scholarly journals Relation of interleukin-1β gene to treatment response in chronic patients infected with HCV genotype 4

2013 ◽  
Vol 7 (11) ◽  
pp. 851-858 ◽  
Author(s):  
Moataza Hassan Omran ◽  
Noha E. Ibrahim ◽  
Samar S. Youssef ◽  
Basma E Fatouh ◽  
Wael Nabil ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Interferon Therapy ◽  
Strong Association ◽  
Response To Therapy ◽  
Interleukin 1Β ◽  
Response To Treatment ◽  
P Value ◽  
Chronic Patients ◽  
Genotype 4 ◽  
Chronic Hcv

Introduction: Hepatitis C virus (HCV) infection results in chronic hepatitis in more than 70% of infected patients, while 20-30% of patients recover spontaneously. This strengthens the role of the host genetic factors in either spontaneous or drug-induced viral clearance. The aim of this study was to investigate the relationship between interleukin-1β +3953 gene polymorphism and the response to interferon therapy in chronic HCV patients infected with genotype 4. Methodology: The interleukin-1β (+3953 C/T) (rs1143634) gene was amplified in 115 chronic HCV patients. Interleukin-1β single nucleotide polymorphism (SNP) plus several clinical and pathological factors were statistically analyzed in correlation with response to therapy. Results: Genotypes C/T and T/T had a significant association with non-response to treatment compared to genotype C/C, which had a strong association with response to treatment (95% confidence; 6.4884-48.5818, p = 0.0001). Furthermore, analysis of allele frequency in this cohort revealed that the T allele is associated with non-response, higher fibrosis, and higher hepatic activity, while the C allele had a significant association with sustained virologic response lower fibrosis, and lower hepatic activity (p value = 0.0001). Conclusion: This is the first study to examine the correlation between interleukin-1β (+3953 C/T) (rs1143634) gene polymorphism and the response of interferon therapy in genotype 4 HCV-infected patients. The results encourage further assessment of this SNP as a marker  to predict response to therapy and disease progression, which can have major implications in saving money, time, and in avoiding unnecessary adverse effects.

scholarly journals Vitamin D Receptor FokI Gene Polymorphism Predicted Poor Response to Treatment in Chronic HCV Genotype 4

2016 ◽  
Vol 6 (4) ◽  
pp. 265-270 ◽  
Author(s):  
Hany Shehab ◽  
◽  
Dina Sabry ◽  
Mai Mukhtar ◽  
Wafaa Elakel ◽  
...  
Keyword(s):  
Vitamin D ◽  
Gene Polymorphism ◽  
Vitamin D Receptor ◽  
Poor Response ◽  
Response To Treatment ◽  
Genotype 4 ◽  
Hcv Genotype ◽  
Chronic Hcv

IL‐28β gene polymorphism determines virological response to PEGylated interferon therapy in hepatitis C virus genotype 4 Egyptian patients

2018 ◽  
Vol 120 (5) ◽  
pp. 8154-8159 ◽  
Author(s):  
Nashwa El‐Khazragy ◽  
Naglaa El Sayed ◽  
Ahmed M. Salem ◽  
Nahla S. Hassan ◽  
Amal Tohamy Abdelmoeaz ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Gene Polymorphism ◽  
Virological Response ◽  
Interferon Therapy ◽  
Pegylated Interferon ◽  
Virus Genotype ◽  
Genotype 4 ◽  
Egyptian Patients

scholarly journals P1795ASSOCIATION BETWEEN T CELL INFILTRATION IN BIOPSY PROVEN ACUTE T CELL MEDIATED REJECTION AND RESPONSE TO THERAPY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Nooshin Dalili ◽  
Pedram Ahmadpoor ◽  
Behzad Einollahi ◽  
Hamed Azhdari Tehrani
Keyword(s):  
T Cell ◽  
Graft Function ◽  
Stable Condition ◽  
Response To Therapy ◽  
Response To Treatment ◽  
P Value ◽  
Organ Rejection ◽  
Graft Outcome ◽  
Significant Difference

Abstract Background and Aims Renal transplantation is considered as the best replacement therapy for advanced ESRD patients. An allograft rejection happens as a result of post transplant immune reactions, which change the outcome of the organ transplantation. Today a major challenge in the field of transplantation is the identification of easy, reliable and non-invasive markers or methods that being able to predict the probability of organ rejection. One of the possible methods is looking for type of infiltrated cells in tissue obtaining by biopsy stained with specific cellular markers and assesses the infiltration of these cells in different types of rejection. Here the severity of CD3, CD20, Th17 and FOXP3 infiltration in patients with biopsy proven acute cellular rejection was evaluated based on IHC staining, whether these specific infiltrations can show an association with graft outcome or not. Method 50 patients with biopsy proven Acute T Cell Mediated Rejection (ATCMR) recruited. Previous clinical data and 1 year clinical follow up collected. The entire specimen assessed for infiltration of CD3, CD20, FOXP3 Tregs and Th17 with IHC. Patients divided into subgroups: stable graft function versus impaired graft function based on serum creatinine course in one year follow up after rejection therapy and appropriate response to treatment versus failure to response, based on allograft function throughout the course of admission. Results In impaired graft function arm, FOXP3 (7.88 vs. 8.02 with P-value 0.96) and Th17 cells were higher (5.01 vs. 10.2 with P-value 0.24) but with non-significant values. FOXP3/Th17 ratio was higher in stable group (1.4 vs. 1.12 with P-value 0.22). In failure to response to therapy group both FOXP3 (9.95 vs. 6.63 with P-value 0.1) and Th17 (11.3 vs. 8.3 with P-value 0.15) cells were higher. FOXP3/Th17 ratio was higher in proper response group (1.19 vs. 1.15 with P-value 0.8). No significant difference was obtained between CD3 and CD20 infiltration in these two groups. Conclusion Final results showed that Th17 has more important role in predicting the graft outcome and response to treatment and FOXP3 infiltration had a minor part. This may be in controversial with previous facts about the role of FOXP3 cells, which drive the allograft into stable condition.

Gender as a Prognostic Factor in CLL. Biological Pointers to the Improved Outcome of Women.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 957-957 ◽  
Author(s):  
Daniel Catovsky ◽  
Estella Matutes ◽  
Alison Morilla ◽  
Anna Burford ◽  
Vasantha Brito-Babapulle ◽  
...  
Keyword(s):  
Cox Regression ◽  
Randomised Trial ◽  
Lower Proportion ◽  
Response To Therapy ◽  
Response To Treatment ◽  
P Value ◽  
Fish Analysis ◽  
Randomised Trials ◽  
Cox Regression Analysis ◽  
Mutational Status

Abstract Gender is not widely regarded as a prognostic indicator in CLL. However, the combined data from three MRC randomised trials, CLL1, 2 and 3, and two observational studies for patients with Binet stage A, CLL2A and 3A, over a period of 20 years (1978-1998) totalling 2370 patients, showed a significant survival advantage for women (2p<0.0001). Cox regression analysis of the three randomised trials showed that gender, age, stage and response to therapy were independent prognostic variables. The response to treatment for women was also better than for men receiving the same therapies. The LRF CLL4 randomised trial, which started in 1999 shows the same trend. Preliminary results in 444 patients Binet stages A progressive, B and C showed the same CR/Nod.PR for both sexes (43.5%) but a higher PR rate in women (45%) vs men (36.5%) and a lower proportion of women non-responders to first line therapy (11.5% vs 20%). A number of laboratory investigations in CLL4, which included FISH analysis with five probes, VH mutational status, CD38 and ZAP-70 expression by flow cytometry, showed differences between the sexes, which were significant for 17p and 11q deletions combined and CD38, always in favour of women, as shown in Tables 1 and 2. The clinical and laboratory results suggest that CLL is biologically more benign in women. Women have a lower incidence of CLL, an overall higher incidence of stage A (41.7%) than men (27.3%) in CLL 1, 2, 2A, 3 and 3A and respond better to treatment in all the trials. These differences may be underlined by a higher proportion of 13q del as sole abnormality, a lower proportion of 17p (p53 locus) and 11q deletions and lower levels of CD38. Data on VH mutations and ZAP-70 point in the same direction but the number of cases studied is still small. An additional factor that may play a role in the better outcome for women relates to the effect of oestrogen derivatives which are known to target selectively superoxide dismutase and induce cell kill (Huang et al, Nature407, 390, 2000). Table 1: FISH analysis by gender (Dohner hierarchical model) Abnormality 17p del 11q del Trisomy 12 13q del Others * = Combined p value < 0.05 (Chi-Square test) Men (286) 12% 19% 10% 34% 25% Women (94) 7% 13% 11% 44% 25% p value * * 0.052 Table 2: Other biological markers CD38 negative (<30%) VH mutated ZAP-70 negative Men 173/335 (52% ) 51/149 (34%) 94/192 (49%) Women 68/100 (68%) 23/52 (44%) 42/68 (62 %) p value <0.005 NS 0.07

Response to Therapy and Survival in CLL Is Influenced by Genetic Markers. Preliminary Analysis from the LRF CLL4 Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 13-13 ◽  
Author(s):  
Daniel Catovsky ◽  
Sue Richards ◽  
Estella Matutes ◽  
Anna Burford ◽  
Vasantha Brito-Babapulle ◽  
...  
Keyword(s):  
Response To Therapy ◽  
Response To Treatment ◽  
Critical Threshold ◽  
P Value ◽  
Fish Analysis ◽  
Chi Square ◽  
Clear Trend ◽  
First Line Therapy ◽  
Genetic Abnormalities ◽  
Trisomy 12

Abstract The randomised CLL4 trial was launched in 1999 to answer scientific and management issues. Since then, 730 patients with Binet stages A progressive, B and C have been randomised between 1) chlorambucil (10mg/m2 x 7 days), or 2) fludarabine (FDR) alone (40mg/m2 x 5 d oral or 25mg/m2 x 5 days IV), or FDR plus cyclophosphamide (FDR 24mg/m2 x 5 d oral or 25mg/m2 x 3 d IV plus cyclo 150mg/m2 x 5 d oral or 250mg/m2 x 3 d IV). Information on FISH analysis with 5 probes is available on 440 patients. The incidence of the genetic abnormalities is: 13q del (60%), trisomy 12 (15%), 6q del (8%), 11q del (19%), 17p del (11%); some markers are positive in more than one patient. Analysis by stage showed no differences in the distribution of these markers and analysis by age showed that patients with 13q del were younger (p=0.006) and those with 11q del were older (p=0.01). Analysis by response to all therapies (as the code of individual therapies has not been broken) in 343 patients is shown in Table 1. The results show clearly that almost half the patients with 17p del (p53 locus) are primary non-responders (NR) or show progressive disease (PD) following first line therapy, and have poor survival. 2yr survival of patients with none of these abnormalities was 87% (79%–95%), and using a hierarchical model with normals as the fifth group there was a clear trend in survival between groups (2p<0.00005). When the % of 17p del lymphocytes was correlated with response, it was apparent that the higher the % of 17p del cells the greater the proportion of non-responders (Table 2), with 20% 17p del being the critical threshold. When we grouped together cases with 6q, 11q and 17p deletion plus trisomy 12 (representing 42% of cases) there was a significantly lower response rate compared with the cases without those four abnormalities: CR/Nod PR 35% vs 47%, PR 33% vs 39%, and 32% vs 13%, (Chi-square 13.3; p=0.0003). This study demonstrates that the genetic abnormalities which can be shown in c.80% of patients with active CLL have a significant bearing on the response to treatment and early survival, confirming the survival differences reported by Dohner at al (N Engl J Med 343: 1910–16; 2000). It remains to be determined whether better therapies could overcome the low response rates of patients with poor prognostic genetic abnormalities. Table 1: FISH analysis by response (non-hierarchical) and survival Abnormality CR/Nod PR PR NR/PD p value* 2 yr survival (95% CI) * Analysis of individual abnormalities versus the rest; Chi-square test; **326 patients 17p del 33% 18% 48% 0.004 67% (50%–85%) 11q del 29% 44% 27% NS 73% (59%–86%) Trisomy 12 41% 31% 29% NS 72% (57%–87%) 6q del** 39% 29% 32% NS 75% (56%–95%) 13q del 42% 37% 21% NS 91% (86%–95%) Table 2: Correlation of response with proportion of 17p del lymphocytes % deletion No. cases CR/Nod PR PR NR/PD Chi-square 318.8; p<0.0001 <5 (negative) 310 43% 39% 18% 5–20 18 61% 22% 17% >20–100 15 0% 13% 87%

A Distinct Immunophenotypic Profile Of Del(5q) MDS Allows For Fast Monitoring Of Response To Treatment With Lenalidomide Or Azacitidine

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2780-2780
Author(s):  
Uta Oelschlaegel ◽  
Brigitte Mohr ◽  
Michael Kramer ◽  
Stefani Parmentier ◽  
Katja Sockel ◽  
...  
Keyword(s):  
Tp53 Mutation ◽  
Mutational Analysis ◽  
Conflicts Of Interest ◽  
Strong Association ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Response Monitoring ◽  
Minor Role ◽  
Disease Modifying Drugs ◽  
Disease Modifying

Abstract Introduction Patients with MDS harboring a del(5q) often display characteristic morphological features in the bone marrow. For the first time we have recently demonstrated a strong association of the presence of a cytogenetic abnormality - del(5q) - with a specific 5-parameter immunophenotypic profile measured by flow cytometry (FCM). The aim of this prospective study was to test, if this FCM profile could also be applied for monitoring response to treatment with disease-modifying drugs like lenalidomide and azacitidine. Patients and methods Overall, 137 FCM investigations were performed in 52 well-characterized patients with MDS and a del(5q) (IPSS low/int-1: n=30, int-2/high: n=22) including 34 patients with isolated del(5q): 53 measurements before treatment and 84 during treatment (lenalidomide=47 and/or azacitidine=35; chemotherapy and/or allogeneic transplantation=6). Nineteen of 41 thereupon evaluated patients showed a concomitant TP53 mutation. An 8-color/5-tube FCM diagnostic procedure (lyse-stain-wash) was performed on a FACS-Canto II cytometer. Thus, the typical del(5q) FCM profile includes the following 5 parameters: percentage of myeloid progenitors (myPC > 2%) = 3 points, CD45 MFI ratio (lymphocytes : myPC ≤ 7.0) = 10 points, SSC ratio (granulocytes : lymphocytes < 6.0) = 2 points, CD71 (≤ 20%) on granulocytes = 1.5 points, and female gender = 1.5 points. The weighting of these parameters has been done using a logistic regression model. Results In 48/53 (92%, mean score=16.5±2.0) of the FCM measurements before therapy del(5q) was predictable with the 5-parameter FCM score. In the few FCM inconclusive cases the mutational analysis showed a TP53 mutation. Remarkably, in all 18 cases being in cytogenetic complete remission (CCR) in response to therapy the disappearance of del(5q) by conventional cytogenetic analyses was accompanied by the disappearance of the del(5q) FCM profile (specificity=100%; mean score=13.0±1.0). On the other hand, in patients without CCR during treatment the presence of del(5q) could be predicted by the FCM-score (≥ 15) with a sensitivity of 65% (43/66; mean score=15.5±3.0). Of note, in most of those inconclusive measurements (85%) a mutation of the TP53 gene and/or a deletion of chromosome (17p) could be detected suggesting a modification of the immunophenotype mediated by these molecular changes. Interestingly, the complexity of karyotypic abnormalities appeared to play a minor role in modifying the immunophenotype because in two-thirds of the FCM inconclusive cases del(5q) was present as a single abnormality. Conclusion The proposed 5-parameter del(5q) FCM profile can serve as a surrogate for the presence of a del(5q) and could therefore be used as a rapid tool for response monitoring during treatment with disease-modifying drugs. The role of TP53 mutations in modifying the FCM-profile in this context should be the purpose of further investigations. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Association of GSTP1 Ile-105-Val Gene Polymorphism with Response to Treatment Among Iraqi Chronic Myeloid Leukaemia Patients

2018 ◽  
pp. 133-141
Keyword(s):  
Gene Polymorphism ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Chronic Phase ◽  
Potential Effect ◽  
Response To Treatment ◽  
P Value ◽  
Log Reduction ◽  
Functional Polymorphisms ◽  
Polymorphic Variants

Background: Pharmacogenomics is a relatively new study field that synergize pharmacology with genomics, analyzing the correlation between genetic variation and pharmacokinetics among patients. In the current study, we evaluated the potential effect of functional polymorphisms within gene encoding for Glutathione S transferase pi class (GSTPs) and treatment response among chronic myeloid leukaemia) CML) patients. GSTPs are multifunctional phase II biotransformation enzymes. Their main biologic role is to catalyze the conjugation to endogenous glutathione (GSH). In addition, they can alter drug potency in malignant cells. Polymorphic variants of these enzymes have been implicated in inter-patients' variability in drug response and outcome in CML patients. Aim of study: Evaluating the association between GSTP1 Ile-105-Val gene polymorphism and response to treatment among Iraqi CML patients. Method: A ‘PCR-RFLP’ assay was implemented to detect the polymorphic variants of codon 105 GSTP1 gene of forty Iraqi CML patients in chronic phase referring to the National Center of Haematology in the period between November 2017 and July 2018. Results: Our result revealed a statistically significant association between the GSTP1 genotypes and response to treatment. The variant genotypes were associated with inferior log reduction in BCR-ABL1 mRNA and poorer responses comparing to the wild genotype with P-value of 0.006, and 0.034 respectively.

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