TGFβ and IL10 Have an Impact on Risk Group and Prognosis in Childhood ALL

Abstract Introduction: Considering that cytokines play an important role in immune response and that many infectious, autoimmune and malignant diseases are influenced by cytokine production, we hypothesized that genetically determined cytokine gene polymorphism might have an important influence on prognosis in pediatrics acute lymphoblastic leukemia (ALL). Methods: In this study, 95 pediatric ALL-patients were examined with regard to cytokine gene polymorphisms (TNFα, TGFβ, IL10 and IFNγ) and their potential association with prognosis. Moreover we analyzed the intracellular production of theses cytokines in patient T-cells. Results: TGFβ high-producer-haplotypes were associated with high-risk ALL-patients (Codon 10: T/T) and with the tendency of a reduced overall survival, whereas IL10 high-producer-genotypes were associated with a reduced relapse rate and a superior overall survival compared to IL-10-low-producer patients. Gene-polymorphisms of the pro-inflammatory cytokines IFNγ and TNFα did not show an impact on prognosis and risk-group of ALL in our cohort. On a functional basis TNFα and IFNγ expression of T-cells at initial diagnosis was significantly reduced in high-risk- and T-ALL-patients in comparison to healthy controls. Summary: Cytokine gene-polymorphisms of the regulatory/anti-inflammatory cytokines TGFβ and IL10, but not of the pro-inflammatory cytokines IFNγ and TNFα seem to have an impact on prognosis of pediatric ALL patients. Reduced capacity to produce pro-inflammatory cytokines at diagnosis may serve as a functional risk factor. These data may help in further risk stratification and adaptation of therapy-intensity. Disclosures No relevant conflicts of interest to declare.

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Association of a Large Panel of Cytokine Gene Polymorphisms with Complications and Comorbidities in Type 2 Diabetes Patients

Journal of Diabetes Research ◽

10.1155/2015/605965 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 17

Author(s):

K. F. Rodrigues ◽

N. T. Pietrani ◽

V. C. Sandrim ◽

C. M. A. F. Vieira ◽

A. P. Fernandes ◽

...

Keyword(s):

Type 2 Diabetes ◽

Diabetic Retinopathy ◽

Inflammatory Cytokines ◽

Gene Polymorphisms ◽

Microvascular Complications ◽

Cytokine Gene ◽

Large Panel ◽

Cytokine Gene Polymorphisms ◽

Diabetes Patients

Aims. The polymorphisms of pro- and anti-inflammatory cytokines may be involved in type 2 diabetes (T2D) pathogenesis and its complications.Methods. We investigated in 102 T2D patients the association of the cytokine polymorphisms in the TNF-α, IL-10, IL-6, TGF-β1, and IFN-γgenes with the T2D microvascular complications and comorbidities (hypertension, dyslipidemia, and obesity). Cytokine genotypes were determined by PCR using Cytokine Genotyping Tray kit.Results.Diabetic retinopathy was associated with GG genotype and G allele in TGF-β1 codon 25C/G polymorphism (p=0.004andp=0.018) and the nephropathy was associated the lower frequency of GG genotype in IL-10 -1082G/A polymorphism (p=0.049). Hypertension was associated with the CC genotype and C allele for IL-10 -592C/A polymorphism (p=0.013andp=0.009) and higher frequencies of T (p=0.047) and C (p=0.033) alleles of the TGF-β1 codon 10T/C and IL-10 -819T/C polymorphisms, respectively. The TGF-β1 codon 10T/C polymorphism was associated with the BMI groups (p=0.026): the CC genotype was more frequent in the group with BMI < 25 Kg/m2, while the TC genotype was more frequent in the group with BMI = 30 Kg/m2.Conclusions. Our findings suggest that TGF-β1 and IL-10 polymorphisms are involved in complications and comorbidities in T2D patients.

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The cytokine gene polymorphisms (TNF- and #945;, IL-10 And IFN- and #947;) and the role of inflammatory cytokines in diabetic neuropathy

International Journal of Research in Medical Sciences ◽

10.5455/2320-6012.ijrms20141142 ◽

2014 ◽

Vol 2 (4) ◽

pp. 1470 ◽

Cited By ~ 2

Author(s):

M Ramesh ◽

Konathala Kumari ◽

G Sudhakar

Keyword(s):

Diabetic Neuropathy ◽

Inflammatory Cytokines ◽

Gene Polymorphisms ◽

Cytokine Gene ◽

Cytokine Gene Polymorphisms

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Cytokine Gene Polymorphisms in Cancer and Inflammatory Disorders

Current Immunology Reviews ◽

10.2174/1573395514666180724121419 ◽

2018 ◽

Vol 14 (2) ◽

pp. 81-93

Author(s):

Hanim Kamis Norhalifah ◽

Nor Fazila Che Mat ◽

Hisham Atan Edinur

Keyword(s):

Gene Polymorphisms ◽

Cytokine Gene ◽

Inflammatory Disorders ◽

Cytokine Gene Polymorphisms

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FRI0550 CAN CYTOKINE GENE POLYMORPHISMS BE USEFUL FOR THE THERAPEUTIC CHOICE IN JAPANESE PATIENTS WITH RHEUMATOID ARTHRITIS?

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2067 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 876.2-877

Author(s):

S. Tsujimoto ◽

M. Shigesaka ◽

A. Tanaka ◽

Y. Ozaki ◽

T. Ito ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Autoimmune Disease ◽

Gene Polymorphisms ◽

Therapeutic Response ◽

Bone Erosion ◽

Japanese Patients ◽

Cartilage Degradation ◽

Cytokine Gene ◽

Biological Dmards ◽

Cytokine Gene Polymorphisms

Background:Rheumatoid arthritis (RA) is a common autoimmune disease. It is characterized by systemic synovitis with bone erosion and joint cartilage degradation(1). Production of autoantibody is important for autoimmune disease. Cytokines play crucial roles in its pathogenesis(2). SNP distribution varies between races. Few studies have examined SNP targeted at Japanese patients. The analysis of cytokine gene polymorphisms is important factor of pathophysiology and treatment.Objectives:This analysis was aimed to investigate the association between cytokine gene polymorphisms and autoantibody and therapeutic response in Japanese RA patients.Methods:This study subjects consisted of 100 RA patients and 50 healthy controls. We extracted data on patient sex, age, disease duration, rheumatoid factor (RF), anti cyclic citrullinated peptide (anti-CCP) antibody and therapeutic response including methotrexate (MTX) and biological DMARDs. Genomic DNA was isolated from peripheral blood, these were genotyped for TNFα, TGFβ1, IL-6, IL-10 and IFNγ polymorphisms. We analyzed these data using a chi-square test.Results:IL-10 (-819 C/T and -592 C/A) revealed that there were significant decrease in the frequency of IL-10 (-819) CC genotype and (-592) CC genotype as compared to controls in RA patients. Genotyping of IL-10 showed that there was significant decrease ACC/ACC genotype (Table 1).IFNγ (+874 A/T) revealed that there was significant decrease in the frequency of TT genotype as compared to controls (Table 1).No significant differences in TNFα, TGFβ1and IL-6 genotypes and alleles frequency were observed between RA patients and control.TGFβ1(+869 A/T) in patients with anti-CCP antibody positive revealed that there was significant decrease in the frequency of TT genotype as compared to patients with anti-CCP antibody negative (Table 2).No significant association between RF and any cytokine gene polymorphism.Analyzing cytokine gene polymorphisms could be useful for treatment with MTX and biological DMARDs.Table 1.Table 2.Conclusion:IL-10 (-819 C/T, -592 C/A) and IFNγ (+874 A/T) polymorphism might be related to RA in Japanese population. In addition, TGFβ1(+869 A/T) polymorphism might be associated with the production of anti-CCP antibody. These results suggest that the analyzing cytokine gene polymorphisms may offer promise as useful factors in the choice of treatment for Japanese RA patients.References:[1] Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet. 2010; 376: 1094–108.[2] McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007 Jun;7(6):429-42.Disclosure of Interests:None declared

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