Alessio Cortelazzo1,2,3, Claudio de Felice4, Silvia Leoncini5,6, Cinzia Signorini6, Roberto Guerranti7,8, Roberto Leoncini7,8, Alessandro Armini9, Luca Bini9, Lucia Ciccoli6, Joussef Hayek5. 1. Child Neuropsychiatry Unit, University Hospital Azienda Ospedaliera Universitaria Senese (AOUS), Viale M. Bracci 16, 53100, Siena, Italy. alessio.cortelazzo@biologo.onb.it. 2. Department of Medical Biotechnologies, University of Siena, Via A. Moro 2, 53100, Siena, Italy. alessio.cortelazzo@biologo.onb.it. 3. Clinical Pathology Laboratory Unit, University Hospital AOUS, Viale M. Bracci 16, 53100, Siena, Italy. alessio.cortelazzo@biologo.onb.it. 4. Neonatal Intensive Care Unit, University Hospital AOUS, Viale M. Bracci 16, 53100, Siena, Italy. 5. Child Neuropsychiatry Unit, University Hospital Azienda Ospedaliera Universitaria Senese (AOUS), Viale M. Bracci 16, 53100, Siena, Italy. 6. Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 6, 53100, Siena, Italy. 7. Department of Medical Biotechnologies, University of Siena, Via A. Moro 2, 53100, Siena, Italy. 8. Clinical Pathology Laboratory Unit, University Hospital AOUS, Viale M. Bracci 16, 53100, Siena, Italy. 9. Department of Life Sciences, University of Siena, Via A. Moro 2, 53100, Siena, Italy.
Abstract
BACKGROUND: Mutations in the cyclin-dependent kinase-like 5 gene cause a clinical variant of Rett syndrome (CDKL5-RTT). A role for the acute-phase response (APR) is emerging in typical RTT caused by methyl-CpG-binding protein 2 gene mutations (MECP2-RTT). No information is, to date, available on the inflammatory protein response in CDKL5-RTT. We evaluated, for the first time, the APR protein response in CDKL5-RTT. METHODS: Protein patterns in albumin- and IgG-depleted plasma proteome from CDKL5-RTT patients were evaluated by two-dimensional gel electrophoresis/mass spectrometry. The resulting data were related to circulating cytokines and compared to healthy controls or MECP2-RTT patients. The effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) were evaluated. RESULTS: CDKL5-RTT mutations resulted in a subclinical attenuated inflammation, specifically characterized by an overexpression of the complement component C3 and CD5 antigen-like, both strictly related to the inflammatory response. Cytokine dysregulation featuring a bulk increase of anti-inflammatory cytokines, predominantly IL-10, could explain the unchanged erythrocyte sedimentation rate and atypical features of inflammation in CDKL5-RTT. Omega-3 PUFAs were able to counterbalance the pro-inflammatory status. CONCLUSION: For the first time, we revealed a subclinical smouldering inflammation pattern in CDKL5-RTT consisting in the coexistence of an atypical APR coupled with a dysregulated cytokine response.
BACKGROUND: Mutations in the cyclin-dependent kinase-like 5 gene cause a clinical variant of Rett syndrome (CDKL5-RTT). A role for the acute-phase response (APR) is emerging in typical RTT caused by methyl-CpG-binding protein 2 gene mutations (MECP2-RTT). No information is, to date, available on the inflammatory protein response in CDKL5-RTT. We evaluated, for the first time, the APR protein response in CDKL5-RTT. METHODS: Protein patterns in albumin- and IgG-depleted plasma proteome from CDKL5-RTT patients were evaluated by two-dimensional gel electrophoresis/mass spectrometry. The resulting data were related to circulating cytokines and compared to healthy controls or MECP2-RTT patients. The effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) were evaluated. RESULTS:CDKL5-RTT mutations resulted in a subclinical attenuated inflammation, specifically characterized by an overexpression of the complement component C3 and CD5 antigen-like, both strictly related to the inflammatory response. Cytokine dysregulation featuring a bulk increase of anti-inflammatory cytokines, predominantly IL-10, could explain the unchanged erythrocyte sedimentation rate and atypical features of inflammation in CDKL5-RTT. Omega-3 PUFAs were able to counterbalance the pro-inflammatory status. CONCLUSION: For the first time, we revealed a subclinical smouldering inflammation pattern in CDKL5-RTT consisting in the coexistence of an atypical APR coupled with a dysregulated cytokine response.
Authors: Yonara G Cordeiro; Leandra M Mulder; René J M van Zeijl; Lindsay B Paskoski; Peter van Veelen; Arnoud de Ru; Ricardo F Strefezzi; Bram Heijs; Heidge Fukumasu Journal: Cancers (Basel) Date: 2021-11-24 Impact factor: 6.639