IL-6 Autoantibodies Predict Lower Platelet Counts and Altered Plasma Cytokine Profiles in Healthy Blood Donors: Results From the Danish Blood Donor Study

Cytokine-specific autoantibodies (c-aAb) represent a novel type of immune dysfunction. Though they have been detected in both patient cohorts and healthy individuals, and have immunomodulatory properties, the full extent of their influence remains unknown. Based on the critical role of several cytok...
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Autor*in:	Jakob Hjorth von Stemann [verfasserIn] Ole Birger Vesterager Pedersen [verfasserIn] Henrik Hjalgrim [verfasserIn] Christian Erikstrup [verfasserIn] Henrik Ullum [verfasserIn] Joseph Dowsett [verfasserIn] Lise Wegner Thørner [verfasserIn] Margit Anita Hørup Larsen [verfasserIn] Erik Sørensen [verfasserIn] Morten Bagge Hansen [verfasserIn] Sisse Rye Ostrowski [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	autoimmunity IL-6 platelets epidemiology blood donors cytokine autoantibodies

Übergeordnetes Werk:	In: Frontiers in Medicine - Frontiers Media S.A., 2014, 9(2022)
Übergeordnetes Werk:	volume:9 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fmed.2022.914262

Katalog-ID:	DOAJ021250693

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520			\|a Cytokine-specific autoantibodies (c-aAb) represent a novel type of immune dysfunction. Though they have been detected in both patient cohorts and healthy individuals, and have immunomodulatory properties, the full extent of their influence remains unknown. Based on the critical role of several cytokines in thrombopoiesis, we investigated if there is an association between c-aAb and platelet variables in healthy individuals, with a specific focus on c-aAb against a known thrombopoietic cytokine, IL-6. Using platelet count and mean platelet volume in 3,569 healthy participants of the Danish Blood Donor Study as dependent variables, we performed a series of multivariate regression analyses using five cytokine autoantibodies, including IL-6 c-aAb, as independent variables. In men, high titers of IL-6 c-aAb were negatively associated with platelet counts (β = −24 *109/l (95% confidence interval −43 to −6), p = 0.008) and positively associated with mean platelet volume (β = 0.4 fL (95% confidence interval 0.0–0.7) p = 0.043). These associations were exacerbated when adjusting for undetectable C-reactive protein levels, which we used as a proxy for c-aAb mediated IL-6 inhibition in vivo. Furthermore, in a smaller subgroup, individuals with high vs. low titer IL-6 c-aAb had different profiles of plasma IL-6, IL-10, TNFα and TPO, further suggesting a functional inhibition of IL-6 by high titers of circulating IL-6 c-aAb. We therefore speculate that in addition to their immunomodulatory potential IL-6 c-aAb may interfere with thrombopoiesis – directly or indirectly – under normal physiological conditions. This study is the first to suggest an influence of c-aAb on platelets in healthy individuals, beyond their apparent effects on immune competence.
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allfields	10.3389/fmed.2022.914262 doi (DE-627)DOAJ021250693 (DE-599)DOAJdf33930ae0e94dca9c54fc82e5f7c96c DE-627 ger DE-627 rakwb eng R5-920 Jakob Hjorth von Stemann verfasserin aut IL-6 Autoantibodies Predict Lower Platelet Counts and Altered Plasma Cytokine Profiles in Healthy Blood Donors: Results From the Danish Blood Donor Study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cytokine-specific autoantibodies (c-aAb) represent a novel type of immune dysfunction. Though they have been detected in both patient cohorts and healthy individuals, and have immunomodulatory properties, the full extent of their influence remains unknown. Based on the critical role of several cytokines in thrombopoiesis, we investigated if there is an association between c-aAb and platelet variables in healthy individuals, with a specific focus on c-aAb against a known thrombopoietic cytokine, IL-6. Using platelet count and mean platelet volume in 3,569 healthy participants of the Danish Blood Donor Study as dependent variables, we performed a series of multivariate regression analyses using five cytokine autoantibodies, including IL-6 c-aAb, as independent variables. In men, high titers of IL-6 c-aAb were negatively associated with platelet counts (β = −24 *109/l (95% confidence interval −43 to −6), p = 0.008) and positively associated with mean platelet volume (β = 0.4 fL (95% confidence interval 0.0–0.7) p = 0.043). These associations were exacerbated when adjusting for undetectable C-reactive protein levels, which we used as a proxy for c-aAb mediated IL-6 inhibition in vivo. Furthermore, in a smaller subgroup, individuals with high vs. low titer IL-6 c-aAb had different profiles of plasma IL-6, IL-10, TNFα and TPO, further suggesting a functional inhibition of IL-6 by high titers of circulating IL-6 c-aAb. We therefore speculate that in addition to their immunomodulatory potential IL-6 c-aAb may interfere with thrombopoiesis – directly or indirectly – under normal physiological conditions. This study is the first to suggest an influence of c-aAb on platelets in healthy individuals, beyond their apparent effects on immune competence. autoimmunity IL-6 platelets epidemiology blood donors cytokine autoantibodies Medicine (General) Ole Birger Vesterager Pedersen verfasserin aut Ole Birger Vesterager Pedersen verfasserin aut Henrik Hjalgrim verfasserin aut Henrik Hjalgrim verfasserin aut Henrik Hjalgrim verfasserin aut Henrik Hjalgrim verfasserin aut Christian Erikstrup verfasserin aut Henrik Ullum verfasserin aut Joseph Dowsett verfasserin aut Lise Wegner Thørner verfasserin aut Margit Anita Hørup Larsen verfasserin aut Erik Sørensen verfasserin aut Morten Bagge Hansen verfasserin aut Morten Bagge Hansen verfasserin aut Sisse Rye Ostrowski verfasserin aut Sisse Rye Ostrowski verfasserin aut In Frontiers in Medicine Frontiers Media S.A., 2014 9(2022) (DE-627)789482991 (DE-600)2775999-4 2296858X nnns volume:9 year:2022 https://doi.org/10.3389/fmed.2022.914262 kostenfrei https://doaj.org/article/df33930ae0e94dca9c54fc82e5f7c96c kostenfrei https://www.frontiersin.org/articles/10.3389/fmed.2022.914262/full kostenfrei https://doaj.org/toc/2296-858X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2022
spelling	10.3389/fmed.2022.914262 doi (DE-627)DOAJ021250693 (DE-599)DOAJdf33930ae0e94dca9c54fc82e5f7c96c DE-627 ger DE-627 rakwb eng R5-920 Jakob Hjorth von Stemann verfasserin aut IL-6 Autoantibodies Predict Lower Platelet Counts and Altered Plasma Cytokine Profiles in Healthy Blood Donors: Results From the Danish Blood Donor Study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cytokine-specific autoantibodies (c-aAb) represent a novel type of immune dysfunction. Though they have been detected in both patient cohorts and healthy individuals, and have immunomodulatory properties, the full extent of their influence remains unknown. Based on the critical role of several cytokines in thrombopoiesis, we investigated if there is an association between c-aAb and platelet variables in healthy individuals, with a specific focus on c-aAb against a known thrombopoietic cytokine, IL-6. Using platelet count and mean platelet volume in 3,569 healthy participants of the Danish Blood Donor Study as dependent variables, we performed a series of multivariate regression analyses using five cytokine autoantibodies, including IL-6 c-aAb, as independent variables. In men, high titers of IL-6 c-aAb were negatively associated with platelet counts (β = −24 *109/l (95% confidence interval −43 to −6), p = 0.008) and positively associated with mean platelet volume (β = 0.4 fL (95% confidence interval 0.0–0.7) p = 0.043). These associations were exacerbated when adjusting for undetectable C-reactive protein levels, which we used as a proxy for c-aAb mediated IL-6 inhibition in vivo. Furthermore, in a smaller subgroup, individuals with high vs. low titer IL-6 c-aAb had different profiles of plasma IL-6, IL-10, TNFα and TPO, further suggesting a functional inhibition of IL-6 by high titers of circulating IL-6 c-aAb. We therefore speculate that in addition to their immunomodulatory potential IL-6 c-aAb may interfere with thrombopoiesis – directly or indirectly – under normal physiological conditions. This study is the first to suggest an influence of c-aAb on platelets in healthy individuals, beyond their apparent effects on immune competence. autoimmunity IL-6 platelets epidemiology blood donors cytokine autoantibodies Medicine (General) Ole Birger Vesterager Pedersen verfasserin aut Ole Birger Vesterager Pedersen verfasserin aut Henrik Hjalgrim verfasserin aut Henrik Hjalgrim verfasserin aut Henrik Hjalgrim verfasserin aut Henrik Hjalgrim verfasserin aut Christian Erikstrup verfasserin aut Henrik Ullum verfasserin aut Joseph Dowsett verfasserin aut Lise Wegner Thørner verfasserin aut Margit Anita Hørup Larsen verfasserin aut Erik Sørensen verfasserin aut Morten Bagge Hansen verfasserin aut Morten Bagge Hansen verfasserin aut Sisse Rye Ostrowski verfasserin aut Sisse Rye Ostrowski verfasserin aut In Frontiers in Medicine Frontiers Media S.A., 2014 9(2022) (DE-627)789482991 (DE-600)2775999-4 2296858X nnns volume:9 year:2022 https://doi.org/10.3389/fmed.2022.914262 kostenfrei https://doaj.org/article/df33930ae0e94dca9c54fc82e5f7c96c kostenfrei https://www.frontiersin.org/articles/10.3389/fmed.2022.914262/full kostenfrei https://doaj.org/toc/2296-858X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2022
allfields_unstemmed	10.3389/fmed.2022.914262 doi (DE-627)DOAJ021250693 (DE-599)DOAJdf33930ae0e94dca9c54fc82e5f7c96c DE-627 ger DE-627 rakwb eng R5-920 Jakob Hjorth von Stemann verfasserin aut IL-6 Autoantibodies Predict Lower Platelet Counts and Altered Plasma Cytokine Profiles in Healthy Blood Donors: Results From the Danish Blood Donor Study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cytokine-specific autoantibodies (c-aAb) represent a novel type of immune dysfunction. Though they have been detected in both patient cohorts and healthy individuals, and have immunomodulatory properties, the full extent of their influence remains unknown. Based on the critical role of several cytokines in thrombopoiesis, we investigated if there is an association between c-aAb and platelet variables in healthy individuals, with a specific focus on c-aAb against a known thrombopoietic cytokine, IL-6. Using platelet count and mean platelet volume in 3,569 healthy participants of the Danish Blood Donor Study as dependent variables, we performed a series of multivariate regression analyses using five cytokine autoantibodies, including IL-6 c-aAb, as independent variables. In men, high titers of IL-6 c-aAb were negatively associated with platelet counts (β = −24 *109/l (95% confidence interval −43 to −6), p = 0.008) and positively associated with mean platelet volume (β = 0.4 fL (95% confidence interval 0.0–0.7) p = 0.043). These associations were exacerbated when adjusting for undetectable C-reactive protein levels, which we used as a proxy for c-aAb mediated IL-6 inhibition in vivo. Furthermore, in a smaller subgroup, individuals with high vs. low titer IL-6 c-aAb had different profiles of plasma IL-6, IL-10, TNFα and TPO, further suggesting a functional inhibition of IL-6 by high titers of circulating IL-6 c-aAb. We therefore speculate that in addition to their immunomodulatory potential IL-6 c-aAb may interfere with thrombopoiesis – directly or indirectly – under normal physiological conditions. This study is the first to suggest an influence of c-aAb on platelets in healthy individuals, beyond their apparent effects on immune competence. autoimmunity IL-6 platelets epidemiology blood donors cytokine autoantibodies Medicine (General) Ole Birger Vesterager Pedersen verfasserin aut Ole Birger Vesterager Pedersen verfasserin aut Henrik Hjalgrim verfasserin aut Henrik Hjalgrim verfasserin aut Henrik Hjalgrim verfasserin aut Henrik Hjalgrim verfasserin aut Christian Erikstrup verfasserin aut Henrik Ullum verfasserin aut Joseph Dowsett verfasserin aut Lise Wegner Thørner verfasserin aut Margit Anita Hørup Larsen verfasserin aut Erik Sørensen verfasserin aut Morten Bagge Hansen verfasserin aut Morten Bagge Hansen verfasserin aut Sisse Rye Ostrowski verfasserin aut Sisse Rye Ostrowski verfasserin aut In Frontiers in Medicine Frontiers Media S.A., 2014 9(2022) (DE-627)789482991 (DE-600)2775999-4 2296858X nnns volume:9 year:2022 https://doi.org/10.3389/fmed.2022.914262 kostenfrei https://doaj.org/article/df33930ae0e94dca9c54fc82e5f7c96c kostenfrei https://www.frontiersin.org/articles/10.3389/fmed.2022.914262/full kostenfrei https://doaj.org/toc/2296-858X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2022
allfieldsGer	10.3389/fmed.2022.914262 doi (DE-627)DOAJ021250693 (DE-599)DOAJdf33930ae0e94dca9c54fc82e5f7c96c DE-627 ger DE-627 rakwb eng R5-920 Jakob Hjorth von Stemann verfasserin aut IL-6 Autoantibodies Predict Lower Platelet Counts and Altered Plasma Cytokine Profiles in Healthy Blood Donors: Results From the Danish Blood Donor Study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cytokine-specific autoantibodies (c-aAb) represent a novel type of immune dysfunction. Though they have been detected in both patient cohorts and healthy individuals, and have immunomodulatory properties, the full extent of their influence remains unknown. Based on the critical role of several cytokines in thrombopoiesis, we investigated if there is an association between c-aAb and platelet variables in healthy individuals, with a specific focus on c-aAb against a known thrombopoietic cytokine, IL-6. Using platelet count and mean platelet volume in 3,569 healthy participants of the Danish Blood Donor Study as dependent variables, we performed a series of multivariate regression analyses using five cytokine autoantibodies, including IL-6 c-aAb, as independent variables. In men, high titers of IL-6 c-aAb were negatively associated with platelet counts (β = −24 *109/l (95% confidence interval −43 to −6), p = 0.008) and positively associated with mean platelet volume (β = 0.4 fL (95% confidence interval 0.0–0.7) p = 0.043). These associations were exacerbated when adjusting for undetectable C-reactive protein levels, which we used as a proxy for c-aAb mediated IL-6 inhibition in vivo. Furthermore, in a smaller subgroup, individuals with high vs. low titer IL-6 c-aAb had different profiles of plasma IL-6, IL-10, TNFα and TPO, further suggesting a functional inhibition of IL-6 by high titers of circulating IL-6 c-aAb. We therefore speculate that in addition to their immunomodulatory potential IL-6 c-aAb may interfere with thrombopoiesis – directly or indirectly – under normal physiological conditions. This study is the first to suggest an influence of c-aAb on platelets in healthy individuals, beyond their apparent effects on immune competence. autoimmunity IL-6 platelets epidemiology blood donors cytokine autoantibodies Medicine (General) Ole Birger Vesterager Pedersen verfasserin aut Ole Birger Vesterager Pedersen verfasserin aut Henrik Hjalgrim verfasserin aut Henrik Hjalgrim verfasserin aut Henrik Hjalgrim verfasserin aut Henrik Hjalgrim verfasserin aut Christian Erikstrup verfasserin aut Henrik Ullum verfasserin aut Joseph Dowsett verfasserin aut Lise Wegner Thørner verfasserin aut Margit Anita Hørup Larsen verfasserin aut Erik Sørensen verfasserin aut Morten Bagge Hansen verfasserin aut Morten Bagge Hansen verfasserin aut Sisse Rye Ostrowski verfasserin aut Sisse Rye Ostrowski verfasserin aut In Frontiers in Medicine Frontiers Media S.A., 2014 9(2022) (DE-627)789482991 (DE-600)2775999-4 2296858X nnns volume:9 year:2022 https://doi.org/10.3389/fmed.2022.914262 kostenfrei https://doaj.org/article/df33930ae0e94dca9c54fc82e5f7c96c kostenfrei https://www.frontiersin.org/articles/10.3389/fmed.2022.914262/full kostenfrei https://doaj.org/toc/2296-858X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2022
allfieldsSound	10.3389/fmed.2022.914262 doi (DE-627)DOAJ021250693 (DE-599)DOAJdf33930ae0e94dca9c54fc82e5f7c96c DE-627 ger DE-627 rakwb eng R5-920 Jakob Hjorth von Stemann verfasserin aut IL-6 Autoantibodies Predict Lower Platelet Counts and Altered Plasma Cytokine Profiles in Healthy Blood Donors: Results From the Danish Blood Donor Study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cytokine-specific autoantibodies (c-aAb) represent a novel type of immune dysfunction. Though they have been detected in both patient cohorts and healthy individuals, and have immunomodulatory properties, the full extent of their influence remains unknown. Based on the critical role of several cytokines in thrombopoiesis, we investigated if there is an association between c-aAb and platelet variables in healthy individuals, with a specific focus on c-aAb against a known thrombopoietic cytokine, IL-6. Using platelet count and mean platelet volume in 3,569 healthy participants of the Danish Blood Donor Study as dependent variables, we performed a series of multivariate regression analyses using five cytokine autoantibodies, including IL-6 c-aAb, as independent variables. In men, high titers of IL-6 c-aAb were negatively associated with platelet counts (β = −24 *109/l (95% confidence interval −43 to −6), p = 0.008) and positively associated with mean platelet volume (β = 0.4 fL (95% confidence interval 0.0–0.7) p = 0.043). These associations were exacerbated when adjusting for undetectable C-reactive protein levels, which we used as a proxy for c-aAb mediated IL-6 inhibition in vivo. Furthermore, in a smaller subgroup, individuals with high vs. low titer IL-6 c-aAb had different profiles of plasma IL-6, IL-10, TNFα and TPO, further suggesting a functional inhibition of IL-6 by high titers of circulating IL-6 c-aAb. We therefore speculate that in addition to their immunomodulatory potential IL-6 c-aAb may interfere with thrombopoiesis – directly or indirectly – under normal physiological conditions. This study is the first to suggest an influence of c-aAb on platelets in healthy individuals, beyond their apparent effects on immune competence. autoimmunity IL-6 platelets epidemiology blood donors cytokine autoantibodies Medicine (General) Ole Birger Vesterager Pedersen verfasserin aut Ole Birger Vesterager Pedersen verfasserin aut Henrik Hjalgrim verfasserin aut Henrik Hjalgrim verfasserin aut Henrik Hjalgrim verfasserin aut Henrik Hjalgrim verfasserin aut Christian Erikstrup verfasserin aut Henrik Ullum verfasserin aut Joseph Dowsett verfasserin aut Lise Wegner Thørner verfasserin aut Margit Anita Hørup Larsen verfasserin aut Erik Sørensen verfasserin aut Morten Bagge Hansen verfasserin aut Morten Bagge Hansen verfasserin aut Sisse Rye Ostrowski verfasserin aut Sisse Rye Ostrowski verfasserin aut In Frontiers in Medicine Frontiers Media S.A., 2014 9(2022) (DE-627)789482991 (DE-600)2775999-4 2296858X nnns volume:9 year:2022 https://doi.org/10.3389/fmed.2022.914262 kostenfrei https://doaj.org/article/df33930ae0e94dca9c54fc82e5f7c96c kostenfrei https://www.frontiersin.org/articles/10.3389/fmed.2022.914262/full kostenfrei https://doaj.org/toc/2296-858X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2022
language	English
source	In Frontiers in Medicine 9(2022) volume:9 year:2022
sourceStr	In Frontiers in Medicine 9(2022) volume:9 year:2022
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	autoimmunity IL-6 platelets epidemiology blood donors cytokine autoantibodies Medicine (General)
isfreeaccess_bool	true
container_title	Frontiers in Medicine
authorswithroles_txt_mv	Jakob Hjorth von Stemann @@aut@@ Ole Birger Vesterager Pedersen @@aut@@ Henrik Hjalgrim @@aut@@ Christian Erikstrup @@aut@@ Henrik Ullum @@aut@@ Joseph Dowsett @@aut@@ Lise Wegner Thørner @@aut@@ Margit Anita Hørup Larsen @@aut@@ Erik Sørensen @@aut@@ Morten Bagge Hansen @@aut@@ Sisse Rye Ostrowski @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	789482991
id	DOAJ021250693
language_de	englisch
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callnumber-first	R - Medicine
author	Jakob Hjorth von Stemann
spellingShingle	Jakob Hjorth von Stemann misc R5-920 misc autoimmunity misc IL-6 misc platelets misc epidemiology misc blood donors misc cytokine autoantibodies misc Medicine (General) IL-6 Autoantibodies Predict Lower Platelet Counts and Altered Plasma Cytokine Profiles in Healthy Blood Donors: Results From the Danish Blood Donor Study
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topic_title	R5-920 IL-6 Autoantibodies Predict Lower Platelet Counts and Altered Plasma Cytokine Profiles in Healthy Blood Donors: Results From the Danish Blood Donor Study autoimmunity IL-6 platelets epidemiology blood donors cytokine autoantibodies
topic	misc R5-920 misc autoimmunity misc IL-6 misc platelets misc epidemiology misc blood donors misc cytokine autoantibodies misc Medicine (General)
topic_unstemmed	misc R5-920 misc autoimmunity misc IL-6 misc platelets misc epidemiology misc blood donors misc cytokine autoantibodies misc Medicine (General)
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title	IL-6 Autoantibodies Predict Lower Platelet Counts and Altered Plasma Cytokine Profiles in Healthy Blood Donors: Results From the Danish Blood Donor Study
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title_full	IL-6 Autoantibodies Predict Lower Platelet Counts and Altered Plasma Cytokine Profiles in Healthy Blood Donors: Results From the Danish Blood Donor Study
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author_browse	Jakob Hjorth von Stemann Ole Birger Vesterager Pedersen Henrik Hjalgrim Christian Erikstrup Henrik Ullum Joseph Dowsett Lise Wegner Thørner Margit Anita Hørup Larsen Erik Sørensen Morten Bagge Hansen Sisse Rye Ostrowski
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title_sort	il-6 autoantibodies predict lower platelet counts and altered plasma cytokine profiles in healthy blood donors: results from the danish blood donor study
callnumber	R5-920
title_auth	IL-6 Autoantibodies Predict Lower Platelet Counts and Altered Plasma Cytokine Profiles in Healthy Blood Donors: Results From the Danish Blood Donor Study
abstract	Cytokine-specific autoantibodies (c-aAb) represent a novel type of immune dysfunction. Though they have been detected in both patient cohorts and healthy individuals, and have immunomodulatory properties, the full extent of their influence remains unknown. Based on the critical role of several cytokines in thrombopoiesis, we investigated if there is an association between c-aAb and platelet variables in healthy individuals, with a specific focus on c-aAb against a known thrombopoietic cytokine, IL-6. Using platelet count and mean platelet volume in 3,569 healthy participants of the Danish Blood Donor Study as dependent variables, we performed a series of multivariate regression analyses using five cytokine autoantibodies, including IL-6 c-aAb, as independent variables. In men, high titers of IL-6 c-aAb were negatively associated with platelet counts (β = −24 *109/l (95% confidence interval −43 to −6), p = 0.008) and positively associated with mean platelet volume (β = 0.4 fL (95% confidence interval 0.0–0.7) p = 0.043). These associations were exacerbated when adjusting for undetectable C-reactive protein levels, which we used as a proxy for c-aAb mediated IL-6 inhibition in vivo. Furthermore, in a smaller subgroup, individuals with high vs. low titer IL-6 c-aAb had different profiles of plasma IL-6, IL-10, TNFα and TPO, further suggesting a functional inhibition of IL-6 by high titers of circulating IL-6 c-aAb. We therefore speculate that in addition to their immunomodulatory potential IL-6 c-aAb may interfere with thrombopoiesis – directly or indirectly – under normal physiological conditions. This study is the first to suggest an influence of c-aAb on platelets in healthy individuals, beyond their apparent effects on immune competence.
abstractGer	Cytokine-specific autoantibodies (c-aAb) represent a novel type of immune dysfunction. Though they have been detected in both patient cohorts and healthy individuals, and have immunomodulatory properties, the full extent of their influence remains unknown. Based on the critical role of several cytokines in thrombopoiesis, we investigated if there is an association between c-aAb and platelet variables in healthy individuals, with a specific focus on c-aAb against a known thrombopoietic cytokine, IL-6. Using platelet count and mean platelet volume in 3,569 healthy participants of the Danish Blood Donor Study as dependent variables, we performed a series of multivariate regression analyses using five cytokine autoantibodies, including IL-6 c-aAb, as independent variables. In men, high titers of IL-6 c-aAb were negatively associated with platelet counts (β = −24 *109/l (95% confidence interval −43 to −6), p = 0.008) and positively associated with mean platelet volume (β = 0.4 fL (95% confidence interval 0.0–0.7) p = 0.043). These associations were exacerbated when adjusting for undetectable C-reactive protein levels, which we used as a proxy for c-aAb mediated IL-6 inhibition in vivo. Furthermore, in a smaller subgroup, individuals with high vs. low titer IL-6 c-aAb had different profiles of plasma IL-6, IL-10, TNFα and TPO, further suggesting a functional inhibition of IL-6 by high titers of circulating IL-6 c-aAb. We therefore speculate that in addition to their immunomodulatory potential IL-6 c-aAb may interfere with thrombopoiesis – directly or indirectly – under normal physiological conditions. This study is the first to suggest an influence of c-aAb on platelets in healthy individuals, beyond their apparent effects on immune competence.
abstract_unstemmed	Cytokine-specific autoantibodies (c-aAb) represent a novel type of immune dysfunction. Though they have been detected in both patient cohorts and healthy individuals, and have immunomodulatory properties, the full extent of their influence remains unknown. Based on the critical role of several cytokines in thrombopoiesis, we investigated if there is an association between c-aAb and platelet variables in healthy individuals, with a specific focus on c-aAb against a known thrombopoietic cytokine, IL-6. Using platelet count and mean platelet volume in 3,569 healthy participants of the Danish Blood Donor Study as dependent variables, we performed a series of multivariate regression analyses using five cytokine autoantibodies, including IL-6 c-aAb, as independent variables. In men, high titers of IL-6 c-aAb were negatively associated with platelet counts (β = −24 *109/l (95% confidence interval −43 to −6), p = 0.008) and positively associated with mean platelet volume (β = 0.4 fL (95% confidence interval 0.0–0.7) p = 0.043). These associations were exacerbated when adjusting for undetectable C-reactive protein levels, which we used as a proxy for c-aAb mediated IL-6 inhibition in vivo. Furthermore, in a smaller subgroup, individuals with high vs. low titer IL-6 c-aAb had different profiles of plasma IL-6, IL-10, TNFα and TPO, further suggesting a functional inhibition of IL-6 by high titers of circulating IL-6 c-aAb. We therefore speculate that in addition to their immunomodulatory potential IL-6 c-aAb may interfere with thrombopoiesis – directly or indirectly – under normal physiological conditions. This study is the first to suggest an influence of c-aAb on platelets in healthy individuals, beyond their apparent effects on immune competence.
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title_short	IL-6 Autoantibodies Predict Lower Platelet Counts and Altered Plasma Cytokine Profiles in Healthy Blood Donors: Results From the Danish Blood Donor Study
url	https://doi.org/10.3389/fmed.2022.914262 https://doaj.org/article/df33930ae0e94dca9c54fc82e5f7c96c https://www.frontiersin.org/articles/10.3389/fmed.2022.914262/full https://doaj.org/toc/2296-858X
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IL-6 Autoantibodies Predict Lower Platelet Counts and Altered Plasma Cytokine Profiles in Healthy Blood Donors: Results From the Danish Blood Donor Study

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