title: Increased Levels of STAT1 Protein in Blood CD4 T Cells from Systemic Lupus Erythematosus Patients Are Associated with Perturbed Homeostasis of Activated CD45RA-FOXP3hiRegulatory Subset and Follow-Up Disease Severity.
abstract: In murine systemic lupus erythematosus (SLE), aberrant regulation of interferon (IFN)-alpha-STAT1 signaling and perturbed homeostasis of CD4+FOXP3+regulatory T cells (Tregs) were described. In the present study, STAT1 signaling and circulating Treg subsets were assessed by flow cytometry in 39 SLE patients and their potential association with disease course was examined during long-term follow-up. Levels of STAT1 protein as measured by median fluorescence intensity (MFI) were significantly increased in SLE CD4 T cells when compared with rheumatoid arthritis patients and healthy controls and were positively correlated with disease activity. The highest STAT1 MFI was found in CD45RA-FOXP3hi-activated Treg (aTreg) subset, which demonstrated the highest STAT1 phosphorylation responses among SLE CD4 T cells and significant decrease in proliferation marker Ki-67 expression after IFN-alpha stimulation. Percentage of Ki-67+aTregs was significantly decreased in SLE patients and was negatively correlated with CD4 T cell STAT1 MFI. A subgroup of SLE patients characterized by lower aTreg counts experienced more severe relapsing disease course during 1,000 days of follow-up. Mean CD4 T cell STAT1 MFI in follow-up samples from SLE patients was negatively correlated with mean of follow-up aTreg counts. Our findings indicate that augmented STAT1 signaling may be involved in perturbed aTreg homeostasis, which could represent a possible marker of SLE disease severity.
authors.affiliation: 1 Department of Laboratory Diagnostics, University Medical Centre Maribor , Maribor, Slovenia .
authors.forename: Aleš
authors.initials: A
authors.lastname: Goropevšek
authors.affiliation: 1 Department of Laboratory Diagnostics, University Medical Centre Maribor , Maribor, Slovenia .
authors.forename: Maksimiljan
authors.initials: M
authors.lastname: Gorenjak
authors.affiliation: 2 Department of Rheumatology, University Medical Centre Maribor , Maribor, Slovenia .
authors.forename: Suzana
authors.initials: S
authors.lastname: Gradišnik
authors.affiliation: 2 Department of Rheumatology, University Medical Centre Maribor , Maribor, Slovenia .
authors.forename: Klara
authors.initials: K
authors.lastname: Dai
authors.affiliation: 2 Department of Rheumatology, University Medical Centre Maribor , Maribor, Slovenia .
authors.forename: Iztok
authors.initials: I
authors.lastname: Holc
authors.affiliation: 3 Department of Nephrology, University Medical Centre Maribor , Maribor, Slovenia .
authors.forename: Radovan
authors.initials: R
authors.lastname: Hojs
authors.affiliation: 4 Faculty of Medicine, University of Maribor , Maribor, Slovenia .
authors.forename: Ivan
authors.initials: I
authors.lastname: Krajnc
authors.affiliation: 2 Department of Rheumatology, University Medical Centre Maribor , Maribor, Slovenia .
authors.forename: Artur
authors.initials: A
authors.lastname: Pahor
authors.affiliation: 5 Department of Allergology, Rheumatology and Clinical Immunology, University Children's Hospital, University Medical Center Ljubljana , Ljubljana, Slovenia .|6 Faculty of Medicine, University of Ljubljana , Ljubljana, Slovenia .
authors.forename: Tadej
authors.initials: T
authors.lastname: Avčin
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000494:pharmacology; D019394:Ki-67 Antigen / Q000235:genetics / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D061251:Primary Cell Culture; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology*; D012720:Severity of Illness Index; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016898:Interferon-alpha; D019394:Ki-67 Antigen; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D017493:Leukocyte Common Antigens
keywords: IFNs and cytokines: autoimmunity and inflammation; JAK/STAT; T-cells