Collagen Type II-Specific Monoclonal Antibody-Induced Arthritis in Mice

Nandakumar, Kutty Selva; Svensson, Lovisa; Holmdahl, Rikard

doi:10.1016/s0002-9440(10)63542-0

Cited by 259 publications

(113 citation statements)

References 61 publications

Supporting

Mentioning

103

Contrasting

Order By: Relevance

“…Interestingly, the mice also develop a joint-specific autoimmune response, as seen with increased levels to CII, in fact to epitopes also recognized in human RA (21). Antibodies to these epitopes (C1, J1, and U1) do in fact induce arthritis upon passive transfer (40).…”

Section: Discussionmentioning

confidence: 90%

Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene

Hultqvist

Olofsson

Holmberg

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

322

372

View full text Add to dashboard Cite

The Ncf1 gene was recently identified as a strong regulator of severe arthritis in rat. This finding was surprising, because the disease-promoting allele mediated a lower level of reactive oxygen species in NADPH oxidase-expressing cells. We have now investigated a splice mutation of the Ncf1 gene in B10.Q mice, causing a truncated and nonfunctional Ncf1 protein. We found that the mutated Ncf1 led to a more severe and chronic relapsing collageninduced arthritis. Enhanced IgG and delayed-type hypersensitivity responses against type II collagen were seen, indicating increased activity of autoreactive T cells. Interestingly, female Ncf1-mutated mice spontaneously developed severe arthritis during the postpartum period. The arthritis was accompanied by an increased antibody response to type II collagen, with the same fine specificity as in collagen-induced arthritis. The enhancing effect of the mutated Ncf1 could also be shown to be more general in that it enhanced myelin oligodendrocyte glycoprotein protein-induced experimental autoimmune encephalomyelitis, a model for multiple sclerosis. These results show that Ncf1, a gene important for oxidative burst, regulates the susceptibility and severity of both arthritis and encephalomyelitis and modulates, directly or indirectly, the level of T cell-dependent autoimmune responses. rodent ͉ T lymphocytes ͉ NADPH

show abstract

Section: Discussionmentioning

confidence: 90%

Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene

Hultqvist

Olofsson

Holmberg

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

322

372

View full text Add to dashboard Cite

show abstract

“…From these findings, we hypothesize that the EPS-dependent reduction of anticollagen antibodies could result in inhibition of the development of CIA in DBA/1 mice. Indeed, there are many studies showing a close link between humoral responses to collagen and disease severity (Marcinkiewicz et al 2007b;Nandakumar et al 2003;Nowak et al 2010;Williams et al 1998). In our experimental set-up, the protective effects of EPS in model 1 of CIA were stronger than in model 2, perhaps because of the very high serum levels of CII-specific antibodies after using CFA as an adjuvant.…”

Section: Discussionmentioning

confidence: 99%

“…Some bacterial components (for example, LPS or mycobacterial components) are commonly used as adjuvants to induce or exacerbate joint inflammation in experimental models of RA, including collagen-induced arthritis (CIA) in mice and rats (Courtenay et al 1980;Williams 2004). A rapid onset of arthritis can be induced by a passive transfer of monoclonal antibodies specific to arthritogenic epitopes of collagen type II (CII) and LPS (Nandakumar et al 2003;Oestergaard et al 2008). Importantly, the severity of arthritis depends on the amount of antibodies injected.…”

Section: Introductionmentioning

confidence: 99%

Lactobacillus rhamnosus Exopolysaccharide Ameliorates Arthritis Induced by the Systemic Injection of Collagen and Lipopolysaccharide in DBA/1 Mice

Nowak

Ciszek-Lenda

Śróttek

et al. 2012

Arch. Immunol. Ther. Exp.

View full text Add to dashboard Cite

Oral administration of some probiotic bacteria (e.g. Lactobacillus rhamnosus) attenuates various types of experimental arthritis, including collagen-induced arthritis (CIA) and inhibits arthritogenic autoantibodies. Much less is known about the possible anti-arthritogenic properties of exopolysaccharide (EPS), the major component of lactic bacteria biofilm. In this study, we asked the question whether systemic administration of EPS derived from L. rhamnosus KL37 depresses the production of anti-collagen IgG and affects the development of CIA in DBA/1 mice. Arthritis was induced employing two models of active CIA, in which mice were immunized with type II collagen (CII) either in the presence of lipopolysaccharide (LPS; mild arthritis with moderate CII-specific IgG production) or with Complete Freund's Adjuvant and LPS (severe arthritis with massive CII-specific IgG production). Passive CIA was induced by intravenous injection of CII-specific monoclonal antibodies and LPS. Disease progression, the incidence and severity of arthritis, were determined. Serum concentration of CII-specific IgG was measured by enzyme-linked immunosorbent assay. Systemic administration of EPS markedly reduced CII-specific antibody production. Moreover, EPS significantly ameliorated arthritis in the active models of CIA, especially, when LPS alone was used as an adjuvant. In contrast, when arthritogenic antibodies were injected to mice in high amounts, the effect of EPS on the development of passive CIA was negligible and transient. These results show that EPS can suppress active CIA by the inhibition of arthritogenic antibodies production. Therefore, we suggest that EPS or EPS-producing probiotics may be promising agents for the supporting therapy of patients with rheumatoid arthritis.

show abstract

“…The strictly humoral collagen antibody-induced arthritis (CAIA) mouse model shows that anti-CII can initiate arthritis [5,6]. CAIA has been induced in mice lacking an adaptive immune system, showing a direct role of anti-CII in arthritis development [7].…”

Section: Introductionmentioning

confidence: 99%

Anti-type II collagen immune complex-induced granulocyte reactivity is associated with joint erosions in RA patients with anti-collagen antibodies

Manivel¹,

Sohrabian²,

Wick³

et al. 2015

Arthritis Res Ther

View full text Add to dashboard Cite

IntroductionRheumatoid arthritis (RA) patients with autoantibodies against collagen type II (CII) are characterized by acute RA onset with elevated inflammatory measures and early joint erosions as well as increased production of tumor necrosis factor-α (ΤΝF-α) by peripheral blood mononuclear cells (PBMC) stimulated by anti-CII immune complexes (IC) in vitro. Polymorphonuclear granulocytes (PMN) are abundant in RA synovial fluids, where they might interact directly with anti-CII IC in the articular cartilage, but no studies have investigated PMN responses towards anti-CII IC. The aim was to investigate whether PMN react towards anti-CII IC, and to what extent such reactivity might relate to the clinical acute onset RA phenotype associated with elevated levels of anti-CII.MethodsPMN and PBMC isolated from healthy donors were stimulated with IC made with a set of 72 baseline patient sera (24 anti-CII positive, 48 anti-CII negative) chosen from a clinically well-characterized RA cohort with two-year radiological follow-up with Larsen scoring. PMN expression of cluster of differentiation (CD)11b, CD66b, CD16 and CD32 was measured by flow cytometry, whereas PMN production of myeloperoxidase (MPO) and interleukin (IL)-17, and PBMC production of ΤΝF-α was measured with enzyme linked immunosorbent assay.ResultsPMN expression of CD11b, CD66b and MPO, and PBMC production of ΤΝF-α were upregulated whereas PMN expression of CD16 and CD32 were downregulated by anti-CII IC. CD16, CD66b, and MPO production correlated to serum anti-CII levels (Spearman’s ρ = 0.315, 0.675 and 0.253, respectively). CD16 was associated with early joint erosions (P = 0.024, 0.034, 0.046 at baseline, one and two years) and CD66b was associated with changes in joint erosions (P = 0.017 and 0.016, at one and two years compared to baseline, respectively). CD66b was associated with baseline C-reactive protein and PBMC production of ΤΝF-α was associated with baseline erythrocyte sedimentation rate, in accordance with our earlier findings. No clinical associations were observed for MPO or IL-17.ConclusionPMN responses against anti-CII IC are more closely associated with early joint erosions than are PBMC cytokine responses. PMN reactivity against anti-CII IC may contribute to joint destruction in newly diagnosed RA patients with high levels of anti-CII.

show abstract

Collagen Type II-Specific Monoclonal Antibody-Induced Arthritis in Mice

Cited by 259 publications

References 61 publications

Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene

Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene

Lactobacillus rhamnosus Exopolysaccharide Ameliorates Arthritis Induced by the Systemic Injection of Collagen and Lipopolysaccharide in DBA/1 Mice

Anti-type II collagen immune complex-induced granulocyte reactivity is associated with joint erosions in RA patients with anti-collagen antibodies

Contact Info

Product

Resources

About