Relationship Between Disease Activity, Levels of IFN-a, IL-4, IL-6, and Anti-NMDA to Cognitive Dysfunction (MoCA-INA Score) in Systemic Lupus Erythematosus (SLE) Patients with Cognitive Dysfunction

Authors

  • Bantar Suntoko Doctoral study Program of Medical and Health Science, Faculty of Medicine, Diponegoro University, Semarang, Indonesia
  • Suharyo Hadisaputro Division of Tropical Infectious Disease, Department of Internal Medicine, Faculty of Medicine, Diponegoro University - Kariadi Hospital, Semarang, Indonesia
  • Handono Kalim Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Brawijaya University - Saiful Anwar Hospital, Malang, Indonesia
  • Suyanto Hadi Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Diponegoro University - Kariadi Hospital, Semarang, Indonesia
  • Wahyu Adirama Saputra Department of Internal Medicine, Faculty of Medicine, Diponegoro University - Kariadi Hospital, Semarang, Indonesia

Keywords:

Cognitive dysfunction, Systemic Lupus Erythematosus, Disease activity, IFN-a, IL-4, IL-6, Anti-NMDA

Abstract

Background: Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) is a condition that impacts the patients’ brain with SLE, and cognitive dysfunction (CD) is the most common manifestation. Subsequently, the CD hurts the life quality of SLE patients and creates impaired social function. Furthermore, the Montreal Cognitive Assessment (MoCA-INA) is a screening instrument to evaluate cognitive function. In the context of lupus, cytokines, and autoantibodies act as biomarkers in SLE disease control activities. Purpose: The aim of this study was to analyze the correlation between disease activity, IFN-a, IL-4, IL-6 and Anti-NMDA on CD (MoCA-INA Score) in SLE patients with CD. Methods: This analytical observational study was performed with a cross-sectional design and included a sample of 56 SLE patients. The independent variables were the degree of the disease activity, and levels of IFN-a, IL-4, IL-6, and anti-NMDA. The dependent variable consisted of the degree of CD (MoCA-INA score), while the confounding variables were age, DM, gender, hypertension, obesity, and dyslipidemia. Subsequently, the CD was described as a MoCA-INA score <26, and disease activity was estimated based on the SLEDAI score. Results: Increased IL-6 levels were correlated with decreased MoCA-INA scores (p=0.003; r= -0.387). Younger age was found to be associated with more severe CD (p=0.006) Conclusion:In conclusion, IL-6 levels can be used as a predictor severity of CD in SLE patients. 

Author Biography

Bantar Suntoko, Doctoral study Program of Medical and Health Science, Faculty of Medicine, Diponegoro University, Semarang, Indonesia

1Doctoral Study Program of Medical and Health Science, Faculty of Medicine, University of Diponegoro, Semarang Indonesia

References

Netto TM, Zimmermann N, Rueda-Lopes F, Bizzo BC, Fonseca RP, Gasparetto EL. Neuropsychiatric lupus: classification criteria in neuroimaging studies. Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques. 2013;40(3):284–91.

Hanly JG, Urowitz MB, Sanchez-Guerrero J, et al. Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: An international inception cohort study. Arthritis Rheum. 2007;56(1):265–73.

Zhang Y, Han H, Chu L. Neuropsychiatric lupus erythematosus: future directions and challenges; a systematic review and survey. Clinics. 2020;75: e1515.

Smith T, Gildeh N, Holmes C. The montreal cognitive assessment: validity and utility in a memory clinic setting. The Canadian Journal of Psychiatry. 2007;52(5):329–32.

Yap DYH, Lai KN. Cytokines and their roles in the pathogenesis of systemic lupus erythematosus: from basics to recent advances. J Biomed Biotechnol. 2010; 2010:1–10.

Chakravarty EF, Bush TM, Manzi S, Clarke AE, Ward MM. Prevalence of adult systemic lupus erythematosus in California and Pennsylvania in 2000: Estimates obtained using hospitalization data. Arthritis Rheum. 2007;56(6):2092–4.

Boodhoo KD, Liu S, Zuo X. Impact of sex disparities on the clinical manifestations in patients with systemic lupus erythematosus. Medicine. 2016;95(29):e4272.

Weckerle CE, Niewold TB. the unexplained female predominance of systemic lupus erythematosus: clues from genetic and cytokine studies. Clin Rev Allergy Immunol. 2011;40(1):42–9.

Walters E, Rider V, Abdou NI, et al. Estradiol targets T cell signaling pathways in human systemic lupus. Clinical Immunology. 2009;133(3):428–36.

Koelmeyer R, Nim HT, Nikpour M, et al. High disease activity status suggests more severe disease and damage accrual in systemic lupus erythematosus. Lupus Sci Med. 2020;7(1): e000372.

Shamim R, Farman S, Batool S, Anwer Khan SE, Raja MKH. Association of systemic lupus erythematosus disease activity index score with clinical and laboratory parameters in pediatric onset systemic lupus erythematosus. Pak J Med Sci. 2020;36(3).

Rambe AS, Fitri FI. Correlation between the Montreal cognitive assessment-Indonesian version (Moca-INA) and the mini-mental state examination (MMSE) in elderly. Open Access Maced J Med Sci. 2017;5(7):915–9.

Conti F, Alessandri C, Perricone C, et al. Neurocognitive dysfunction in systemic lupus erythematosus: association with antiphospholipid antibodies, disease activity and chronic damage. PLoS One. 2012;7(3): e33824.

Anjalia S, Ong PA, Atik N, Hamijoyo L. Memory performance in patient with systemic lupus erythematosus using moca-ina in hasan sadikin genneral hospital Bandung. Indonesian Journal of Rheumatology. 2018 Feb 9;9(1).

Kowal C, DeGiorgio LA, Lee JY, et al. Human lupus autoantibodies against NMDA receptors mediate cognitive impairment. Proceedings of the National Academy of Sciences. 2006;103(52):19854–9.

Saepudin A, Ong PA, Hidayat S, Rahmadi AR, Hamijoyo L. Correlation between cognitive function with disease activity of systemic lupus erythematosus patients in Dr. Hasan Sadikin Hospital Bandung: An analytical cross-sectional study. Indonesian Journal of Rheumatology. 2019;11(1).

Raghunath S, Glikmann-Johnston Y, Golder V, et al. Clinical associations of cognitive dysfunction in systemic lupus erythematosus. Lupus Sci Med. 2023;10(1): e000835.

Popescu A, H. Kao A. Neuropsychiatric systemic lupus erythematosus. Curr Neuropharmacol. 2011;9(3):449–57.

Ruchakorn N, Ngamjanyaporn P, Suangtamai T, et al. Performance of cytokine models in predicting SLE activity. Arthritis Res Ther. 2019;21(1):287.

Bradburn S, Sarginson J, Murgatroyd CA. Association of peripheral interleukin-6 with global cognitive decline in non-demented adults: A meta-analysis of prospective studies. Front Aging Neurosci. 2018;8:9.

Ohl K, Tenbrock K. Inflammatory cytokines in systemic lupus erythematosus. J Biomed Biotechnol. 2011; 2011:1–14.

Montagne A, Barnes SR, Sweeney MD, et al. Blood-brain barrier breakdown in the aging human hippocampus. Neuron. 2015;85(2):296–302.

Varatharaj A, Galea I. The blood-brain barrier in systemic inflammation. Brain Behav Immun. 2017; 60:1–12.

Marsland AL, Gianaros PJ, Abramowitch SM, Manuck SB, Hariri AR. Interleukin-6 covaries inversely with hippocampal grey matter volume in middle-aged adults. Biol Psychiatry. 2008;64(6):484–90.

Satizabal CL, Zhu YC, Mazoyer B, Dufouil C, Tzourio C. Circulating IL-6 and CRP are associated with MRI findings in the elderly: The 3C-Dijon Study. Neurology. 2012;78(10):720–7.

McCarrey A, Pacheco J, Carlson O, et al. Interleukin-6 is linked to longitudinal rates of cortical thinning in aging. Transl Neurosci. 2014;5(1):1–7.

Niewold TB, Adler JE, Glenn SB, Lehman TJA, Harley JB, Crow MK. Age‐ and sex‐related patterns of serum interferon‐α activity in lupus families. Arthritis Rheum. 2008;58(7):2113–9.

Raghunath S, Glikmann-Johnston Y, Golder V, et al. Clinical associations of cognitive dysfunction in systemic lupus erythematosus. Lupus Sci Med. 2023;10(1): e000835.

Niewold TB, Adler JE, Glenn SB, Lehman TJA, Harley JB, Crow MK. Age‐ and sex‐related patterns of serum interferon‐α activity in lupus families. Arthritis Rheum. 2008;58(7):2113–9.

Downloads

Published

2023-11-01

How to Cite

Suntoko, B., Hadisaputro, S., Kalim, H., Hadi, S., & Saputra, W. A. (2023). Relationship Between Disease Activity, Levels of IFN-a, IL-4, IL-6, and Anti-NMDA to Cognitive Dysfunction (MoCA-INA Score) in Systemic Lupus Erythematosus (SLE) Patients with Cognitive Dysfunction. Acta Medica Indonesiana, 55(3), 307. Retrieved from https://www.actamedindones.org/index.php/ijim/article/view/2475

Issue

Vol. 55 No. 3 (2023): Acta Medica Indonesiana

Section

ORIGINAL ARTICLE

License

Copyright

The authors who publish this journal agree to the following requirements:

  1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
  2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
  3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work. (See The Effect of Open Access)
Privacy Statement

The names and email addresses entered in this journal site will be used exclusively for the stated purposes of this journal and will not be made available for any other purpose or to any other party.