Type II collagen–specific antibodies induce cartilage damage in mice independent of inflammation

Croxford, Allyson Michelle; Whittingham, Senga; McNaughton, Donald; Nandakumar, Kutty Selva; Holmdahl, Rikard; Rowley, Merrill J.

doi:10.1002/art.37805

Cited by 22 publications

(26 citation statements)

References 48 publications

(68 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Investigations by Holmdahl and colleagues have shown that anti-CII can adhere to intact joint cartilage after intraperitoneal or intravenous injection [44,45], but these studies do not explain how such ICs will be in contact with responder cells in the synovial fluid. Studies from Jasin and colleagues indicate that binding of CII antibodies to an intact cartilage surface is dependent on neutrophil elastase-induced damage of the thin layer of small proteins covering the intact joint cartilage [46-48].…”

Section: Discussionmentioning

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

Section: Discussionmentioning

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

show abstract

“…This model replicates many aspects of the human effector phase of RA [21]. It occurs independently of any direct activity of B and T cells, allowing effector processes to be studied independently of the events that occur during disease induction [22]. The articular inflammation and cellular infiltration characteristics of the effector stage are attributable to deposited immune complexes and activation of complement and Fc receptors (FcR) [21,23].…”

Section: Discussionmentioning

confidence: 99%

“…The articular inflammation and cellular infiltration characteristics of the effector stage are attributable to deposited immune complexes and activation of complement and Fc receptors (FcR) [21,23]. Cartilage and bone erosion follows the activation of macrophages, lymphocytes, and synoviocytes and production of MMPs and cytokines [21,22]. …”

Section: Discussionmentioning

confidence: 99%

Exogenous IFN-beta regulates the RANKL-c-Fos-IFN-beta signaling pathway in the collagen antibody-induced arthritis model

et al. 2014

View full text Add to dashboard Cite

BackgroundAlthough a variety of drugs have been used to treat the symptoms of rheumatoid arthritis (RA), none of them are able to cure the disease. Interferon β (IFN-β) has pleiotropic effects on RA, but whether it can be used to treat RA remains globally controversial. Thus, in this study we tested the effects of IFN-β on RA patients and on collagen antibody-induced arthritis (CAIA) model mice.MethodsThe cytokine and auto-antibody expression profiles in the serum and synovial fluid (SF) from RA patients were assessed using enzyme-linked immunosorbent assay (ELISA) and compared with the results from osteoarthritis (OA) patients. Exogenous IFN-β was administered to RA patients and CAIA model mice, and the therapeutic effects were evaluated. Endogenous IFN-β expression in the joint bones of CAIA model mice was evaluated by quantitative real-time PCR (qRT-PCR). The effects of exogenous IFN-β on CAIA model mice were assessed using a clinical scoring system, hematoxylin eosin and safranin-O with fast green counterstain histology, molybdenum target X-ray, and tartrate-resistant acid phosphatase (TRAP) staining. The RANKL-RANK signaling pathway was analyzed using qRT-PCR. The RAW 264.7 cell line was differentiated into osteoclasts with RANKL stimulation and then treated with exogenous IFN-β.ResultsThe expression of inflammatory cytokines (IFN-γ, IL-17, MMP-3, and RANKL) and auto-antibodies (CII antibodies, RF-IgM, and anti-CCP/GPI) were significantly higher in RA compared with OA patients. After IFN-β intervention, some clinical symptoms in RA patients were partially alleviated, and the expression of IFN-γ, IL-17, MMP-3, and OPG) returned to normal levels. In the CAIA model, the expression of endogenous IFN-β in the joint bones was decreased. After IFN-β administration, the arthritis scores were decreased; synovial inflammation, cartilage, and bone destruction were clearly attenuated; and the expression of c-Fos and NFATc1 were reduced, while RANKL and TRAF6 expression was unchanged. In addition, exogenous IFN-β directly inhibited RANKL-induced osteoclastogenesis.ConclusionsExogenous IFN-β administration immunomodulates CAIA, may reduce joint inflammation and, perhaps more importantly, bone destruction by inhibiting the RANKL-c-Fos signaling pathway. Exogenous IFN-β intervention should be selectively used on RA patients because it may only be useful for RA patients with low endogenous IFN-β expression.

show abstract

“…Injection of aCII antibodies is known to trigger a series of pathogenic events, including induction of pain (arthralgia), destabilization of cartilage, infiltration of joints by lymphocytes and proliferation of macrophages [5,[15][16][17]. If labelled mannan is injected together with unlabelled mannan, used at doses that will later trigger inflammation in skin and in joints, the transport of mannan to various tissues will be more efficient.…”

Section: Discussionmentioning

confidence: 99%

Rapid spread of mannan to the immune system, skin and joints within 6 hours after local exposure

Hagert

Siitonen

et al. 2019

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Psoriasis (Ps), psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are common diseases dependent on environmental factors that activate the immune system in unknown ways. Mannan is a group of polysaccharides common in the environment; they are potentially pathogenic, because at least some of them induce Ps-, PsA-and RA-like inflammation in mice. Here, we used positron emission tomography/computed tomography to examine in-vivo transport and spread of mannan labelled with fluorine-18 [ 18 F]. The results showed that mannan was transported to joints (knee) and bone marrow (tibia) of mice within 6 h after intraperitoneal injection. The time it took to transport mannan, and its presence in blood, indicated cellular transport of mannan within the circulatory system. In addition, mannan was filtered mainly through the spleen and liver. [ 18 F]fluoromannan was excreted via kidneys, small intestine and, to some extent, the mouth. In conclusion, mannan reaches joints rapidly after injection, which may explain why mannan-induced inflammatory disease is targeted to these tissues.

show abstract

Type II collagen–specific antibodies induce cartilage damage in mice independent of inflammation

Cited by 22 publications

References 48 publications

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

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

Exogenous IFN-beta regulates the RANKL-c-Fos-IFN-beta signaling pathway in the collagen antibody-induced arthritis model

Rapid spread of mannan to the immune system, skin and joints within 6 hours after local exposure

Contact Info

Product

Resources

About