Trends in Immunotherapy

Article

ANA Serum in a Non-Human Primate (Macaca fascicularis) Model of Systemic Lupus Erythematosus Induced by Pristane

Downloads

https://doi.org/10.54963/ti.v10i1.1672
Jonny, J., Zenia, P., Kusumastuti, S., Wirjopranoto, S., Nidom, C. A., Sudiana, I. K., Pratiwi, E. D., Mawaddah, T. W., Nidom, A. N., Nidom, R. V., Indrasari, S., & Rosytania, I. Y. (2026). ANA Serum in a Non-Human Primate (Macaca fascicularis) Model of Systemic Lupus Erythematosus Induced by Pristane. Trends in Immunotherapy, 10(1), 144–154. https://doi.org/10.54963/ti.v10i1.1672
Volume 10, Issue 1 (2026)
Copyright (c) 2026 Jonny Jonny, Pepita Zenia, Sanindita Kusumastuti, Soetojo Wirjopranoto, Chairul Anwar Nidom, I Ketut Sudiana, Elisa Diah Pratiwi, Tiza Wuri Mawaddah, Astria Novitasari Nidom, Reviany Vibrianita Nidom, Setyarina Indrasari, Irma Yurita Rosytania
Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright

The authors shall retain the copyright of their work but allow the Publisher to publish, copy, distribute, and convey the work.

License

Trends in Immunotherapy (TI)  publishes accepted manuscripts under Creative Commons Attribution 4.0 International (CC BY 4.0). Authors who submit their papers for publication by TI agree to have the CC BY 4.0 license applied to their work, and that anyone is allowed to reuse the article or part of it free of charge for any purpose, including commercial use. As long as the author and original source are properly cited, anyone may copy, redistribute, reuse, and transform the content.

Authors

  • Jonny Jonny

    Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia
    Indonesia Army Cell Cure Center, Gatot Soebroto Central Army Hospital, Jakarta 10410, Indonesia
    Faculty of Military Medicine, Indonesia Defense University, Bogor 16810, Indonesia
  • Pepita Zenia

    Indonesia Army Cell Cure Center, Gatot Soebroto Central Army Hospital, Jakarta 10410, Indonesia
  • Sanindita Kusumastuti

    Indonesia Army Cell Cure Center, Gatot Soebroto Central Army Hospital, Jakarta 10410, Indonesia
  • Soetojo Wirjopranoto

    Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia
  • Chairul Anwar Nidom

    Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia
    Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya 60115, Indonesia
    Department of Research and Development Laboratory, Professor Nidom Foundation, Surabaya 60236, Indonesia
    Global Biosains Teknologi, Malang 65145, Indonesia
  • I Ketut Sudiana

    Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia
  • Elisa Diah Pratiwi

    Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya 60115, Indonesia
    Department of Research and Development Laboratory, Professor Nidom Foundation, Surabaya 60236, Indonesia
  • Tiza Wuri Mawaddah

    Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya 60115, Indonesia
    Department of Research and Development Laboratory, Professor Nidom Foundation, Surabaya 60236, Indonesia
  • Astria Novitasari Nidom

    Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia
    Department of Research and Development Laboratory, Professor Nidom Foundation, Surabaya 60236, Indonesia
  • Reviany Vibrianita Nidom

    Department of Research and Development Laboratory, Professor Nidom Foundation, Surabaya 60236, Indonesia
  • Setyarina Indrasari

    Department of Research and Development Laboratory, Professor Nidom Foundation, Surabaya 60236, Indonesia
  • Irma Yurita Rosytania

    Department of Research and Development Laboratory, Professor Nidom Foundation, Surabaya 60236, Indonesia

Received: 30 September 2025; Revised: 17 November 2025; Accepted: 1 December 2025; Published: 9 February 2026

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by the production of antinuclear antibodies (ANA). While murine models are widely used for lupus research, their translational value is limited by physiological differences. Macaca fascicularis, a non-human primate, offers a closer model due to its genetic and immunological similarities to humans. Pristane (2,6,10,14-tetramethylpentadecane), a hydrocarbon oil, can induce lupus-like manifestations, including ANA production, but evidence in Macaca fascicularis remains scarce. This study assessed ANA titers following pristane induction in seven macaques, with one serving as a negative control. A single intraperitoneal dose of pristane (5 mL/kg) was administered, and ANA titers were evaluated biweekly using ELISA. ANA seropositivity (titer ≥1:80) was first detected at week 4, increasing to four macaques by week 8 and persisting at four positives in week 10. The duration of ANA positivity varied across individuals, ranging from a single week to continuous six-week responses, with one showing a biphasic pattern. The control macaque remained negative throughout. Clinical observations included alopecia, weight loss, lymphopenia, hematuria, and proteinuria in ANA-positive animals. In conclusion, pristane induced measurable autoimmunity in Macaca fascicularis, supporting its utility as a translational model for lupus research and preclinical testing of therapeutic interventions.

Keywords:

Macaca fascicularis Antinuclear Antibody Systemic Lupus Erythematosus Non-Human Primate Model Pristane Autoimmunity Lupus

References

  1. Arneth, B. Systemic Lupus Erythematosus and DNA Degradation and Elimination Defects. Front. Immunol. 2019, 10, 1697. DOI: https://doi.org/10.3389/fimmu.2019.01697
  2. Fatoye, F.; Gebrye, T.; Mbada, C. Global and Regional Prevalence and Incidence of Systemic Lupus Erythematosus in Low-and-Middle Income Countries: A Systematic Review and Meta-Analysis. Rheumatol. Int. 2022, 42, 2097–2107. DOI: https://doi.org/10.1007/s00296-022-05183-4
  3. Tian, J.; Zhang, D.; Yao, X.; et al. Global Epidemiology of Systemic Lupus Erythematosus: A Comprehensive Systematic Analysis and Modelling Study. Ann. Rheum. Dis. 2023, 82, 351–356. DOI: https://doi.org/10.1136/ard-2022-223035
  4. Indonesian Rheumatology Association, 2025. Clinical Guidelines for the Diagnosis and Management of Systemic Lupus Erythematosus. Available online: https://reumatologi.or.id/wp-content/uploads/2025/10/Buku-Lupus-IRA-2025.pdf (accessed on 26 September 2025). (in Indonesian)
  5. Kriswiastiny, R.; Mustofa, F.; Prasetia, T.; et al. Association Between Systemic Lupus Erythematosus (SLE) Disease Activity Based on the Mex SLEDAI Score and Body Mass Index (BMI) in the Lupus Community of Bandar Lampung City. MAHESA Malahayati Health Stud. J. 2022, 2, 278–288. DOI: https://doi.org/10.33024/mahesa.v2i2.3952 (in Indonesian)
  6. Hamijoyo, L.; Sapartini, G.; Rahmadi, A.R.; et al. Comparison of Clinical Presentation and Outcome of Childhood-Onset and Adulthood-Onset of Systemic Lupus Erythematosus among Indonesian Patients. Lupus 2022, 31, 759–764. DOI: https://doi.org/10.1177/09612033221093482
  7. Richard, M.L.; Gilkeson, G. Mouse Models of Lupus: What They Tell Us and What They Don’t. Lupus Sci. Med. 2018, 5, e000199. DOI: https://doi.org/10.1136/lupus-2016-000199
  8. Ignatova, I.E.; Agrba, V.Z.; Karal-Ogly, D.D. Cellular Immunity Standard Values in Macaca fascicularis. Bull. Exp. Biol. Med. 2014, 157, 265–267. DOI: https://doi.org/10.1007/s10517-014-2541-x
  9. Ignatova, I.E.; Agrba, V.Z. Parameters of Cellular Immunity in Primates. Available online: https://www.researchgate.net/publication/49641293_Parameters_of_Cellular_Immunity_in_Primates (accessed on 24 September 2025).
  10. Calvani, N.; Caricchio, R.; Tucci, M.; et al. Induction of Apoptosis by the Hydrocarbon Oil Pristane: Implications for Pristane-Induced Lupus. J. Immunol. 2005, 175, 4777–4782. Available online: https://pubmed.ncbi.nlm.nih.gov/16177126/
  11. Freitas, E.C.; de Oliveira, M.S.; Monticielo, O.A. Pristane-Induced Lupus: Considerations on This Experimental Model. Clin. Rheumatol. 2017, 36, 2403–2414. DOI: https://doi.org/10.1007/s10067-017-3811-6
  12. Chowdhary, V.; Grande, J.; Luthra, H.; et al. Characterization of Haemorrhagic Pulmonary Capillaritis: Another Manifestation of Pristane-Induced Lupus. Rheumatol. 2007, 46, 1405–1410. DOI: https://doi.org/10.1093/rheumatology/kem117
  13. Reeves, W.H.; Lee, P.Y.; Weinstein, J.S.; et al. Induction of Autoimmunity by Pristane and Other Naturally-Occurring Hydrocarbons. Trends Immunol. 2009, 30, 455–464. DOI: https://doi.org/10.1016/j.it.2009.06.003
  14. Pannu, N.; Bhatnagar, A. Oxidative Stress and Immune Complexes: Pathogenic Mechanisms in Pristane-Induced Murine Model of Lupus. Immunobiology 2020, 225, 151871. DOI: https://doi.org/10.1016/j.imbio.2019.11.006
  15. Zhuang, H.; Szeto, C.; Han, S.; et al. Animal Models of Interferon Signature Positive Lupus. Front. Immunol. 2015, 6, 291. DOI: https://doi.org/10.3389/fimmu.2015.00291
  16. dos Santos, M.; Poletti, P.T.; Favero, G.; et al. Protective Effects of Quercetin Treatment in a Pristane-Induced Mouse Model of Lupus Nephritis. Autoimmunity 2018, 51, 69–80. DOI: https://doi.org/10.1080/08916934.2018.1442828
  17. Chuah, J.J.M.; Hertzog, P.J.; Campbell, N.K. Immunoregulation by Type I Interferons in the Peritoneal Cavity. J. Leukoc. Biol. 2022, 111, 337–353. DOI: https://doi.org/10.1002/JLB.3MR0821-147R
  18. Han, S.; Zhuang, H.; Arja, R.D.; et al. A Novel Monocyte Differentiation Pattern in Pristane-Induced Lupus with Diffuse Alveolar Hemorrhage. eLife 2022, 11, e76205. DOI: https://doi.org/10.7554/eLife.76205
  19. Lee, P.; Li, Y.; Kumagai, Y.; et al. Type I Interferon Modulates Monocyte Recruitment and Maturation in Chronic Inflammation. Am. J. Pathol. 2009, 175, 2023–2033. DOI: https://doi.org/10.2353/ajpath.2009.090328
  20. Song, Y.; Li, J.; Wu, Y. Evolving Understanding of Autoimmune Mechanisms and New Therapeutic Strategies of Autoimmune Disorders. Signal Transduct. Target. Ther. 2024, 9, 263. DOI: https://doi.org/10.1038/s41392-024-01952-8
  21. Wang, J.; Shen, H.; Zhu, Y.; et al. Characterization of a PRISTANE-Induced Lupus-Associated Model in the Non-Human Primate Cynomolgus Monkey. J. Med. Primatol. 2018, 47, 18–28. DOI: https://doi.org/10.1111/jmp.12280
  22. Han, S.; Zhuang, H.; Xu, Y.; et al. Maintenance of Autoantibody Production in Pristane-Induced Murine Lupus. Arthritis Res. Ther. 2015, 17, 384. DOI: https://doi.org/10.1186/s13075-015-0886-9
  23. Leiss, H.; Niederreiter, B.; Bandur, T.; et al. Pristane-Induced Lupus as a Model of Human Lupus Arthritis: Evolvement of Autoantibodies, Internal Organ and Joint Inflammation. Lupus 2013, 22, 778–792. DOI: https://doi.org/10.1177/0961203313492869
  24. Sandling, J.K.; Pucholt, P.; Rosenberg, L.H.; et al. Molecular Pathways in Patients with Systemic Lupus Erythematosus Revealed by Gene-Centered DNA Sequencing. Ann. Rheum. Dis. 2021, 80, 109–117. DOI: https://doi.org/10.1136/annrheumdis-2020-218636
  25. Cho, J.; Lahiri, M.; Teoh, L.K.; et al. Predicting Flares in Patients with Stable Systemic Lupus Erythematosus. Semin. Arthritis Rheum. 2019, 49, 91–97. DOI: https://doi.org/10.1016/j.semarthrit.2019.01.001
  26. Langham, J.; Barut, V.; Samnaliev, M.; et al. Disease Severity, Flares and Treatment Patterns in Adults with Systemic Lupus Erythematosus in the UK: A Real-World Observational Retrospective Cohort Analysis. Rheumatol. Adv. Pract. 2021, 5, rkab061. DOI: https://doi.org/10.1093/rap/rkab061
  27. Kim, J.M.; Park, S.H.; Kim, H.Y.; et al. A Plasmacytoid Dendritic Cells-Type I Interferon Axis Is Critically Implicated in the Pathogenesis of Systemic Lupus Erythematosus. Int. J. Mol. Sci. 2015, 16, 14158–14170. DOI: https://doi.org/10.3390/ijms160614158
  28. Simpson, J.; Miles, K.; Trüb, M.; et al. Plasmacytoid Dendritic Cells Respond Directly to Apoptotic Cells by Secreting Immune Regulatory IL-10 or IFN-α. Front. Immunol. 2016, 7. DOI: https://doi.org/10.3389/fimmu.2016.00590
  29. Suvandjieva, V.; Tsacheva, I.; Santos, M.; et al. Modelling the Impact of NETosis During the Initial Stage of Systemic Lupus Erythematosus. Bull. Math. Biol. 2024, 86, 66. DOI: https://doi.org/10.1007/s11538-024-01291-3
  30. Ceccarelli, F.; Natalucci, F.; Olivieri, G.; et al. Development of Systemic Autoimmune Diseases in Healthy Subjects Persistently Positive for Antiphospholipid Antibodies: Long-Term Follow-Up Study. Biomolecules 2022, 12, 1088. DOI: https://doi.org/10.3390/biom12081088
  31. Frazzei, G.; van Vollenhoven, R.F.; de Jong, B.A.; et al. Preclinical Autoimmune Disease: A Comparison of Rheumatoid Arthritis, Systemic Lupus Erythematosus, Multiple Sclerosis and Type 1 Diabetes. Front. Immunol. 2022, 13. DOI: https://doi.org/10.3389/fimmu.2022.899372
  32. Dai, X.; Fan, Y.; Zhao, X. Systemic Lupus Erythematosus: Updated Insights on the Pathogenesis, Diagnosis, Prevention and Therapeutics. Signal Transduct. Target. Ther. 2025, 10, 102. DOI: https://doi.org/10.1038/s41392-025-02168-0
  33. Kim, Y.R.; Jung, Y.; Kang, I.; et al. Understanding Sex Differences in Autoimmune Diseases: Immunologic Mechanisms. Int. J. Mol. Sci. 2025, 26, 7101. DOI: https://doi.org/10.3390/ijms26157101
  34. Vieira, A.A.; Almada-Correia, I.; Inácio, J.; et al. Female-Bias in Systemic Lupus Erythematosus: How Much Is the X Chromosome to Blame? Biol. Sex Differ. 2024, 15, 76. DOI: https://doi.org/10.1186/s13293-024-00650-y
  35. Smith, D.L.; Dong, X.; Du, S.; et al. A Female Preponderance for Chemically Induced Lupus in SJL/J Mice. Clin. Immunol. Orlando Fla. 2007, 122, 101–107. DOI: https://doi.org/10.1016/j.clim.2006.09.009
  36. Dema, B.; Lamri, Y.; Pellefigues, C.; et al. Basophils Contribute to Pristane-Induced Lupus-Like Nephritis Model. Sci. Rep. 2017, 7, 7969. DOI: https://doi.org/10.1038/s41598-017-08516-7
  37. Zhou, Y.; Yang, B.; Long, H.; et al. Immune Cell Alterations in a Pristane-Induced Lupus Model in C57BL/6J Mice. Rheumatol. Autoimmun. 2025, 5, 130–139. DOI: https://doi.org/10.1002/rai2.12164
  38. Stull, C.; Sprow, G.; Werth, V.P. Cutaneous Involvement in Systemic Lupus Erythematosus: A Review for the Rheumatologist. J. Rheumatol. 2023, 50, 27–35. DOI: https://doi.org/10.3899/jrheum.220089
  39. Choi, W.J.; Kim, J.E.; Kang, H. Frequency of Antinuclear Antibody Positivity in Patients with Pattern Hair Loss. Ann. Dermatol. 2015, 27, 210–212. DOI: https://doi.org/10.5021/ad.2015.27.2.210
  40. Ong, M.M.; Singal, A.; Lipner, S.R. Increased Prevalence of Antinuclear Antibody Positivity in Central Centrifugal Cicatricial Alopecia Patients. Skin Appendage Disord. 2025, 11, 385–388. DOI: https://doi.org/10.1159/000543767
  41. Bruera, S.; Chavula, T.; Madan, R.; et al. Targeting Type I Interferons in Systemic Lupus Erythematous. Front. Pharmacol. 2023, 13. DOI: https://doi.org/10.3389/fphar.2022.1046687
  42. Postal, M.; Vivaldo, J.F.; Fernandez-Ruiz, R.; et al. Type I Interferon in the Pathogenesis of Systemic Lupus Erythematosus. Curr. Opin. Immunol. 2020, 67, 87–94. DOI: https://doi.org/10.1016/j.coi.2020.10.014