Impairments in Peripheral Blood T Effector and T Regulatory Lymphocytes in Bipolar Disorder Are Associated with Staging
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Impairments in Peripheral Blood T Effector and T Regulatory Lymphocytes in Bipolar Disorder Are Associated with Staging of Illness and Anti-cytomegalovirus IgG Levels Michael Maes 1,2,3
&
Joao Victor Nani 4 & Cristiano Noto 5 & Lucas Rizzo 6 & Mirian A.F. Hayashi 4,7 & Elisa Brietzke 8,9
Received: 10 March 2020 / Accepted: 1 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract There is now evidence that, based on cytokine profiles, bipolar disorder (BD) is accompanied by simultaneous activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS), and that both components may be associated with the staging of illness. Nevertheless, no BD studies have evaluated the IRS/CIRS ratio using CD (cluster of differentiation) molecules expressed by peripheral blood activated T effector (Teff) and T regulatory (Treg) subpopulations. This study examined Teff/Treg subsets both before and after ex vivo anti-CD3/CD28 stimulation using flow cytometric immunophenotyping in 25 symptomatic remitted BD patients and 21 healthy controls and assessed human cytomegalovirus (HCMV)–specific IgG antibodies. BD is associated with a significantly lowered frequency of unstimulated CD3 + CD8 + CD71+ and CD4 + CD25 + FOXP3 and increased CD4 + CD25 + FOXP3 + CD152+ frequencies and with lowered stimulated frequencies of CD3 + CD8 + CD71+, CD4 + CD25 + FOXP3 + CD152+, and CD4 + CD25 + FOXP3 + GARP cells and, consequently, by an increased stimulated Teff/Treg ratio. Moreover, the number of manic, but not hypomanic or depressive episodes, is significantly and negatively associated with the stimulated proportions of CD3 + CD4 + CD154+, and CD69+ and CD71+ expression on CD4+ and CD8+ cells, while duration of illness (≥ 10 years) is accompanied by a depleted frequency of stimulated CD152+ Treg, and CD154+ and CD71+ CD4+ T cells. BD and anti-human cytomegalovirus (HCMV) IgG levels significantly interact to decrease the expression of CD4 + CD25 + FOXP+GARP T phenotypes. In conclusion, in BD patients, immune injuries, staging, and HCMV seropositivity interact and cause CIRS dysfunctions and exaggerated IRS responses, which play a key role in parainflammation and neuroaffective toxicity. HCMV seropositivity contributes to an immune-risk phenotype in BD.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-02110-1) contains supplementary material, which is available to authorized users. * Michael Maes [email protected]; https://scholar.google.co.th/ citations?user=1wzMZ7UAAAAJ&hl=th&oi=ao
2
Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria
3
* Elisa Brietzke [email protected]
IMPACT Strategic Research Center, Deakin University, Geelong, Australia
4
Joao Victor Nani [email protected]
Post-Graduation Program of Psychiatry and Medical Psychology, Federal University of Sao Paulo, Sao Paulo, SP, Brazil
5
Cristiano Noto [email protected]
Early Psychosis Group (GAPi),
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