Autoantibodies reactive to adrenocorticotropic hormone can alter cortisol secretion in both aggressive and nonaggressive humans

Henning Værøy, C. Ádori, Romain Legrand, Nicolas Lucas, Jonathan Breton, Caroline Cottard, Jean Claude Do Rego, Céline Duparc, Estelle Louiset, Hervé Lefebvre, Pierre Déchelotte, Elin Western, Stein Andersson, Tomas Hökfelt, Sergueï O. Fetissov

Research output: Article

1 Citation (Scopus)

Abstract

Violent aggression in humans may involve a modified response to stress, but the underlying mechanisms are not well understood. Here we show that naturally present autoantibodies reactive to adrenocorticotropic hormone (ACTH) exhibit distinct epitope-binding profiles to ACTH peptide in subjects with a history of violent aggression compared with controls. Namely, while nonaggressive male controls displayed a preferential IgG binding to the ACTH central part (amino acids 11–24), subjects who had committed violent acts of aggression had IgG with increased affinity to ACTH, preferentially binding to its N terminus (amino acids 1–13). Purified IgGs from approximately half of the examined sera were able to block ACTH-induced cortisol secretion of human adrenal cells in vitro, irrespective of the source of sample (from a control subject or a violent aggressor). Nevertheless, in the resident–intruder test in mice, i.p. injection of residents with ACTH and IgG from aggressive subjects, but not from control subjects, shortened latency for the first attack against intruders. Immunohistochemical screening of violent aggressors’ sera on rat brain and pituitary sections did not show IgG binding to ACTH-producing cells, but 4 of 16 sera revealed selective binding to a nonidentified antigen in vasopressinergic neurons of the hypothalamic paraventricular and supraoptic nuclei. Thus, the data show that ACTH-reactive plasmatic IgGs exhibit differential epitope preference in control and violently aggressive subjects. These IgGs can modulate ACTH-induced cortisol secretion and, hence, are involved in the regulation of the stress response. However, the possible role of ACTH-reactive autoantibodies in aggressive behavior needs further investigation.

Original languageEnglish
Pages (from-to)E6576-E6584
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number28
DOIs
Publication statusPublished - júl. 10 2018

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Autoantibodies
Adrenocorticotropic Hormone
Hydrocortisone
Immunoglobulin G
Aggression
Epitopes
Serum
Amino Acids
Supraoptic Nucleus
Paraventricular Hypothalamic Nucleus
Neurons
Antigens
Peptides
Injections
Brain

ASJC Scopus subject areas

  • General

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Autoantibodies reactive to adrenocorticotropic hormone can alter cortisol secretion in both aggressive and nonaggressive humans. / Værøy, Henning; Ádori, C.; Legrand, Romain; Lucas, Nicolas; Breton, Jonathan; Cottard, Caroline; Do Rego, Jean Claude; Duparc, Céline; Louiset, Estelle; Lefebvre, Hervé; Déchelotte, Pierre; Western, Elin; Andersson, Stein; Hökfelt, Tomas; Fetissov, Sergueï O.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 28, 10.07.2018, p. E6576-E6584.

Research output: Article

Værøy, H, Ádori, C, Legrand, R, Lucas, N, Breton, J, Cottard, C, Do Rego, JC, Duparc, C, Louiset, E, Lefebvre, H, Déchelotte, P, Western, E, Andersson, S, Hökfelt, T & Fetissov, SO 2018, 'Autoantibodies reactive to adrenocorticotropic hormone can alter cortisol secretion in both aggressive and nonaggressive humans', Proceedings of the National Academy of Sciences of the United States of America, vol. 115, no. 28, pp. E6576-E6584. https://doi.org/10.1073/pnas.1720008115
Værøy, Henning ; Ádori, C. ; Legrand, Romain ; Lucas, Nicolas ; Breton, Jonathan ; Cottard, Caroline ; Do Rego, Jean Claude ; Duparc, Céline ; Louiset, Estelle ; Lefebvre, Hervé ; Déchelotte, Pierre ; Western, Elin ; Andersson, Stein ; Hökfelt, Tomas ; Fetissov, Sergueï O. / Autoantibodies reactive to adrenocorticotropic hormone can alter cortisol secretion in both aggressive and nonaggressive humans. In: Proceedings of the National Academy of Sciences of the United States of America. 2018 ; Vol. 115, No. 28. pp. E6576-E6584.
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abstract = "Violent aggression in humans may involve a modified response to stress, but the underlying mechanisms are not well understood. Here we show that naturally present autoantibodies reactive to adrenocorticotropic hormone (ACTH) exhibit distinct epitope-binding profiles to ACTH peptide in subjects with a history of violent aggression compared with controls. Namely, while nonaggressive male controls displayed a preferential IgG binding to the ACTH central part (amino acids 11–24), subjects who had committed violent acts of aggression had IgG with increased affinity to ACTH, preferentially binding to its N terminus (amino acids 1–13). Purified IgGs from approximately half of the examined sera were able to block ACTH-induced cortisol secretion of human adrenal cells in vitro, irrespective of the source of sample (from a control subject or a violent aggressor). Nevertheless, in the resident–intruder test in mice, i.p. injection of residents with ACTH and IgG from aggressive subjects, but not from control subjects, shortened latency for the first attack against intruders. Immunohistochemical screening of violent aggressors’ sera on rat brain and pituitary sections did not show IgG binding to ACTH-producing cells, but 4 of 16 sera revealed selective binding to a nonidentified antigen in vasopressinergic neurons of the hypothalamic paraventricular and supraoptic nuclei. Thus, the data show that ACTH-reactive plasmatic IgGs exhibit differential epitope preference in control and violently aggressive subjects. These IgGs can modulate ACTH-induced cortisol secretion and, hence, are involved in the regulation of the stress response. However, the possible role of ACTH-reactive autoantibodies in aggressive behavior needs further investigation.",
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AU - Værøy, Henning

AU - Ádori, C.

AU - Legrand, Romain

AU - Lucas, Nicolas

AU - Breton, Jonathan

AU - Cottard, Caroline

AU - Do Rego, Jean Claude

AU - Duparc, Céline

AU - Louiset, Estelle

AU - Lefebvre, Hervé

AU - Déchelotte, Pierre

AU - Western, Elin

AU - Andersson, Stein

AU - Hökfelt, Tomas

AU - Fetissov, Sergueï O.

PY - 2018/7/10

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N2 - Violent aggression in humans may involve a modified response to stress, but the underlying mechanisms are not well understood. Here we show that naturally present autoantibodies reactive to adrenocorticotropic hormone (ACTH) exhibit distinct epitope-binding profiles to ACTH peptide in subjects with a history of violent aggression compared with controls. Namely, while nonaggressive male controls displayed a preferential IgG binding to the ACTH central part (amino acids 11–24), subjects who had committed violent acts of aggression had IgG with increased affinity to ACTH, preferentially binding to its N terminus (amino acids 1–13). Purified IgGs from approximately half of the examined sera were able to block ACTH-induced cortisol secretion of human adrenal cells in vitro, irrespective of the source of sample (from a control subject or a violent aggressor). Nevertheless, in the resident–intruder test in mice, i.p. injection of residents with ACTH and IgG from aggressive subjects, but not from control subjects, shortened latency for the first attack against intruders. Immunohistochemical screening of violent aggressors’ sera on rat brain and pituitary sections did not show IgG binding to ACTH-producing cells, but 4 of 16 sera revealed selective binding to a nonidentified antigen in vasopressinergic neurons of the hypothalamic paraventricular and supraoptic nuclei. Thus, the data show that ACTH-reactive plasmatic IgGs exhibit differential epitope preference in control and violently aggressive subjects. These IgGs can modulate ACTH-induced cortisol secretion and, hence, are involved in the regulation of the stress response. However, the possible role of ACTH-reactive autoantibodies in aggressive behavior needs further investigation.

AB - Violent aggression in humans may involve a modified response to stress, but the underlying mechanisms are not well understood. Here we show that naturally present autoantibodies reactive to adrenocorticotropic hormone (ACTH) exhibit distinct epitope-binding profiles to ACTH peptide in subjects with a history of violent aggression compared with controls. Namely, while nonaggressive male controls displayed a preferential IgG binding to the ACTH central part (amino acids 11–24), subjects who had committed violent acts of aggression had IgG with increased affinity to ACTH, preferentially binding to its N terminus (amino acids 1–13). Purified IgGs from approximately half of the examined sera were able to block ACTH-induced cortisol secretion of human adrenal cells in vitro, irrespective of the source of sample (from a control subject or a violent aggressor). Nevertheless, in the resident–intruder test in mice, i.p. injection of residents with ACTH and IgG from aggressive subjects, but not from control subjects, shortened latency for the first attack against intruders. Immunohistochemical screening of violent aggressors’ sera on rat brain and pituitary sections did not show IgG binding to ACTH-producing cells, but 4 of 16 sera revealed selective binding to a nonidentified antigen in vasopressinergic neurons of the hypothalamic paraventricular and supraoptic nuclei. Thus, the data show that ACTH-reactive plasmatic IgGs exhibit differential epitope preference in control and violently aggressive subjects. These IgGs can modulate ACTH-induced cortisol secretion and, hence, are involved in the regulation of the stress response. However, the possible role of ACTH-reactive autoantibodies in aggressive behavior needs further investigation.

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KW - Neuroimmunology

KW - Psychoendocrinology

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