PMID- 27900411
OWN - NLM
STAT- MEDLINE
DCOM- 20170526
LR  - 20211204
IS  - 1420-908X (Electronic)
IS  - 1023-3830 (Linking)
VI  - 66
IP  - 3
DP  - 2017 Mar
TI  - Inflammatory protein response in CDKL5-Rett syndrome: evidence of a subclinical 
      smouldering inflammation.
PG  - 269-280
LID - 10.1007/s00011-016-1014-2 [doi]
AB  - 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 (omega-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.
FAU - Cortelazzo, Alessio
AU  - Cortelazzo A
AD  - Child Neuropsychiatry Unit, University Hospital Azienda Ospedaliera Universitaria 
      Senese (AOUS), Viale M. Bracci 16, 53100, Siena, Italy. 
      alessio.cortelazzo@biologo.onb.it.
AD  - Department of Medical Biotechnologies, University of Siena, Via A. Moro 2, 53100, 
      Siena, Italy. alessio.cortelazzo@biologo.onb.it.
AD  - Clinical Pathology Laboratory Unit, University Hospital AOUS, Viale M. Bracci 16, 
      53100, Siena, Italy. alessio.cortelazzo@biologo.onb.it.
FAU - de Felice, Claudio
AU  - de Felice C
AD  - Neonatal Intensive Care Unit, University Hospital AOUS, Viale M. Bracci 16, 
      53100, Siena, Italy.
FAU - Leoncini, Silvia
AU  - Leoncini S
AD  - Child Neuropsychiatry Unit, University Hospital Azienda Ospedaliera Universitaria 
      Senese (AOUS), Viale M. Bracci 16, 53100, Siena, Italy.
AD  - Department of Molecular and Developmental Medicine, University of Siena, Via A. 
      Moro 6, 53100, Siena, Italy.
FAU - Signorini, Cinzia
AU  - Signorini C
AD  - Department of Molecular and Developmental Medicine, University of Siena, Via A. 
      Moro 6, 53100, Siena, Italy.
FAU - Guerranti, Roberto
AU  - Guerranti R
AD  - Department of Medical Biotechnologies, University of Siena, Via A. Moro 2, 53100, 
      Siena, Italy.
AD  - Clinical Pathology Laboratory Unit, University Hospital AOUS, Viale M. Bracci 16, 
      53100, Siena, Italy.
FAU - Leoncini, Roberto
AU  - Leoncini R
AD  - Department of Medical Biotechnologies, University of Siena, Via A. Moro 2, 53100, 
      Siena, Italy.
AD  - Clinical Pathology Laboratory Unit, University Hospital AOUS, Viale M. Bracci 16, 
      53100, Siena, Italy.
FAU - Armini, Alessandro
AU  - Armini A
AD  - Department of Life Sciences, University of Siena, Via A. Moro 2, 53100, Siena, 
      Italy.
FAU - Bini, Luca
AU  - Bini L
AD  - Department of Life Sciences, University of Siena, Via A. Moro 2, 53100, Siena, 
      Italy.
FAU - Ciccoli, Lucia
AU  - Ciccoli L
AD  - Department of Molecular and Developmental Medicine, University of Siena, Via A. 
      Moro 6, 53100, Siena, Italy.
FAU - Hayek, Joussef
AU  - Hayek J
AD  - Child Neuropsychiatry Unit, University Hospital Azienda Ospedaliera Universitaria 
      Senese (AOUS), Viale M. Bracci 16, 53100, Siena, Italy.
LA  - eng
PT  - Journal Article
DEP - 20161129
PL  - Switzerland
TA  - Inflamm Res
JT  - Inflammation research : official journal of the European Histamine Research 
      Society ... [et al.]
JID - 9508160
RN  - 0 (Blood Proteins)
RN  - 0 (Cytokines)
RN  - 0 (Fatty Acids, Omega-3)
RN  - 0 (MECP2 protein, human)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.22 (CDKL5 protein, human)
RN  - CDKL5 deficiency disorder
SB  - IM
MH  - Acute-Phase Reaction/genetics/*immunology/metabolism
MH  - Adolescent
MH  - Blood Proteins/immunology/metabolism
MH  - Child
MH  - Child, Preschool
MH  - Cytokines/blood/*immunology
MH  - Dietary Supplements
MH  - Epileptic Syndromes
MH  - Fatty Acids, Omega-3/pharmacology
MH  - Female
MH  - Humans
MH  - Infant
MH  - Methyl-CpG-Binding Protein 2/genetics
MH  - Protein Serine-Threonine Kinases/genetics
MH  - Rett Syndrome/genetics/*immunology/metabolism
MH  - Spasms, Infantile/genetics/*immunology/metabolism
OTO - NOTNLM
OT  - Acute-phase proteins
OT  - Cyclin-dependent kinase-like 5
OT  - Cytokines
OT  - Polyunsaturated fatty acids
OT  - Rett syndrome
OT  - Subclinical inflammation
EDAT- 2016/12/03 06:00
MHDA- 2017/05/27 06:00
CRDT- 2016/12/01 06:00
PHST- 2016/07/27 00:00 [received]
PHST- 2016/11/23 00:00 [accepted]
PHST- 2016/11/06 00:00 [revised]
PHST- 2016/12/03 06:00 [pubmed]
PHST- 2017/05/27 06:00 [medline]
PHST- 2016/12/01 06:00 [entrez]
AID - 10.1007/s00011-016-1014-2 [pii]
AID - 10.1007/s00011-016-1014-2 [doi]
PST - ppublish
SO  - Inflamm Res. 2017 Mar;66(3):269-280. doi: 10.1007/s00011-016-1014-2. Epub 2016 
      Nov 29.