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Proc Natl Acad Sci U S A. 2018 Jul 10;115(28):E6576-E6584. doi: 10.1073/pnas.1720008115. Epub 2018 Jun 25.

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

Author information

Department of Psychiatric Research, Akershus University Hospital, N-1478 Nordbyhagen, Norway;
Department of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden.
Inserm UMR1073, Nutrition, Gut and Brain Laboratory, University of Rouen Normandy, 76000 Rouen, France.
Animal Behavior Platform, Service Commun d'Analyse Comportementale, University of Rouen Normandy, 76183 Rouen, France.
Inserm UMR1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, University of Rouen Normandy, 76821 Mont-Saint-Aignan, France.
Department of Endocrinology, Diabetes, and Metabolic Diseases, Rouen University Hospital, 76183 Rouen, France.
Nutrition Department, Rouen University Hospital, 76183 Rouen, France.
Department of Psychosomatic Medicine, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway.
Institute of Psychology, University of Oslo, 0315 Oslo, Norway.
Department of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden;
Inserm UMR1073, Nutrition, Gut and Brain Laboratory, University of Rouen Normandy, 76000 Rouen, France;


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.


HPA axis; autoantibodies; corticotropin; neuroimmunology; psychoendocrinology

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Conflict of interest statement: P.D. has received research grants from Nestlé and Fresenius Kabi and honoraria for speeches and consulting from Nestlé, Fresenius-Kabi, and Aguettant, is a cofounder of TargEDys SA, and is a member of its advisory board. S.O.F. is a cofounder of and serves as a consultant to TargEDys SA. N.L. and R.L. are currently employees of TargEDys SA. T.H. owns shares in AstraZeneca.

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