Effect of active immunization with IL-17A on B cell function and infection risk in pristane-induced lupus model

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Kusworini Handono, Mirza Zaka Pratama, Dita Kartika Sari, Hanestya Oky Hermawan, Hafishtyawan Maulidyananta Agdana, Keryasta Becik Kawuningan, Nafisah Nur'aini, Dian Hasanah, Handono Kalim

2018 International Journal of Rheumatic Diseases Vol. 21 Issue 6 Article Cited by 4 Quartile

Abstract

Purpose: The aim of this study was to determine the effect of active immunization of interleukin (IL)-17A to inhibit B cell functions and monitor the risk of infection in a pristane-induced lupus mice model. Methods: Female Balb/c mice were given a single intraperitoneal injection of 0.5 mL pristane. IL-17A was coupled to keyhole limpet hemocyanin (KLH) and given to mice in three different doses: D0 (0 μg/mL), D1 (1 μg/mL), and D2 (10 μg/mL). The vaccine was given three times with 3-week intervals. At day 42, mice were injected intraperitoneally with methicillin-resistant Staphylococcus aureus (MRSA) and monitored for 3 weeks. Plasma cells proliferation, Th17 and plasma cell percentages were measured by flow cytometry; anti-IL-17A antibody titers, IL-17A, and anti-double-stranded DNA (anti-dsDNA) levels were measured by enzyme-linked immunosorbent assay; and MRSA colonization was measured by bacterial counter. Results: Anti-IL-17A antibody titers were significantly higher in D2 compared to D0 (P = 0.012). Serum IL-17A levels were also significantly lower in D2 compared to D0 (P = 0.000) while Th17 percentages were not significantly different between groups. D2 was also had significantly lower anti-dsDNA (P = 0.021), lower plasma cell percentages (P = 0.000) and lower B cell proliferation rate (P = 0.001) compared to D0. Analysis for the risk of infection also revealed that D2 did not increase the risk of infection compared to D0 (P = 0.504). Conclusion: Active immunization with IL-17A coupled to KLH was able to induce a high titer of neutralizing antibodies against IL-17A and inhibit B cell functions without increasing the risk of infection in a pristane-induced lupus mice model. © 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd

Affiliations

Department of Clinical Pathology, Universitas Brawijaya, Malang, Indonesia; Rheumatology and Immunology Division, Department of Internal Medicine, Universitas Brawijaya, Malang, Indonesia; Master Degrees of Biomedical Sciences, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia