title: Increase of IRF-1 gene expression and impairment of T regulatory cells suppression activity on patients with myelodysplastic syndrome: A longitudinal one-year study.
abstract: Studies have demonstrated that abnormalities in interferon regulatory factor-1 (IRF-1) expression might develop myelodysplastic syndromes (MDS). IRF-1 was described as modulator of T regulatory (Treg) cells by suppressing Foxp3 on mice. We aimed to determine the role of Treg and IRF-1 in MDS. Thirty-eight MDS patients fulfilling WHO criteria and classified according to risk scores were evaluated at time 0 (T0) and after 12 months (T12) for: Treg suppression activity in coculture with T effector (Teff) cells; IRF-1 and Foxp3 genetic expression by qRT-PCR; IL-2, -4, -6, -10, -17, TNFα and IFNγ production by Cytometric Bead Array. No differences in Foxp3 expression (T0=0.06±0.06 vs T12=0.06±0.12, p=0.5), Treg number (T0=5.62±2.84×105vs T12=4.87±2.62×105; p=0.3) and Teff percentage (T0=16.8±9.56% vs T12=13.1±6.3%; p=0.06) were observed on T12. Low risk MDS patients showed a higher number of Treg (5.2±2.6×105) versus high risk group (2.6±1.2×105, p=0.03). Treg suppression activity was impaired on T0 and T12.Cytokine production and IRF-1 expression were increased on T12. The correlation between IRF-1 and FoxP3 was negative (r2=0.317, p=0.045) on T0. These results suggest a hyper activity of the immune system, probably secondary to Treg suppression activity impairment. This state may induce the loss of tolerance culminating in the proliferation of MDS clones.
authors.affiliation: Division of Hematology, Federal University of São Paulo, São Paulo, SP, Brazil; Fleury Group, Research and Development, São Paulo, SP, Brazil. Electronic address: asborgo@hotmail.com.
authors.forename: Aline S B
authors.initials: AS
authors.lastname: Perazzio
authors.affiliation: Division of Hematology, Federal University of São Paulo, São Paulo, SP, Brazil; Division of Hematology, Hospital Santa Marcelina, São Paulo, SP, Brazil.
authors.forename: José Salvador R
authors.initials: JS
authors.lastname: Oliveira
authors.affiliation: Division of Hematology, Instituto de Assistência Médica ao Servidor Público Estadual, São Paulo, Brazil.
authors.forename: Vera L P
authors.initials: VL
authors.lastname: Figueiredo
authors.affiliation: Division of Hematology, Federal University of São Paulo, São Paulo, SP, Brazil; Fleury Group, Research and Development, São Paulo, SP, Brazil.
authors.forename: Maria de Lourdes L F
authors.initials: ML
authors.lastname: Chauffaille
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D015870:Gene Expression; D006801:Humans; D007108:Immune Tolerance; D050856:Interferon Regulatory Factor-1 / Q000096:biosynthesis* / Q000502:physiology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D013997:Time Factors; D055815:Young Adult
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1
keywords: Foxp3; IRF-1; Immune system; Myelodysplastic syndrome; T regulatory cells; Treg