Na-AIP-1 secreted by human hookworms suppresses collagen-induced arthritis

Langdon, Kane, Buitrago, Geraldine, Pickering, Darren, Giacomin, Paul, Loukas, Alex, and Haleagrahara, Nagaraja (2022) Na-AIP-1 secreted by human hookworms suppresses collagen-induced arthritis. Inflammopharmacology, 30 (2). pp. 527-535.

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Proteins from helminths have been posed as new immunomodulatory agents with exciting potential in the treatment of immune-mediated diseases including rheumatoid arthritis (RA). In this study we assess the effects of a helminthic excretory/secretory (ES) protein Na-AIP-1 as monotherapy and in combination with methotrexate (MTX) in the well-described collagen-induced arthritis (CIA) model of RA. CIA was induced in DBA/1 J mice which were treated after the onset of arthritis with Na-AIP-1 monotherapy, MTX or Na-AIP-1 + MTX. The clinical scores for weight, arthritis and paw width were recorded along with joint histology as outcome measures. For the clinical parameters of weight, paw score and paw width, none of the Na-AIP-1 monotherapy, MTX therapy or Na-AIP-1 + MTX combination therapy groups displayed any significant difference when compared to the arthritis control. However, a significant reduction in histological score was identified after both monotherapy (Na-AIP-1: 0.83 ± 0.24 vs Arthritis control: 5.58 ± 1.49, p = 0.0277) and combination therapy (Na-AIP-1 + MTX: 0.55 ± 0.28 vs Arthritis control: 5.58 ± 1.49, p = 0.0233) when compared to arthritis control. Furthermore, Na-AIP-1 as both monotherapy (Na-AIP-1: 0.83 ± 0.24 vs MTX: 5.73 ± 1.82 p = 0.0261) and combination therapy (Na-AIP-1 + MTX: 0.55 ± 0.28 vs MTX: 5.73 ± 1.82, p = 0.0221) also significantly reduced histological score when compared to MTX monotherapy. Na-AIP-1 significantly reduced joint pathology in CIA. The hookworm protein Na-AIP-1 seems to be effective in the treatment of RA as monotherapy and when dosed together with MTX, constituting a potential new candidate for drug development. Research should focus on elucidating the mechanism of Na-AIP-1 action as a means to identify novel targets for therapeutics and to further our current understanding of immunobiology in RA.

Item ID: 74570
Item Type: Article (Research - C1)
ISSN: 1568-5608
Keywords: CIA, Collagen-induced arthritis, Helminths, Methotrexate, Na-AIP-1, Rheumatoid Arthritis
Copyright Information: © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC senior principal research fellowship APP1117504, NHMRC program grant APP1132975
Date Deposited: 16 Nov 2022 04:26
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320402 Applied immunology (incl. antibody engineering, xenotransplantation and t-cell therapies) @ 100%
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