Association of IL-17 gene polymorphisms and serum level with graft versus host disease after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Cytokines are important factors determining the outcome of transplantation. Host ability in cytokine production may be affected by cytokine genes polymorphisms. The aim of the present study was to investigate the effect of IL-17 gene polymorphisms on outcome of Hematopoietic stem cell transplantation. MATERIALS AND METHODS: A total of 60 bone marrow recipients were included in this study. Twenty-five recipients (41.66%) underwent a GVHD. IL-17 gene polymorphisms were evaluated by PCR-RFLP method and the serum levels were also checked by ELISA. RESULTS: No significant differences in distribution of the IL-17(A/G) (rs3819025) genotypes and alleles were observed between two groups. But, IL-17 (A/G, -197) GG genotype was found to be significantly higher in GVHD group compared to those of non-GVHD group (P = 0.04). Interestingly, after stratification of patients according severity of GVHD, IL-17 (rs3819025) G allele was remained significantly higher in GVHD grade (0-I) group compared to those of grade (II-IV) group (P = 0.05). In addition, after categorization of patients according to their sex, IL-17-197 GG genotype showed a significant association with non-GVHD in male patients (P = 0.05). IL-17 serum levels did not show any significant difference between GVHD and non GVHD groups. CONCLUSION: Results indicated that IL-17197 GG genotype, G allele of (rs3819025) and its serum level have predictive values for severity of GVHD. Also, IL-17-197 GG genotype is a sex dependent genetic risk factor for development of GVHD, but this subject need to be studied in different population.

Study of the relationships between IL-23R, IL-17, IL-21 polymorphisms and serum level of IL-17, IL-21 with acute graft rejection in iranian liver transplant recipients.

Cytokines are important factors determining the outcome of transplantation. Since host ability in cytokine production may be affected by cytokine genes polymorphisms, the aim of the present study was to investigate the effect of IL-17, IL-23R and IL-21 gene polymorphisms in outcome of liver transplantation. A total of 200 liver transplant recipients were included in this study. IL-17 -197 A/G, IL-21+1472 G/T, IL-21 5250 C/T, and IL-23R C/A polymorphisms were evaluated by PCR-RFLP or ARMS-PCR methods. The serum levels of IL-17 and IL-21 in rejected and non-rejected groups were determined by ELISA method. The results showed that IL-23R AC carriers and C allele were significantly more frequent in patients with acute rejection than patients without rejection (p=0.01 and p=0.0005, respectively). After gender classification, IL-23R AA and AC carriers were significantly more frequent in female patients (p=0.01, p=0.01, respectively) and IL-23R AA and AC carriers and A allele were significantly more frequent in male patients (p=0.009, p=0.02, p=0.003, respectively). There is a significant association between CC genotype and C alleles of IL-23R and AR in the patients receiving allograft from living donor (p=0.0003 and p=0.0008, respectively). Also, IL-23R AA and AC genotypes and C alleles showed a significant association with rejection in patients receiving allograft from cadaver donor (p=0.001, p=0.002 and p=0.02). The mentioned results indicate that IL-23R AC carriers and C allele have predictive values for acute rejection. AC genotype and C allele of IL-23R is a genetic risk factor for development of acute rejection. Also, AA and AC genotype of IL-23R is a sex dependent genetic risk factor for development of acute rejection. But this subject needs to be studied in different population.

Combined analysis of cytokine gene polymorphism and the level of expression with allograft function in kidney transplant recipients.

Cytokines are important factors determining the outcome of transplantation since host ability in cytokine production may be affected by cytokine gene polymorphisms. The aim of the present study was to investigate the effect of IL-17, IL-23R and IL-21 gene polymorphisms in the outcome of kidney transplantation. A total of 250 kidney transplant recipients were included in this study. Overall 70 recipients (28%) experienced an acute rejection. IL-17 197 A/G, IL-21+1472 G/T, IL-21 5250 C/T, and IL-23R C/T gene polymorphisms were evaluated by PCR-RFLP or ARMS-PCR methods. The serum levels of IL-17 and IL-21 were also checked by ELISA. IL-17 GG carriers and G allele were significantly more frequent in patients with acute rejection as compared to patients without any sign of rejection (P=0.045 and P=0.032, respectively). In addition after gender classification, IL-23R AA carriers and A allele were significantly more frequent in male patients who experienced an acute rejection as compared to non-rejected patients (P=0.03, P=0.011, respectively). The IL-17 serum levels have also shown significant differences between rejected and non-rejected groups (24.37±32.94 for AR and 8.6±9.9 for non-AR groups, respectively; P=0.035). The mentioned results indicate that IL-17GG genotype, G allele and its serum level have predictive values for acute rejection. GG genotype and G allele of IL-17 is a genetic risk factor for development of acute rejection. Also, AA genotype and A allele of IL-23R is a sex dependent genetic risk factor for the development of acute rejection, but this subject needs to be studied in a different population.

Association of IL-17, IL-21, and IL-23R gene polymorphisms with HBV infection in kidney transplant patients.

Inflammatory cytokine gene polymorphisms may influence the hepatic and extrahepatic HBV-related disease in transplant patients. In this study, the association between IL-17, IL-23R, and IL-21 gene polymorphisms with hepatitis B virus (HBV) infection was evaluated in kidney transplant patients. In total, 220 kidney transplant patients were enrolled in this cross-sectional study between years 2007 and 2011. The genomic HBV DNA was identified using an HBV PCR detection Kit according to the manufacturer's instruction. The cytokine gene polymorphisms, including IL-17 197 A/G (rs2275913), IL-21 +1472 G/T (rs2055979), IL-21 5250 C/T (rs4833837), and IL-23R C/A (rs10889677) were evaluated by PCR-RFLP and ARMS-PCR protocols. The serum levels of IL-17 and IL-21 were analyzed in HBV infected and noninfected transplant patients by ELISA methods according to manufacturer's instructions. 70 of 220 (35%) transplant patients experienced acute rejection. HBV DNA was detected in 52 of 220 (23.64%) transplant patients. 16 of 52 (30.8%) HBV-infected kidney transplant patients experienced acute rejection. A significant higher frequency of C allele of IL-23R (rs10889677) polymorphism, a higher frequency of AG heterozygote genotype and A allele of IL-17-G197A (rs2275913) polymorphism, a higher frequency of TT homozygote genotype and T allele of IL-21-G1472T (rs2055979) polymorphism, and a higher frequency of CC homozygote genotype and C allele of IL-21-C5250T (rs4833837) polymorphism were found in HBV-infected kidney transplant patients with acute rejection. Diagnosis of the higher frequency of the IL-17, IL-21, and IL-23R cytokine genotypes and allele polymorphisms in HBV-infected kidney transplant patients who experienced acute rejection, illustrates the importance of Th17-related cytokine genetic patterns. A better evaluation of HBV infection in kidney transplant patients is needed.