title: Peripheral whole blood FOXP3 TSDR methylation: a potential marker in severity assessment of autoimmune diseases and chronic infections.
abstract: Immune dysregulation is a cardinal feature of autoimmune diseases and chronic microbial infections. In particular, regulatory T cells are downregulated in autoimmune diseases while upregulated in chronic microbial infections. FOXP3 is the master regulator of Treg development. Treg-specific demethylated region (TSDR) is a highly conserved locus on the FOXP3 gene that is fully demethylated in natural Tregs but methylated in effector T cells. In our study, we used high resolution melt-polymerase chain reaction (HRM-PCR) to determine the FOXP3 TSDR methylation status in autoimmune diseases and chronic microbial infections. We found that FOXP3 TSDR to have the highest mean melting temperature (highly methylated) in active SLE patients compared to all the other groups (p < 0.001). The psoriasis group also had a significantly high mean melting temperature (78.62 ± 0.20) when compared with the inactive SLE group (78.49 ± 0.29, p < 0.05) and control group (78.44 ± 0.25, p < 0.01). There was no significant difference in melting temperature between inactive SLE and healthy controls. Disease activity in SLE was directly associated with methylation of the FOXP3 TSDR. On the other hand, patients with chronic microbial infections had significantly lower FOXP3 TSDR mean melting temperature (demethylated) when compared with healthy controls (78.28 ± 0.21 vs 78.44 ± 0.25, p < 0.05). Our results suggest that the use of HRM-PCR to detect FOXP3 TSDR methylation status is a reliable and easy method to predict natural regulatory T cell levels in peripheral blood in different disease conditions. Determining FOXP3 TSDR methylation status can be a useful tool in diagnosis, and monitoring the severity of autoimmune diseases and chronic microbial infections.
authors.affiliation: Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenetics , Changsha, Hunan , PR China .
authors.forename: Owen
authors.initials: O
authors.lastname: Ngalamika
authors.forename: Gongping
authors.initials: G
authors.lastname: Liang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Xinhai
authors.initials: X
authors.lastname: Yu
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Heng
authors.initials: H
authors.lastname: Yin
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Susan
authors.initials: S
authors.lastname: Yung
authors.forename: Tak Mao
authors.initials: TM
authors.lastname: Chan
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Lu
mesh_terms: D000328:Adult; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000235:genetics*; D015415:Biomarkers; D002908:Chronic Disease; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D007239:Infections / Q000175:diagnosis / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000235:genetics; D008875:Middle Aged; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: Autoimmune diseases; FOXP3 TSDR; HRM-PCR; chronic microbial infections; psoriasis; regulatory T cells; systemic lupus erythematosus