Inflammatory protein response in CDKL5-Rett syndrome: evidence of a subclinical smouldering inflammation

• Published in: Inflammation research 2017-03, Vol.66 (3), p.269-280
• Main Authors: Cortelazzo, Alessio, de Felice, Claudio, Leoncini, Silvia, Signorini, Cinzia, Guerranti, Roberto, Leoncini, Roberto, Armini, Alessandro, Bini, Luca, Ciccoli, Lucia, Hayek, Joussef
• Format: Article
• Language: English
• Subjects: Acute-Phase Reaction - genetics; Acute-Phase Reaction - immunology; Acute-Phase Reaction - metabolism; Adolescent; Allergology; Biomedical and Life Sciences; Biomedicine; Blood Proteins - immunology; Blood Proteins - metabolism; Child; Child, Preschool; Cytokines - blood; Cytokines - immunology; Dermatology; Dietary Supplements; Epileptic Syndromes; Fatty Acids, Omega-3 - pharmacology; Female; Humans; Immunology; Infant; Methyl-CpG-Binding Protein 2 - genetics; Neurology; Original Research Paper; Pharmacology/Toxicology; Protein-Serine-Threonine Kinases - genetics; Rett Syndrome - genetics; Rett Syndrome - immunology; Rett Syndrome - metabolism; Rheumatology; Spasms, Infantile - genetics; Spasms, Infantile - immunology; Spasms, Infantile - metabolism
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-016-1014-2

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.