Regulatory T Cells from Patients with Rheumatoid Arthritis Are Characterized by Reduced Expression of Ikaros Zinc Finger Transcription Factors

Dittrich-Salamon, Mara; Meyer, Anja; Yan, Shuaifeng; Steinbach-Knödgen, Eva; Kotschenreuther, Konstantin; Stahl, David; Pesch, Carola tho; Schiller, Joanna; Byrtus, Franziska; Jochimsen, Dorothee; Golumba-Nagy, Viktória; Kofler, David M.

doi:10.3390/cells11142171

Cited by 5 publications

(4 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IKZF3 (Aiolos) and IKZF2 (Helios), and BACH2 have been implicated in other autoimmune disease such as systemic lupus erythematosus (SLE) and Rheumatoid Arthritis (RA) [25,[31][32][33][34][35][36]. In this study, the expression of these genes was increased in severe cases of CFS and greater upregulation was observed in those who suffer from comorbid autoimmune diseases, suggesting that CFS is, in part, an autoimmune disease.…”

Section: Cfs and T Cell And B Cell Functionsmentioning

confidence: 85%

Autoimmune gene expression profiling of fingerstick whole blood in Chronic Fatigue Syndrome

et al. 2022

View full text Add to dashboard Cite

Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition that can lead to severe impairment of physical, psychological, cognitive, social, and occupational functions. The cause of ME/CFS remains incompletely understood. There is no clinical diagnostic test for ME/CFS. Although many therapies have been used off-label to manage symptoms of ME/CFS, there are limited, if any, specific therapies or cure for ME/CFS. In this study, we investigated the expression of genes specific to key immune functions, and viral infection status in ME/CFS patients with an aim of identifying biomarkers for characterization and/or treatment of the disease. Methods In 2021, one-hundred and sixty-six (166) patients diagnosed with ME/CFS and 83 healthy controls in the US participated in this study via a social media-based application (app). The patients and heathy volunteers consented to the study and provided self-collected finger-stick blood and first morning void urine samples from home. RNA from the fingerstick blood was tested using DxTerity’s 51-gene autoimmune RNA expression panel (AIP). In addition, DNA from the same fingerstick blood sample was extracted to detect viral load of 4 known ME/CFS associated viruses (HHV6, HHV7, CMV and EBV) using a real-time PCR method. Results Among the 166 ME/CFS participants in the study, approximately half (49%) of the ME/CFS patients reported being house-bound or bedridden due to severe symptoms of the disease. From the AIP testing, ME/CFS patients with severe, bedridden conditions displayed significant increases in gene expression of IKZF2, IKZF3, HSPA8, BACH2, ABCE1 and CD3D, as compared to patients with mild to moderate disease conditions. These six aforementioned genes were further upregulated in the 22 bedridden participants who suffer not only from ME/CFS but also from other autoimmune diseases. These genes are involved in T cell, B cell and autoimmunity functions. Furthermore, IKZF3 (Aiolos) and IKZF2 (Helios), and BACH2 have been implicated in other autoimmune diseases such as systemic lupus erythematosus (SLE) and Rheumatoid Arthritis (RA). Among the 240 participants tested with the viral assays, 9 samples showed positive results (including 1 EBV positive and 8 HHV6 positives). Conclusions Our study indicates that gene expression biomarkers may be used in identifying or differentiating subsets of ME/CFS patients having different levels of disease severity. These gene targets may also represent opportunities for new therapeutic modalities for the treatment of ME/CFS. The use of social media engaged patient recruitment and at-home sample collection represents a novel approach for conducting clinical research which saves cost, time and eliminates travel for office visits.

show abstract

Section: Cfs and T Cell And B Cell Functionsmentioning

confidence: 85%

Autoimmune gene expression profiling of fingerstick whole blood in Chronic Fatigue Syndrome

et al. 2022

View full text Add to dashboard Cite

show abstract

“…IKZF3 is a member of the IKAROS family and plays an important role in the maturation of B and T cells, [9,10] it has been reported in hematopoietic malignancies, immunological diseases, and solid tumors. [11][12][13][14] However, the association of IKZF3 expression with HNSCC has not been reported. This is the first study to explore the prognostic value of IKZF3 expression in HNSCC.…”

Section: Discussionmentioning

confidence: 99%

“…Aiolos is a zinc finger transcription factor (TF), encoded by IKZF3, that has a broad impact on gene expression patterns by activating chromatin modifiers like nucleosome remodeling and deacetylase complexes. [9,10] In more recent years, the crucial value of IKAROS family zinc finger members (IKZF) has been increasingly recognized in immune diseases and solid tumors, [11,12] and research in hematopoietic malignancies has been initially identified as evidence for the participation of the IKAROS family in carcinoma progression. [13,14] Mounting evidence suggests that the immune system plays a crucial role in tumorigenesis, growth, and metastasis, and immune-related genes are believed to be associated with tumor prognosis.…”

Section: The Study Was Funded By Basic Public Welfare Project Of Ning...mentioning

confidence: 99%

IKZF3 is a novel prognostic biomarker for head and neck squamous cell carcinoma: A study based on bioinformatics analysis

et al. 2023

Medicine

View full text Add to dashboard Cite

In the past few years, immunotherapy of tumors has become an extensive research hotspot, and the value of IKZF family genes in the tumor microenvironment has also been increasingly recognized. However, the expression of the IKAROS family zinc finger 3 (IKZF3) gene in human head and neck squamous cell carcinoma (HNSCC) and its prognostic value were not reported for the main subset until now. In the present study, we analyzed the relationship between IKZF3 gene expression and the survival of HNSCC patients. To evaluate the potential of IKZF3 as a prognostic biomarker for HNSCC comprehensively, multiple online analysis tools, including UALCAN, cBioPortal, GEPIA, WebGestalt, String, Genomic Data Commons, and TIMER databases were utilized in our study. We observed that the HNSCC patients with higher IKZF3 expression tended to exhibit longer overall survival. Univariate and multivariate Cox regression analyses indicated that age and grade were independent prognostic indicators in HNSCC. Moreover, Gene Ontology and KEGG function enrichment analyses showed that several pathways in HNSCC might be pivotal pathways regulated by IKZF3, which revealed that IKZF3 was probably participating in the occurrence and development of HNSCC. Furthermore, the hypomethylation of the IKZF3 gene was closely associated with genes that observed mutation in HNSCC. IKZF3 was significantly correlated with several immune cells in HNSCC (e.g., CD8+ T cell, CD4+ cell, and dendritic cell). We explored the potential prognostic values and roles of the IKZF3 in HNSCC, revealing that IKZF3 was probably a novel and reliable prognostic biomarker for patients with HNSCC.

show abstract

“…IKZF3 (Aiolos) and IKZF2 (Helios), and BACH2 have been implicated in other autoimmune disease such as systemic lupus erythematosus (SLE) and Rheumatoid Arthritis (RA) [22,[28][29][30][31][32][33].…”

Section: Cfs and T Cell And B Cell Functionsmentioning

confidence: 99%

Autoimmune Gene Expression Profiling of Fingerstick Whole Blood in Chronic Fatigue Syndrome

Wang

Waldman

Basavanhally

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition that can lead to severe impairment of physical, psychological, cognitive, social, and occupational functions. The cause of ME/CFS remains incompletely understood. There is no clinical diagnostic test for ME/CFS. Although many therapies have been used off-label to manage symptoms of ME/CFS, there are limited, if any, specific therapies or cure for ME/CFS. In this study, we investigated the expression of genes specific to key immune functions, and viral infection status in ME/CFS patients with an aim of identifying biomarkers for characterization and/or treatment of the disease. Methods In 2021, one-hundred and sixty-six (166) patients diagnosed with ME/CFS and 83 healthy controls in the US participated in this study via a social media-based application (app). The patients and heathy volunteers consented to the study and provided self-collected finger-stick blood and first morning void urine samples from home. RNA from the fingerstick blood was tested using DxTerity’s 51-gene autoimmune RNA expression panel (AIP). In addition, DNA from the same fingerstick blood sample was extracted to detect viral load of 4 known ME/CFS associated viruses (HHV6, HHV7, CMV and EBV) using a real-time PCR method. Results Among the 166 ME/CFS participants in the study, approximately half (49%) of the ME/CFS patients reported being house-bound or bedridden due to severe symptoms of the disease. From the AIP testing, ME/CFS patients with severe, bedridden conditions displayed significant increases in gene expression of IKZF2, IKZF3, HSPA8, BACH2, ABCE1 and CD3D, as compared to patients with mild to moderate disease conditions. These six aforementioned genes were further upregulated in the 22 bedridden participants who suffer not only from ME/CFS but also from other autoimmune diseases. These genes are involved in T cell, B cell and autoimmunity functions. Furthermore, IKZF3 (Aiolos) and IKZF2 (Helios), and BACH2 have been implicated in other autoimmune diseases such as systemic lupus erythematosus (SLE) and Rheumatoid Arthritis (RA). Among the 240 participants tested with the viral assays, 9 samples showed positive results (including 1 EBV positive and 8 HHV6 positives). Conclusions Our study indicates that gene expression biomarkers may be used in identifying or differentiating subsets of ME/CFS patients having different levels of disease severity. These gene targets may also represent opportunities for new therapeutic modalities for the treatment of ME/CFS. The use of social media engaged patient recruitment and at-home sample collection represents a novel approach for conducting clinical research which saves cost, time and eliminates travel for office visits.

show abstract

Regulatory T Cells from Patients with Rheumatoid Arthritis Are Characterized by Reduced Expression of Ikaros Zinc Finger Transcription Factors

Cited by 5 publications

References 47 publications

Autoimmune gene expression profiling of fingerstick whole blood in Chronic Fatigue Syndrome

Autoimmune gene expression profiling of fingerstick whole blood in Chronic Fatigue Syndrome

IKZF3 is a novel prognostic biomarker for head and neck squamous cell carcinoma: A study based on bioinformatics analysis

Autoimmune Gene Expression Profiling of Fingerstick Whole Blood in Chronic Fatigue Syndrome

Contact Info

Product

Resources

About