regulatory factor 5 expression in blood cells of patients with systemic lupus erythematosus,”Arthritis & Rheumatism: Official Journal of the American College of Rheumatology, vol.62, no.2 pp.562-573, 2010.
Jefferies, C.A., 2019. Regulating IRFs in IFN driven disease. Frontiers in immunology, 10, p.325.
Sasidharan, P.K., Bindya, M. and Sajeeth Kumar, K.G., 2012. Hematological manifestations of SLE at initial presentation: is it underestimated? International Scholarly Research Notices, 2012.
Newman, K., Owlia, M.B., El-Hemaidi, I. and Akhtari, M., 2013. Management of immune cytopenias in patients with systemic lupus erythematosus—old and new. Autoimmunity reviews, 12(7), pp.784-791.
Ismail Zoair, M., Zaki El-Ghannam, M., Gaber, A.E.A. and Mohammed Soliman, A., 2021. ASSESSMENT THE ROLE OF URINE OSTEOPROTEGERIN AS A BIOMARKER IN LUPUS NEPHRITIS. Al-Azhar Medical Journal, 50(3), pp.2201-2212.
Majeed, W.A., Jasim, H.M., Farhan, A.A., Ali, A.S. and Gorial, F.I., 2017. Detection of Hematological Biomarkers Associated with Lupus Nephritis in a sample of Iraqi Patients. Journal of Biotechnology Research Center, 11(2).
Baum, C.G., Chiorazzi, N., Frankel, S. and Shepherd, G.M., 1989. Conversion of systemic lupus erythematosus to common variable hypogammaglobulinemia. The American journal of medicine, 87(4), pp.449-456.
Kwon, O.C., Lee, J.S., Ghang, B., Kim, Y.G., Lee, C.K., Yoo, B. and Hong, S., 2018, December. Predicting eventual development of lupus nephritis at the time of diagnosis of systemic lupus erythematosus. In Seminars in arthritis and rheumatism (Vol. 48, No. 3, pp. 462-466). WB Saunders.
Nazri, S.K.S., Wong, K.K. and Hamid, W.Z.W., 2018. Pediatric systemic lupus erythematosus: Retrospective analysis of clinico-laboratory parameters and their association with Systemic Lupus Erythematosus Disease Activity Index score. Saudi medical journal, 39(6), p.627.
Al-Sarray, Z.A., Al-Rayahi, I.A., Al-Hafidh, A.H. and Dwayyikh, A.T., 2020. Serum Protein Electrophoresis in Iraqi Systemic lupus Erythematous Patient. Al-Nisour Journal for Medical Sciences, 2(1).
Yip, J., Aghdassi, E., Su, J., Lou, W., Reich, H., Bargman, J., Scholey, J., Gladman, D.D., Urowitz, M.B. and Fortin, P.R., 2010. Serum albumin as a marker for disease activity in patients with systemic lupus erythematosus. The Journal of rheumatology, 37(8), pp.1667-1672.
Cojocaru, M., Cojocaru, M.I., Silosi, I. and Vrabie, D.C., 2010. Kidney damage in autoimmune diseases. Journal of Medical Biochemistry, 29(2), pp.61-65.
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