MARCH-I: A negative regulator of dendritic cell maturation.

The expression of costimulatory molecules such as MHC-II, CD86 and CD83 on dendritic cells (DCs) are strongly regulated during cellular activation. Ubiquitination of some of these markers by the E3 ubiquitin ligase MARCH-I affects the maturation state of DCs and subsequently modulates immune responses. The effects of MARCH-I gene overexpression on the functional activity of human DCs is not well understood. Here, we investigate how MARCH-I, regulates maturation of DCs. We now provide evidence that MARCH-I transduced DCs secrete high levels of IL10 despite low secretion of IL 6 and IL 12 in response to LPS stimulation. They are weak stimulators of T lymphocyte cells but skewed T cell polarization toward T regulatory subset. These results exhibit that reduced expression of surface costimulatory molecules suppresses DC activation. It can be concluded that overexpression of MARCH-I gene in DCs leads to the production of tolerogenic DC.

Comparison of MicroRNAs Mediated in Reactivation of the γ-Globin in ß-Thalassemia Patients, Responders and Non-Responders to Hydroxyurea.

Drug induction of Hb F seems to be an ideal therapy for patients with hemoglobin (Hb) disorders, and many efforts have been made to reveal the mechanism behind it. Thus, we examined in vivo expression of some microRNAs (miRNAs) that are thought to be involved in this process. Among ß-thalassemia (ß-thal) patients who were undergoing hydroxyurea (HU) therapy in the past 3 months and five healthy individuals, five responders and five non-responders, were also included in the study. Erythroid progenitors were isolated by magnetic activated cell sorting (MACS) and miRNA expression analyzed using reverse transcription-polymerase chain reaction (RT-PCR). We showed that γ-globin, miR-210 and miR-486-3p had higher levels in the responders than the non-responders group. Moreover, miR-150 and miR-320 had higher levels in the healthy group than both non-responders and responders groups, but the expression of miR-96 did not show any significant difference between the study groups. To the best of our knowledge, this is the first study proposing that 'induction of cellular hypoxic condition by Hb F inducing agents' could be the milestone of possible mechanisms that explain why responders are able to reactivate γ-globin genes and subsequently, more production of Hb F, in response to these agents in comparison to non-responders. However, further investigations need to be performed to verify this hypothesis.

The impact of pre-donation viral markers screening of new blood donors on blood safety.

BACKGROUND: The risk of transfusion-transmissible infections (TTIs) remains a concern in transfusion medicine. Since the rate of infection among first-time blood donors is higher than repeated donors, strategies to enhance blood safety can focus on new donors. The aim of the study was to investigate the effect of pre-donation viral screening of new donors on blood safety. METHODS AND MATERIALS: The pre-donation screening of new donors was implemented in the Kurdistan blood center. In this program, new donors who met the blood donation criteria were informed about the program and only a blood sample was donated for HBs Ag, HCV Ab, and HIV Ab testing. New donors with negative results were invited to donate blood after 12 weeks. A unit of blood was collected from eligible returned donors. Laboratory tests were performed again using the same methods. Finally, the prevalence of confirmed positive TTI results among donated blood in Kurdistan blood center was compared before and after the establishment of program. RESULTS: During the study, 4,434 new donors were screened for viral markers. A total of 41 new donors (0.92%, 95% CI, 0.007-0.13) had repeatedly reactive results and infection was confirmed in blood sample of 24 donors (0.54%, 95% CI, 0.003-0.008). Overall, 56% of new donors returned for blood donation. Prevalence of confirmed TTIs markers in collected blood units was 0.27% and 0 before and after implementing program, respectively. CONCLUSIONS: This study indicated that Pre-donation screening can reduce the risk of TTI transmission by identifying infected donors at the pre-donation phase.

The status of blood safety in ECO member states.

BACKGROUND: Access to the information concerning blood safety is essential for managing problems and overcoming the challenges that are faced in any given region. Information on the availability and safety of blood in countries of the Economic Cooperation Organisation (ECO) is largely lacking. To address this problem, the Iranian Blood Transfusion Organisation, in collaboration with other ECO member states, initiated a research project in 2009 to collect, analyse and compare statistics on blood safety in the region. MATERIALS AND METHODS: A modified and summarised version of the Global Database on Blood Safety (GDBS) questionnaire was used to collect data. The questionnaire was sent to all ten countries in the ECO region. The heads of the national transfusion services or focal points were requested to complete the form. Related literature and websites were also reviewed. RESULTS: Only three countries (Afghanistan, Iran and Turkey) completed the questionnaire, while other countries provided their available data on some parts of the questionnaire. The number of donations per year varied from 5 to 27/1,000 population. The rate of donors positive for human immunodeficiency virus ranged from 0.003% to 0.2%. The rate of donors positive for hepatitis C virus antibody varied from 0.05% to 3.9% while that of hepatitis B virus surface antigen ranged from 0.15% to 3.91% respectively. DISCUSSION: There is very clear diversity in blood transfusion services among ECO member states. Most countries in the region do not have a data-recording system. It is generally estimated that the need for blood is much higher than the supply in this region. Deficiencies in donor screening and a high prevalence of transfusion-transmitted infections are other important challenges.

Association of cytokine/costimulatory molecule polymorphism and allograft rejection: a comparative review.

One reason for genetic variations among human individuals is SNP which may confer diverse disease susceptibility or resistance in a population. Genetic variations in a key immunoregulatory agent can manifest various immunological responses, such as graft rejection. In fact, the outcome of organ transplantation can be impacted by several genetic causes including polymorphisms in genes encoding cytokines and costimulatory molecules in the donor or recipient. Thus, it can be helpful to contemplate the SNPs relating to these immunological determinants in order to achieve an improved transplantation therapy.

Non-association of IL-12 +1188 and IFN-γ +874 polymorphisms with cytokines serum level in occult HBV infected patients.

BACKGROUND/AIM: Occult hepatitis B infection (OBI) is identified as a form of hepatitis in which despite the absence of detectable HBsAg, HBV-DNA is observed in peripheral blood of patients. The main aim of this study has been to investigate the association between polymorphisms in +874 of IFN-γ and +1188 of IL-12 with their serum level in patients suffering from OBI. MATERIALS AND METHODS: In this experimental study, plasma samples of 3700 blood donors were tested for the presence of hepatitis B surface antigen (HBsAg) and anti-HBc by ELISA. The HBsAg-/anti-HBc+ samples were selected and screened for HBV-DNA by PCR. HBV-DNA positive samples were assigned as OBI cases and ARMS-PCR techniques were performed to examine the two known polymorphisms within IL-12 and IFN-γ. In addition, the serum levels of IL-12 and IFN-γ were also determined by ELISA. RESULTS: Results of this study demonstrated that, 352 (9.5%) out of 3700 blood samples were HBsAg-/anti-HBc+ and HBV-DNA was detected in 57/352 (16.1%) of HBsAg-/anti-HBc+ samples. Our results showed that groups showed significant difference in CC allele of +1188 region of IL-12 and no difference was observed in the other evaluated genes. Our results also showed that the alleles of +1188 region of IL-12 and alleles of +874 of IFN-γ were also not associated with serum level of cytokines. CONCLUSION: According to the results of this study, it may be concluded that the polymorphisms in +1188 region of IL-12 and +874 region of IFN-γ would not affect the expression of both cytokines at serum level in OBI patients.