Donor Genetic Predisposition to High Interleukin-10 Production Appears Protective against Acute Graft-Versus-Host Disease.

The persistence of graft-versus-host disease (GVHD) as the principal complication of allogeneic hematopoietic cell transplantation (HCT) demonstrates that HLA matching alone is insufficient to prevent alloreactivity. We performed molecular and functional characterization of 22 candidate cytokine genes for their potential to improve matching in 315 myeloablative, 10/10 HLA-matched donor−recipient pairs. Recipients of a graft carrying the -1082GG IL10 gene promoter region variant had a three-fold lower incidence of grade II−IV acute GVHD compared to IL10-1082AA graft recipients (SHR = 0.25, p = 0.005). This was most evident in matched unrelated donor (MUD) transplants, where the greatest alloreactivity is expected. IL10-1082GG transplants did not experience an increased incidence of relapse, and, consequently, overall survival was two-fold higher in IL10-1082GG MUD transplants (HR = 0.17, p = 0.023). Longitudinal post-transplant measurements demonstrated that -1082GG is a high-IL10-producing and -expressing genotype with attenuated CD8+ T-cell reconstitution. High post-transplant donor chimerism in T- and myeloid-cells (>95%) confirmed a predominant donor, rather than recipient, genotype effect on immune function and aGVHD. To date, this is the first study to report corroborating genome-to-cellular evidence for a non-HLA donor immunogenetic variant that appears to be protective against GVHD. The incorporation of IL10 variants in donor selection criteria and clinical-management decisions has the potential to improve patient outcomes.

Genetic associations of fatigue and other symptoms following breast cancer treatment: A prospective study.

BACKGROUND: Cancer-related fatigue, mood disturbances, pain and cognitive disturbance are common after adjuvant cancer therapy, but vary considerably between individuals despite common disease features and treatment exposures. A genetic basis for this variability was explored in a prospective cohort. METHODS: Physical and psychological health of women were assessed prospectively following therapy for early stage breast cancer with self-report questionnaires. Participation in a genetic association sub-study was offered. Indices for the key symptom domains of fatigue, pain, depression, anxiety, and neurocognitive difficulties were empirically derived by principal components analysis from end-treatment questionnaires, and then applied longitudinally. Genetic associations were sought with functional single nucleotide polymorphisms (SNPs) in pro- and anti-inflammatory cytokine genes - tumour necrosis factor (TNF)-α (-308 â€‹GG), interferon (IFN)-É£ (+874 â€‹TA), interleukin (IL)-10 (1082 â€‹GA and -592 CA), IL-6 (-174 â€‹GC), IL-1ß (-511 â€‹GA). RESULTS: Questionnaire data was available for 210 participants, of whom 111 participated in the genetic sub-study. As expected, symptom domain scores generally improved over several months following treatment completion. Tumour and adjuvant treatment related factors were unassociated with either severity or duration of the individual symptom domains, but severity of symptoms at end-treatment was strongly associated with duration for each domain (all p â€‹< â€‹0.05). In multivariable analyses, risk genotypes were independently associated with: fatigue with IL-6 -174 â€‹GG/GC and IL-10 -1082 GG; depression and anxiety with IL-10 -1082 AA; neurocognitive disturbance: TNF-α -308 GG; depression IL-1ß (all p â€‹< â€‹0.05). The identified SNPs also had cumulative effects in prolonging the time to recovery from the associated symptom domain. CONCLUSIONS: Genetic factors contribute to the severity and duration of common symptom domains after cancer therapy.

Effect of Cytokine Gene Polymorphisms on Eltrombopag Reactivity in Japanese Patients with Immune Thrombocytopenia.

BACKGROUND: Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by low platelet counts resulting from antiplatelet autoantibodies. Analysis of polymorphisms in cytokine-encoding genes is important for understanding the pathophysiology of ITP and selecting appropriate treatments. We investigated associations between polymorphisms in cytokine-encoding genes and responses to therapy in Japanese patients with ITP. METHODS: The participants in this study comprised 153 patients with ITP and 70 healthy controls. We extracted data on sex, age, platelet counts, bleeding symptoms, and therapeutic responses, including those to prednisolone (PSL) and eltrombopag. Genomic DNA was isolated from peripheral blood and polymorphisms in TNF-α, IL-10, TGF-ß1, and IFN-γ genes were analyzed using the PCR-SSP method. RESULTS: Our results showed that the TGF-ß1 +869 C/C genotype might be related to ITP in Japanese patients. The IL-10 -592 C/C and A/A, -819 C/C and T/T, and -1082, -819, -592 ATA/ATA genotypes might be associated with reactivity to PSL. Furthermore, the IL-10 -592 C/A -819 C/T genotypes, IL-10 ACC/ATA genotype, and TGF-ß1 +869 T/T and T/C genotypes might be linked to the response to eltrombopag. CONCLUSION: Our results indicate that analysis of polymorphisms in cytokine-encoding genes could aid in understanding PSL and eltrombopag responsiveness in Japanese patients with ITP.

Cytokine gene polymorphisms are associated with response to blinatumomab in B-cell acute lymphoblastic leukemia.

Blinatumomab is a bispecific T cell-engaging antibody approved for treatment of relapsed/refractory (r/r) ALL, with 40%-50% complete response (CR)/CR with incomplete count recovery (CRi). Cytokine release syndrome (CRS) as a major adverse effect after blinatumomab therapy. Here, we evaluated the possible association between single-nucleotide polymorphisms (SNPs) in cytokine genes, disease response, and CRS in r/r ALL patients who received blinatumomab between 2012 and 2017 at our center (n = 66), using patients' archived DNA samples. With a median duration of 9.5 months (range: 1-37), 37 patients (56.1%) achieved CR/CRi, 54 (81.8%) experienced CRS (G1: n = 35, G2: n = 14, G3: n = 5), and 9 (13.6%) developed neurotoxicity. By multivariable analysis, after adjusting for high disease burden, one SNP on IL2 (rs2069762), odds ratio (OR) = 0.074 (95% CI: NE-0.43, P = .01) and one SNP on IL17A (rs4711998), OR = 0.28 (95% CI: 0.078-0.92, P = .034) were independently associated with CR/CRi. None of the analyzed SNPs were associated with CRS. To our knowledge, this is the first study demonstrating a possible association between treatment response to blinatumomab and SNPs. Our hypothesis-generated data suggest a potential role for IL-17 and IL-2 in blinatumomab response and justify a larger confirmatory study, which may lead to personalized blinatumomab immunotherapy for B-ALL.

Usefulness of Cytokine Gene Polymorphisms for the Therapeutic Choice in Japanese Patients with Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is characterized by systemic synovitis with bone erosion and joint cartilage degradation. Although the analysis of polymorphisms in cytokine-encoding genes is important or understanding the pathophysiology of RA and selecting appropriate treatment for it, few studies have examined such single-nucleotide polymorphisms (SNPs) specifically in Japanese patients. This study was established to investigate the associations between polymorphisms in cytokine-encoding genes, autoantibodies and therapeutic responses in Japanese RA patients. METHODS: The subjects in this study consisted of 100 RA patients and 50 healthy controls. We extracted data on sex, age, disease duration, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, and therapeutic responses, including to methotrexate (MTX) and biological disease-modifying antirheumatic drugs (DMARDs). Genomic DNA was isolated from peripheral blood, which was genotyped for IL-10, TNF-α, TGF-ß1, and IFN-γ polymorphisms. RESULTS: Regarding IL-10 (-592 C/A and -819 C/T), significant decreases in the frequencies of the IL-10 (-592) CC genotype and (-819) CC genotype were found in RA patients compared with the levels in controls. For IFN-γ (+874 T/A), a significant decrease in the frequency of the TT genotype was found in RA patients compared with that in controls. Regarding TGF-ß1 (+869 T/C), patients with positivity for anti-CCP antibody had a significantly lower frequency of the CC genotype than those with negativity for it. Furthermore, the IL-10 (-592) CC genotype and (-819) CC genotype might be related to the biological DMARD-response. CONCLUSION: Our results suggest that the analysis of polymorphisms in cytokine-encoding genes may be useful when selecting treatment for Japanese RA patients.

The effects of gene polymorphisms on susceptibility to acute GVHD and survival of allogeneic HSCT recipients: IL-10 gene polymorphisms as a more accessible target to predict prognosis.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a therapeutic modality commonly used to treat hematological and immunological disorders. Among the main complications of allo-HSCT is the acute graft-versus-host disease (a-GVHD), a condition which accounts for a high incidence of mortality. Several genes encoding inflammatory mediators may present polymorphisms, which have been implicated in the risk of developing a-GVHD. In our study, we investigated the association between genotypes of cytokine-encoding genes and the incidence and severity of a-GVHD and survival of HSCT recipients. No statistically significant association was found between IL and 6-174 G/C, INF-γ + 874 T/A, TNF-α -238 A/G, -308 A/G and IL-10-819C/T, -592 A/C polymorphisms and the presence or severity of a-GVHD. A higher risk of a-GVHD was associated with the IL-10-1082 GG genotype compared to the AA + AG genotypes of recipients and donors. The IL-10-1082 genotype can be used as a prognostic determinant to predict which HSCT recipient will be more responsive to the transplant. Thus, cytokine gene assays may be useful in the individualization of prophylactic regimens and for an appropriate selection of immunosuppressants based on the HSCT recipient's responsiveness.

Association between polymorphisms of cytokine genes and secretion of IL-12p70, IL-18, and IL-27 by dendritic cells in patients with pulmonary tuberculosis.

Proinflammatory cytokines are known to play a crucial role in the pathogenesis of tuberculosis, and gene polymorphisms in the promoter regions of cytokine genes were shown to substantially influence the secretory capacity of immune cells. In the present study, we analyzed the association between polymorphisms of the IL12B, IL18, and IL27 genes and the secretion of the proinflammatory cytokines IL-12р70, IL-18, and IL-27 by myeloid dendritic cells (mDCs) in pulmonary tuberculosis (PTB) patients. The study enrolled 334 patients with newly diagnosed infiltrative and disseminated PTB. Cultivation of mDCs was performed from non-proliferating progenitors of CD14+ blood monocytes. Cytokine secretion was evaluated by measuring cytokine concentration in the mDC culture supernatants using enzyme-linked immunosorbent essay (ELISA). To study cytokine gene polymorphisms, a polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP) were performed. Reduced secretion of IL-18 and IL-27 by mDCs in PTB patients was associated with 105A/C polymorphisms of the IL18 gene, and 2905T/G, 4730T/С, and -964A/G of the IL27 gene, respectively. Polymorphism IL12B/insertion had a bidirectional influence on the secretion of IL-12p70, being associated with decreased levels of the cytokine in infiltrative PTB and increased levels in disseminated PTB patients.

The impact of cytokine gene polymorphisms on the outcome of HLA matched sibling hematopoietic stem cell transplantation.

Graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic stem cell transplantation (HSCT); cytokines are recognized as important mediators in its pathogenesis. In this study we investigated the role of cytokine gene polymorphisms on HSCT outcome. A total of 106 patient and 98 donors were genotyped by polymerase chain reaction sequence specific primers (PCR-SSP) based assay for tumor necrosis factor-α-308 (TNFα -308), interleukin (IL)-6-174, IL-10-1082, -819, -592, Interferon-γ+874 (IFN-γ+874), and transforming growth factor-ß1 (TGF-ß1) codon10 and 25 polymorphisms. Except one in each category, all patients and donors were TNFα -308 high producers and the majority were IL-6-174 high producers (93.3% and 90.8% respectively); a pattern that would alleviate any potential biological impact. Patient's IFN-γ+874 showed significant association with the development of chronic GVHD. Patients with IFN-γ +874 high producer showed an 8 folds likelihood to develop chronic GVHD as compared to those with IFN-γ+874 low producer predicted phenotype (95% CI: 1.59-40.2, p = 0.01). Patient's TGFß1-codon 10 and 25 high/intermediate producers showed a lower incidence of acute GVHD though it did not achieve statistical significance (p = 0.065) on account of the low frequency of this genotype in our patients and donors (11.4 and 8.2% respectively). Other factors contributing to risk of GVHD included older age for both acute and chronic (p = 0.01 and 0.02 respectively) with age 24 as the best discriminating cutoff; CD34+ cell dose for chronic GVHD (p = 0.045) with a dose of 8 × 106/kg as the best discriminating cutoff; and conditioning regimen with Flu/Bu associated with the lowest incidence of acute GVHD (p = 0.003) and no impact on chronic GVHD. In conclusion the current study further indicates a potential role of some cytokine gene polymorphisms in the development of GVHD. The relative distribution of high and low producer genotypes in different ethnic groups contributes to their biological impact in different populations.

Cytokine gene polymorphism in denture stomatitis patients: A clinical study.

OBJECTIVE: This clinical study investigated the association between cytokine gene polymorphism and Candida growth in denture stomatitis (DS) patients. SUBJECTS AND METHODS: Saliva and blood samples of 160 complete denture wearers (80 healthy controls and 80 with DS) were collected for mycological and gene polymorphism testing, respectively. Salivary Candida growth and TNF-α, TGF-ß, IL-6, and IL-10 genotypes were investigated. Data were analyzed using Student's t test, Mann-Whitney U test, chi-square analysis, and continuity (yates) correction tests (p < .05). RESULTS: Candida albicans colony counts in saliva were significantly higher in the DS group and in the TNF-α GG genotype (p < .05). TGF-ß TC GG and TGF-ß CC GG haplotypes were significantly higher in DS and control groups, respectively (p < .05). C. albicans colony counts were significantly higher in control group in the TGF-ß TC GG haplotype (p < .05). Candida glabrata colony counts were significantly higher in the DS group than the control group in IL-6 GG genotype (p < .05). The difference between DS types in IL-6 genotypes was significant with lower expression level in DS type 3 than DS type 1 and also type 2 (p ≤ .01). CONCLUSION: The significant differences in some genotypes of the TNF-α, TGF-ß, and IL-6 in DS patients are promising in understanding the host defense in DS.

Association of cytokine gene polymorphisms with the complications of allogeneic haematopoietic stem cell transplantation.

The purpose of our study was to confirm the prevalence of the association between single nucleotide polymorphisms present in genes encoding cytokines and the complications occurring after haematopoietic stem cell transplantation (HSCT). 108 recipients and 81 donors were typed for TNF-α (-308), TGF-ß1 (codon 10, 25), IL-10 (-1082, -819, -592), IL-6 (-174) and INF-γ (+874). Our studies have shown a tendency toward association between the occurrence of acute form of graft versus host disease (aGVHD) and IL-6 genotype. Homozygote C/C was less likely to develop aGVHD (p=0,09). Genotype GCC/ATA in IL-10 recipient gene alone had protective effect against the occurrence of aGVHD (p=0,01). Furthermore, GCC/ATA protected the host against developing the disease in the clinically relevant grades (II-IV) (p=0,03). In addition, the recipient's T/T G/G genotype (TGF-ß1) predisposed to the development of both acute (p=0,06 - trend) and chronic (p=0,04) GVHD and also severe aGVHD (p=0,004). We also observed a statistically significant association between the genotype of recipient and the risk of infection - the protective function of the G/C IL-6 in the bloodstream infections (p=0,001). Our results suggest that IL-6, IL-10 and TGF-ß1 genotypes of recipient are the most associated with the risk of complications after HSCT.

CD38+CD8+ and CD38+CD4+ T Cells and IFN Gamma (+874) Polymorphism Are Associated with a Poor Virological Outcome.

The main objective of the work was to evaluate the use of CD38 on T lymphocytes, IFNγ (+874 A/T), and IL-10 (-1082 A/G) polymorphisms in HIV-infected patients under antiretroviral (ARV) therapy. Sixty-one patients were selected at the outpatient clinic for HIV infection at the Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil. The patients were classified into two groups, according to viral load after one year of ARV therapy. In the aviremic group (group I), a reduction of 35.5% of CD38+CD4+ T cells was observed (p = 0.02) and 49.3% of CD38+CD8+ T cells (p = 0.001). In the viremic group (group II), a reduction of 37.2% of CD38+CD4+ T cells (p = 0.067), and 21.4% of CD38+CD8+ T cells (p = 0.60) occurred. No association was found between IL-10 (-1082) polymorphism and the type of response to ARV therapy. Regarding the gene polymorphism on IFNγ (+874 T/A), 73.34% of group I and 33.3% of group II presented the AA genotype. The relative risk of the individuals carrying AA genotype or the A allele and not being able to suppress the viral load level after one year of ARV therapy was 3.44 (1.25-9.45; p = 0.014) or 2.35 (1.05-5.26; p = 0.027), respectively. Our data suggested that an augmented frequency of activated CD38+CD8+ T cells as well as the presence of the A allele of IFNγ polymorphism could contribute to a reduced virological suppression in patients under antiretroviral therapy.

A study of TNF-α, TGF-ß, IL-10, IL-6, and IFN-γ gene polymorphisms in patients with depression.

In the last decade it was found that functional polymorphisms in the promoter and/or coding regions of regulatory genes are likely to pre-determine the phenotype manifestation of a certain cytokine profile, and thus could be used as disease-associated markers. Having in mind the hypothesis of impaired cytokine regulation in depressive disorder, as well as the diverse population-dependent results for cytokine polymorphisms, we investigated the relation between the cytokine gene polymorphisms of key pro- and anti-inflammatory cytokines (TNF-α, TGF-ß, IL-10, IL-6, IFN-γ) and susceptibility as well as clinical course of depression in Bulgarians. The study included 80 patients with depression (50 women and 30 men) and 50 healthy controls. Simultaneous analysis of eight polymorphic positions in the cytokine genes listed was performed by PCR-SSP method. The results revealed significant predominance of TGF-ß TT (+869) genotype (previously described as predicting low expression activity of TGF-ß) in patients (41.3%) compared to healthy subjects (21.2%) (p=0.05, OR=2.62). Furthermore T/T G/C combined genotype (+869, +915) in the same gene was negatively associated with disease recurrence. Additionally we found that certain IL-10 genotypes associated with low gene expression seemed to shape moderate disease manifestation. In conclusion our results mainly demonstrated prevalence of a low-expression TGF-ß1 profile in the patients. Thus, although in an indirect way, we supported the hypothesis of impaired immunosuppression by means of Th3 regulation in major depressive disorders.

Understanding the role of cytokines in the pathogenesis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease of unknown etiology. It is characterized by the presence of rheumatoid factor and anti-citrullinated peptide antibodies. Initial phase of RA involves the activation of both T and B cells. Cytokines have a crucial role in the pathophysiology of RA as pro-inflammatory cytokines such as TNFα, IL-1, IL-17 stimulates inflammation and degradation of bone and cartilage. There occurs an imbalance between the pro- and anti-inflammatory cytokine activities which leads to multisystem immune complications. There occurs a decline in the number of Treg cells which may also play an important role in pathophysiology of the disease. In RA patients, serum or plasma level of cytokines may indicate the severity of disease. Cytokine gene polymorphism could be used as markers of susceptibility and severity of RA. Anti-cytokine agents seem to emerge as potent drug molecules to treat RA. Many clinical trials are ongoing and several positive results have been obtained. There is a need to develop potential anti-cytokine agents that target numerous pathways involved in the pathogenesis of RA. This review article describes the effector functions of pro- and anti-inflammatory cytokines and the role of cytokine gene polymorphism in the pathogenesis of RA. Anti-cytokine agents that are currently available and those that are still in clinical trials have also been summarized.

The association of cytokine genes polymorphisms and susceptibility to aplastic anemia in Egyptian patients.

BACKGROUND AND OBJECTIVE: Aplastic anemia (AA) remains a rare disease, with very interesting pathophysiology that is being investigated for years now. The present study aimed to determine the association between cytokine gene polymorphisms (TGF-ß1 -509 C/T, TNF-α -308 G/A, IFN-γ +874 A/T) and susceptibility to AA in Egyptian patients. METHODS: The study included 80 participants subjected to determination of gene polymorphisms on genomic DNA using polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS: It was found that IFN-γ +874 A/T gene polymorphism is associated with three-fold increased risk of development of AA (odds ratio (OR) 3.116, P = 0.019), while TNF-α -308 G/A gene polymorphism is associated with decreased risk (OR 0.318, P = 0.026). TGF-ß1 -509 C/T gene polymorphism showed comparable risk between patients and controls (P = 0.263). CONCLUSION: IFN-γ +874 A/T gene polymorphism is associated with the etiology of AA in Egyptian patients.

Influence of genetic polymorphisms of cytokine genes in the outcome of HLA-matched allogeneic stem cell transplantation in a South East Asian population.

Non-HLA gene polymorphisms have been shown to be associated with the risk of graft-versus-host disease (GVHD) and outcome of allogeneic haematopoietic stem cell transplantation (AHSCT). This study aims to investigate the role of IL6, TNFα, IL10, IL2 and IL12 gene polymorphisms in the outcome of AHSCT in a South East Asian population. A total of 67 patients and 59 donors who underwent HLA-identical matched sibling AHSCT were available for analysis. There was no significant association between the different cytokine genotypes of patients with the incidence and severity of acute GVHD. Patients with IL2 166∗T allele and patients who received donor stem cells who had IL2 166∗G allele appeared to have reduced incidence of cGVHD. Patients who received donor stem cells with IL12 1188∗C allele are found to be associated with better disease free survival. These results suggest a possible role of IL2 and IL12 gene polymorphisms in the outcome of AHSCT in a South East Asian population.

Severe preeclampsia: association of genes polymorphisms and maternal cytokines production in Brazilian population.

INTRODUCTION: Preeclampsia (PE) is a multi-system disorder of pregnancy characterized by hypertension and proteinuria. Healthy pregnancy is associated with a controlled inflammatory process, which is exacerbated in PE in response to excessive placental stimuli. Gene expression levels can affect inflammation and immune regulation. It is known that differences in cytokine allele frequencies amongst populations may contribute to difference in the incidence of several diseases. OBJECTIVE: The aim of this study was to investigate the frequency of TNF-α, IL-6, IFN-γ and IL-10 genes polymorphisms and their relationship with the cytokines plasma levels in PE. METHODS: A total of 281 women were included in this study; 116 with severe PE, 107 normotensive pregnant and 58 non-pregnant women. Cytokine genotyping was carried out by the polymerase chain reaction. The analyzed polymorphisms were: TNF-α (-308 G→A), IL-10 (-1082 G→A), IL-6 (-174 G→C), and IFN-γ (+874 A→T). Cytokine plasma levels were measured by Cytometric Bead Array method. RESULTS: A higher frequency of the IFN-γ (+874) T/T genotype in severe PE comparing to normotensive pregnant women was found (P<0.001). TNF-α, IL-6 and IFN-γ plasma levels were higher in PE women compared to non-pregnant women (P<0.001; P<0.001; P=0.004). IL-6 and IFN-γ levels were also higher in PE women compared to normotensive pregnant (P<0.001; P=0.010). IL-10 levels were higher in normotensive pregnant women compared to PE (P<0.001). IFN-γ and IL-6 genes polymorphisms influenced the genic expression in PE and normotensive pregnant women, respectively. CONCLUSIONS: These results suggest that IFN-γ seems to play a role in PE occurrence.

Cytokine gene polymorphisms support diagnostic monitoring of Romanian multiple myeloma patients.

INTRODUCTION: Cytokines and their receptor genes are very polymorphic. SNPs in the promotor region of the gene may influence the rate of cytokine secretion and may affect the biological activity of the encoded cytokine. A number of cytokines and cytokine receptors have been directly linked to the development of human cancers. The aim of our study was to determine the cytokine gene polymorphism in Romanian multiple myeloma patients. MATERIAL AND METHODS: Cytokine genotyping was performed in 80 patients and 100 healthy blood donors using molecular biology methods (SSP-Invitrogen, USA). RESULTS: Analyzing each polymorphic site, there was an increased frequency of the following genotypes in patients compared to control group: Interleukin-1beta (IL-1ß) pos.+3962 TT, IL-12 pos.-1188 CC, gamma-Interferon (γ-IFN) pos.+874 AA, Transforming Growth Factor- beta1 (TGF- ß1) codon10 TT, IL-2 pos.-330 TG and pos.+166 TT, Interleukin-4Receptor alpha (IL-4Rα) pos.-33 TC, IL-10 pos.-1082 GG and pos.-592 CC, IL-6 pos.-174 GG. It should be noted that almost one third of multiple myeloma patients had IL-6 pos.-174 GG genotype and 62% IL-10 GCC haplotype. These identified haplotypes are high interleukins producer, and this fact was confirmed by serum IL-6 and IL-10 levels performed by ELISA and enhanced chemiluminiscence methods. CONCLUSION: These markers could be successfully used, together with other specific clinical and biological parameters, as reliable individualized prognostic factors in multiple myeloma patients.

Association of cytokine genetic polymorphism with hepatites B infection evolution in adult patients

The infection by the hepatitis B virus (HBV) has different forms of evolution, ranging from self-limited infection to chronic hepatic disease. The objective of this study was to evaluate the influence of cytokine genetic polymorphisms in the disease evolution. The patients were divided into two groups, one with chronic HBV (n = 30), and the other with self-limited infection (n = 41). The genotyping for TNF (-308), TGFB1 (+869, +915), IL-10 (1082, -819, and -592), IL-6 (-174), and IFNG (+874) was accomplished by the PCR-SSP (polymerase chain reaction with sequence specific primers technique using the One Lambda kit. Although no statistically significant differences were found between the groups, the combination of TNF -308GG and IFNG +874TA was found in a lower frequency in chronic patients than in individuals with self-limited infection (26.7 versus 46.3 percent; P = 0.079; OR = 0.40; IC95 percent = 0.14-1.11). In chronic patients with histological alterations it was not observed the genotype TGFB1+869 C/C, against 24.4 percent in the self limited infection group (100 versus 75.6 percent; P = 0.096; OR = 7.67; IC95 percent = 0.42-141.63). Further studies in other populations, and evaluation of a greater number of individuals could contribute for a better understanding of the cytokine genetic polymorphism influence in HBV infection evolution.