Characterization of chronic relapsing antibody mediated arthritis in mice with a mutation in Ncf1 causing reduced oxidative burst

Peibin Liang; Yanpeng Li; Rui Xu; Kutty Selva Nandakumar; Roma Stawikowska; Gregg B Fields; Rikard Holmdahl

doi:10.1186/s43556-022-00076-1

Characterization of chronic relapsing antibody mediated arthritis in mice with a mutation in Ncf1 causing reduced oxidative burst

Mol Biomed. 2022 May 12;3(1):14. doi: 10.1186/s43556-022-00076-1.

Authors

Peibin Liang¹, Yanpeng Li¹, Rui Xu¹, Kutty Selva Nandakumar¹, Roma Stawikowska², Gregg B Fields², Rikard Holmdahl^{3

4}

Affiliations

¹ Medical Inflammation Research, Pharmacology School, Southern Medical University, Guangzhou, 510515, China.
² Department of Chemistry & Biochemistry and I-HEALTH, Florida Atlantic University, Jupiter, FL, USA.
³ Medical Inflammation Research, Pharmacology School, Southern Medical University, Guangzhou, 510515, China. rikard.holmdahl@ki.se.
⁴ Medical Inflammation Research, Department of Biochemistry and Biophysics, Karolinska Institute, SE-17177, Stockholm, Sweden. rikard.holmdahl@ki.se.

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disorder affecting joints with a hallmark of autoantibody production. Mannan-enhanced collagen type II (COL2) antibody induced arthritis (mCAIA) in neutrophil cytosolic factor 1(Ncf1) mutation mouse is a chronic disease model imitating RA in mice. In this study, we characterize the chronic phase of mCAIA in Ncf1 mutated (BQ.Ncf1^m1j/m1j) mice. Arthritis was induced by an intravenous injection of anti-COL2 monoclonal antibodies on day 0 followed by intra-peritoneal injections of mannan (from Saccharomyces cerevisiae) on days 3 and 65 in BQ.Ncf1 ^m1j/m1j and BQ mice. Bone erosion was analysed by computed tomography (CT) and blood cell phenotypes by flow cytometry. Cytokines and anti-COL2 antibodies were analyzed with multiplex bead-based assays. The arthritis in the Ncf1^m1j/m1j mice developed with a chronic and relapsing disease course, which was followed for 200 days and bone erosions of articular joints were evaluated. An increased number of circulating CD11b⁺ Ly6G⁺ neutrophils were observed during the chronic phase, together with a higher level of G-CSF (granulocyte colony-stimulating factor) and TNF-α. In conclusion, the chronic relapsing arthritis of mCAIA in the Ncf1^m1j/m1j mice develop bone erosions associated with a sustained neutrophil type of inflammatory responses.

Keywords: Anti-COL2 antibody; Chronic phase; Collagen type II induced arthritis; Neutrophil cytosolic factor 1; Rheumatoid arthritis.

Abstract

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