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Rheumatoid factor-p...
Rheumatoid factor-producing CD21low anergic clonal B-cells in essential mixed cryoglobulinaemia: a model for autoantigen-driven pathogenesis of infectious and non-infectious cryoglobulinaemias
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Del Padre, M. (författare)
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Minafò, Y. A. (författare)
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Marrapodi, R. (författare)
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Radicchio, G. (författare)
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Granata, M. (författare)
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- Camponeschi, Alessandro (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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Fiorilli, M. (författare)
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Quartuccio, L. (författare)
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De Vita, S. (författare)
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Casato, M. (författare)
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Colantuono, S. (författare)
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Visentini, M. (författare)
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(creator_code:org_t)
- 2020
- 2020
- Engelska.
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Ingår i: Clinical and experimental rheumatology. - 0392-856X. ; 38:2, s. 139-147
- Relaterad länk:
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https://gup.ub.gu.se...
Abstract
Ämnesord
Stäng
- OBJECTIVES: Essential mixed cryoglobulinaemia (EMC) is a disorder of B-cells producing rheumatoid factor (RF), and is clinically and immunologically similar to mixed cryoglobulinaemia (MC) related to hepatitis C virus (HCV-MC). We report here the first comprehensive analysis of B-cell clonality, phenotype and function in EMC. METHODS: The study population included 16 patients with EMC and 24 patients with HCV-MC. Molecular analysis was done for the detection of circulating clonal B cells and for B cell receptor sequencing. B-cell phenotype, proliferative response, apoptosis and ERK signaling were analysed by flow cytometry. RESULTS: Molecular analysis of immunoglobulin genes rearrangements revealed circulating B-cell clones in about half of patients, on average of smaller size than those found in HCV-MC patients. Sequence analysis showed usage of the same stereotyped RF-encoding B-cell receptors frequently expressed in HCV-MC and in primary Sjögren's syndrome. B-cells with low expression of CD21 (CD21low) and unusual homing and inhibitory receptors were increased in EMC and in HCV-MC, but at a significantly lower extent in the former. The CD21low B-cells of EMC and HCV-MC patients shared functional features of exhaustion and anergy, namely reduced proliferation upon ligation of Toll-like receptor 9, high constitutive expression of phosphorylated ERK, and proneness to spontaneous apoptosis. CONCLUSIONS: Our findings suggest a common pathogenetic mechanism in EMC, HCV-MC and primary Sjögren's syndrome, consisting of autoantigen-driven clonal expansion and exhaustion of selected RF-producing B-cells. The more massive clonal expansion in HCV-MC may be due to co-stimulatory signals provided by the virus.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
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- Av författaren/redakt...
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Del Padre, M.
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Minafò, Y. A.
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Marrapodi, R.
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Radicchio, G.
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Granata, M.
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Camponeschi, Ale ...
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visa fler...
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Fiorilli, M.
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Quartuccio, L.
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De Vita, S.
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Casato, M.
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Colantuono, S.
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Visentini, M.
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visa färre...
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Göteborgs universitet