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Anti-Citrullinated ...
Anti-Citrullinated Protein Antibody Reactivity towards Neutrophil-Derived Antigens : Clonal Diversity and Inter-Individual Variation
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- Circiumaru, Alexandra (författare)
- Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden.;Stockholm Hlth Serv, Ctr Rheumatol, Acad Specialist Ctr, S-11365 Stockholm, Sweden.
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- Afonso, Marcelo Gomes (författare)
- Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden.
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- Wahamaa, Heidi (författare)
- Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden.
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- Krishnamurthy, Akilan (författare)
- Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden.
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- Hansson, Monika (författare)
- Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden.
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- Mathsson Alm, Linda (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Thermo Fisher Sci, S-75450 Uppsala, Sweden.
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- Keszei, Marton (författare)
- Karolinska Institutet
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- Stalesen, Ragnhild (författare)
- Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden.
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- Ottosson, Lars (författare)
- Karolinska Inst, Dept Womens & Childrens Hlth, Div Pediat Endocrinol, S-17176 Stockholm, Sweden.
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- de Vries, Charlotte (författare)
- Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden.
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- Shelef, Miriam A. (författare)
- Univ Wisconsin, Dept Med, Madison, WI 53705 USA.;William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA.
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- Malmstrom, Vivianne (författare)
- Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden.
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- Klareskog, Lars (författare)
- Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden.
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- Catrina, Anca I. (författare)
- Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden.;Stockholm Hlth Serv, Ctr Rheumatol, Acad Specialist Ctr, S-11365 Stockholm, Sweden.
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- Gronwall, Caroline (författare)
- Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden.
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- Hensvold, Aase (författare)
- Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden.;Stockholm Hlth Serv, Ctr Rheumatol, Acad Specialist Ctr, S-11365 Stockholm, Sweden.
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- Rethi, Bence (författare)
- Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden.
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Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden;Stockholm Hlth Serv, Ctr Rheumatol, Acad Specialist Ctr, S-11365 Stockholm, Sweden. Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden. (creator_code:org_t)
- 2023-03-31
- 2023
- Engelska.
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 13:4
- Relaterad länk:
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.3...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Background: Why the adaptive immune system turns against citrullinated antigens in rheumatoid arthritis (RA) and whether anti-citrullinated protein antibodies (ACPAs) contribute to pathogenesis are questions that have triggered intense research, but still are not fully answered. Neutrophils may be crucial in this context, both as sources of citrullinated antigens and also as targets of ACPAs. To better understand how ACPAs and neutrophils contribute to RA, we studied the reactivity of a broad spectrum of RA patient-derived ACPA clones to activated or resting neutrophils, and we also compared neutrophil binding using polyclonal ACPAs from different patients.Methods: Neutrophils were activated by Ca2+ ionophore, PMA, nigericin, zymosan or IL-8, and ACPA binding was studied using flow cytometry and confocal microscopy. The roles of PAD2 and PAD4 were studied using PAD-deficient mice or the PAD4 inhibitor BMS-P5.Results: ACPAs broadly targeted NET-like structures, but did not bind to intact cells or influence NETosis. We observed high clonal diversity in ACPA binding to neutrophil-derived antigens. PAD2 was dispensable, but most ACPA clones required PAD4 for neutrophil binding. Using ACPA preparations from different patients, we observed high patient-to-patient variability in targeting neutrophil-derived antigens and similarly in another cellular effect of ACPAs, the stimulation of osteoclast differentiation.Conclusions: Neutrophils can be important sources of citrullinated antigens under conditions that lead to PAD4 activation, NETosis and the extrusion of intracellular material. A substantial clonal diversity in targeting neutrophils and a high variability among individuals in neutrophil binding and osteoclast stimulation suggest that ACPAs may influence RA-related symptoms with high patient-to-patient variability.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Nyckelord
- rheumatoid arthritis
- ACPA
- neutrophil
- NETosis
- citrullination
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Circiumaru, Alex ...
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Afonso, Marcelo ...
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Wahamaa, Heidi
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Krishnamurthy, A ...
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Hansson, Monika
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Mathsson Alm, Li ...
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visa fler...
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Keszei, Marton
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Stalesen, Ragnhi ...
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Ottosson, Lars
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de Vries, Charlo ...
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Shelef, Miriam A ...
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Malmstrom, Vivia ...
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Klareskog, Lars
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Catrina, Anca I.
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Gronwall, Caroli ...
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Hensvold, Aase
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Rethi, Bence
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Reumatologi och ...
- Artiklar i publikationen
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Biomolecules
- Av lärosätet
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Uppsala universitet
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Karolinska Institutet