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- Kap, Yolanda S, et al.
(författare)
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Immune modulation by a tolerogenic MOG10-60 containing fusion protein in the marmoset experimental autoimmune encephalomyelitis model.
- 2015
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Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 1365-2249 .- 0009-9104. ; 180:1, s. 28-39
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Tidskriftsartikel (refereegranskat)abstract
- Current therapies for multiple sclerosis (MS), a chronic autoimmune neuroinflammatory disease, mostly target general cell populations or immune molecules, which may lead to a compromised immune system. A more directed strategy would be to re-enforce tolerance of the autoaggressive T cells that drive tissue inflammation and injury. In this study, we have investigated whether the course of experimental autoimmune encephalomyelitis (EAE) in mice and marmosets can be altered by a potent tolerizing fusion protein. In addition, a multiparameter immunological analysis was performed in marmosets to assess whether the treatment induces modulation of EAE-associated cellular and humoral immune reactions. The fusion protein, CTA1R9K-hMOG10-60-DD, contains a mutated cholera toxin A1 subunit (CTA1R9K), a dimer of the Ig binding D region of Staphylococcus aureus protein A (DD), and the human myelin oligodendrocyte glycoprotein (hMOG) sequence 10 to 60. We observed that intranasal application of CTA1R9K-hMOG10-60-DD seems to skew the immune response against MOG towards a regulatory function. We show a reduced number of circulating macrophages, reduced MOG-induced expansion of mononuclear cells in peripheral blood, reduced MOG-induced production of IL-17A in spleen, increased MOG-induced production of IL-4 and IL-10, and an increased percentage of cells expressing programmed cell death-1 (PD-1) and CC chemokine receptor 4 (CCR4). Nevertheless, the treatment did not detectably change the EAE course and pathology. Thus, despite a detectable effect on relevant immune parameters, the fusion protein failed to influence the clinical and pathological outcome of disease. This result warrants further development and improvement of this specifically targeted tolerance inducing therapy.
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| 2. |
- Lindh, Ingrid, et al.
(författare)
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Type II collagen antibody response is enriched in the synovial fluid of rheumatoid joints and directed to the same major epitopes as in collagen induced arthritis in primates and mice
- 2014
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Ingår i: Arthritis Research & Therapy. - London : BioMed Central (BMC). - 1478-6362 .- 1478-6354. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Antibodies towards type II collagen (CII) are detected in patients with rheumatoid arthritis (RA) and in non-human primates and rodents with collagen induced arthritis (CIA). We have previously shown that antibodies specific for several CII-epitopes are pathogenic using monoclonal antibodies from arthritic mice, although the role of different anti-CII epitopes has not been investigated in detail in other species. We therefore performed an inter-species comparative study of the autoantibody response to CII in patients with RA versus monkeys and mice with CIA. METHODS: Analysis of the full epitope repertoire along the disease course of CIA was performed using a library of CII triple-helical peptides. The antibody responses to the major CII epitopes were analyzed in sera and synovial fluid from RA patients, and in sera from rhesus monkeys (Macaca mulatta), common marmosets (Callithrix jacchus) and mice. RESULTS: Many CII epitopes including the major C1, U1, and J1 were associated with established CIA and arginine residues played an important role in the anti-CII antibody interactions. The major epitopes were also recognized in RA patients, both in sera and even more pronounced in synovial fluid: 77% of the patients had antibodies to the U1 epitope. The anti-CII immune response was not restricted to the anti-citrulline protein antibodies (ACPA) positive RA group. CONCLUSION: CII conformational dependent antibody responses are common in RA and are likely to originate from rheumatoid joints but did not show a correlation with ACPA response. Importantly, the fine specificity of the anti-CII response is similar with CIA in monkeys and rodents where the recognized epitopes are conserved and have a major pathogenic role. Thus, anti-CII antibodies may both contribute to, as well as be the consequence of, local joint inflammation. © 2014 Lindh et al.; licensee BioMed Central Ltd.
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