Red Blood Cell Immunization Research Articles

Retracted: Effect of Tumor Red Blood Cell Immunity and Tumor Cell Cycle in Mice Bearing Solid Liver Cancer with Intelligent Cancer Zhongning Therapeutic Apparatus.

[This retracts the article DOI: 10.1155/2021/3329800.].

Effect of seasonal changes on the innate immunity of wild Pseudois nayaur: potential reason for its endangerment.

Seasonal climate change may impose stress on mammal's immune system, but this has never been connected to wildlife endangerment reasons. This study focuses on Pseudois nayaur, a rare Chinese sheep facing a severe situation of disappearing. Wild Pseudois nayaurs in Sichuan, China were observed in this research by an integrated method including habitat environment, foraging rules, and breeding activities investigation in ecology filed, accompanied with immunity research by peripheral blood, including erythrocyte, neutrophils, natural killer cells, and macrophages immunity by means of erythrocyte rosette, phagocytosis, lactate dehydrogenase release and acid alpha-naphthyl acetate esterase method, respectively. The results show that Pseudois nayaurs's innate and red blood cell immunity in autumn and winter Pseudois nayaurs and it may be the results of energy reallocation between reproduction and the immune system. In addition, the environment pressure found in Zhu Balong, Sichuan, China including food reduction, human disturbance, low temperature, and severe drought still existed, which may prevent the Pseudois nayaur from normal immunity enhancement before winter. In conclusion, the innate immunosuppression found in this study especially at their breeding season in autumn and winter may be the ignored cause of wild Pseudois nayaur's endangerment and should be considered in their protection strategy.

Red Blood Cell Immunization and Contributing Factors in 685 Thalassemia Patients.

Background: An analysis of red blood cell alloimmunization in patients with thalassemia can help to devise specific strategies to decrease the alloimmunization rate. This study explored the frequency and specificity of alloantibodies and autoantibodies against red blood cell (RBC) antigens in patients with thalassemia referring to the Iranian Blood Transfusion Organization (IBTO) Immunohematology Reference Laboratory (IRL) in Tehran. Materials and Methods: This study first examined the laboratory records of 23,113 patients suffering from different diseases referring to IBTO’s IRL for pretransfusion testing in the 2008-2015 period. ABO and Rh(D) typing and antibody screening tests were performed for all 23,113 patient records and 685 (2.97%) beta-thalassemia patients with positive pre-transfusion test results (antibody screening and/or DAT) were selected for further investigation. Results: The antibody screening test was positive in 640 out of 685 thalassemic patients (93.4%). DAT was performed for 529 patients, 226 (33%) of which showed positive results. Meanwhile, 161 out of 685 beta-thalassemia patients (23.5%) had positive auto control test results, reflecting the possible presence of allo- and/or autoantibodies. The most common antigen-specific alloantibodies were directed against K and E RBC antigens with a frequency of 25% (Anti-K) and 11.91% (Anti-E), respectively. The development of two antibodies (double antibodies) in one patient was observed in 80 individuals (11.46%). Conclusion: Age, gender, history of pregnancy, and splenectomy were not contributing factors to the antibody presence in the patient population under study. Extended red blood cell phenotyping should be considered as an essential procedure for expected multi-transfused thalassemia patients before blood transfusion. Considering the high frequency of anti-K and anti-E observed in this study, it is recommended that thalassemia patients in Iran are tested through phenotyping of RBC units for K and E antigens before transfusion.

Red Blood Cell Alloimmunization Rates and Related Factors of Patients with Thalassemia in Shiraz, Iran.

The development of antibodies against red blood cell (RBC) antigens is one of the most significant adverse effects of chronic blood transfusions. This study aimed to estimate the frequency and causes of RBC immunization in patients with major thalassemia. The findings could help determine the limitation of current practices and help future developments in the selection of suitable blood units for the transfusion support of patients with thalassemia. The alloimmunization rate was detected in 52 of 650 patients with major thalassemia (8%). The most frequent antibodies were against K (50%), D (26%), and E (15.4%). Sex, age, and splenectomy did not have any impact on the immunization rate. Immunization was lower in patients who had received only leuko-reduced blood units. It is recommended that antibody screening before the first transfusion and extended RBC matching particularly for the most frequent antigens (ABO/Rh/Kell) should be performed for patients with thalassemia.

Effect of Tumor Red Blood Cell Immunity and Tumor Cell Cycle in Mice Bearing Solid Liver Cancer with Intelligent Cancer Zhongning Therapeutic Apparatus.

People's unhealthy lifestyles, especially the number of smoking and passive smoking populations, are increasing year by year and the population is aging. With the development and progress of lung cancer cell and molecular biology, the incidence rate and mortality rate of lung cancer are increasing year by year. The existing tumor biochemotherapy has rapidly developed from preliminary research and animal research to clinical research. The smart cancer Zhongning therapeutic device can induce necrosis and apoptosis of tumor cells. The effect of treating tumors is getting more and more attention. Therefore, this article focuses on the effect of the smart cancer Zhongning therapeutic device on the tumor red blood cells and tumor cell cycle of mice with solid liver cancer. The immunological effects of the drug were discussed. Forty mice were randomly divided into high-dose group, low-dose group, 5-FU group, and model group. The effects of different treatment stages on tumor red blood cell immune function and cell cycle were recorded and evaluated, and the survival rate by multiplying the positive limit method was calculated. The model group is controlled by the exact probability method, and the Pss18.0 system is used to test the hypothesis of survival rate comparison. The experimental results showed that the tumor inhibition rate in this group was 65.8%. Compared with the 5-FU group and model group, the dose group has shown an antitumor effect and had significantly improved the tumor-bearing body's antitumor red blood cell immune function and tumor cell cycle.

Baicalin inhibits IgG production by regulating Treg/Th17 axis in a mouse model of red blood cell transfusion

This study was conducted to evaluate whether baicalin inhibits red blood cell (RBC) immunization and elucidate the underlying mechanism. We used human RBCs with adjuvant lipopolysaccharide (LPS) and transfused mice to induce antibodies as an experimental system for studying the effect of baicalin on RBC immunization. Mice were divided into a human RBC transfused positive control group administered with human RBC and LPS intravenously once or weekly for 4 weeks, control group administered dexamethasone (DEX) intraperitoneally daily for 4 weeks, and treatment group administered baicalin intraperitoneally daily for 4 weeks. Assessment of human RBC immunization was performed by measuring serum immunoglobulin G (IgG) and immunoglobulin M (IgM) against human RBC weekly. Lymphocyte changes in spleen were monitored by flow cytometry. We found that baicalin treatment significantly decreased serum IgG but not IgM production in a time and does dependent manner, with a concomitant reduction in Th17 cells and increase in CD4 regulatory T cells in the spleen. The percentage of CD4-positive cells in the spleen was not decreased in the baicalin-treated group but was decreased in the dexamethasone-treated group. In conclusion, baicalin inhibited RBC immunization, particularly IgG production by regulating the Treg/Th17 axis without damaging spleen function.

Hematology and serum biochemistry of growing New Zealand White (NZW) rabbits administered Panax ginseng extracts

This study was conducted to evaluate the hematological and serum biochemical parameters of growing New Zealand White (NZW) rabbits administered Panax ginseng extracts (PGEs). A total of 48 NZW growing male (M) and female (F) rabbits (24 each) were used and the experiment lasted for 28 days. It was carried out in a randomized complete block design (RCBD), made up of T1 (0.0 mg/ml of PGEs), T2 (200.0 mg/ml of PGEs), and T3 (400.0 mg/ml of PGEs) which was replicated thrice and sex served as the block. Packed cell volume (PCV) (34.03%), red blood cell (RBC) (5.52 × 106/μl), white blood cell (WBC) (7.60 × 103/μl), and heterophil (34.00%) counts of the growing male NZW rabbits were significantly (P < 0.05) higher in MT3 rabbits. PGEs positively affected mean corpuscular volume (MCV) of the male rabbits which recorded a significantly (P < 0.05) higher value in MT3 (400.0 mg/ml of PGEs), but negatively affected the female rabbits which recorded a significantly (P < 0.05) higher value in FT1 (0.0 mg/ml of PGEs). Total protein values were significantly (P < 0.05) different among the experimental rabbits, with the lowest value obtained from FT3 (4.58 g/dl) rabbits. Globulin values of the rabbits were significantly (P < 0.05) lower in MT3 and FT3 rabbits. Serum cholesterol of the experimental rabbits were significantly (P < 0.05) lower in PGE-treated rabbits (MT2, MT3, FT2, and FT3). Alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST) values of the growing female NZW rabbits were significantly (P < 0.05) lower in PGE-treated female rabbits. The result of this study suggests improved PCV, RBC, and cellular immunity in growing male NZW rabbits. It also suggests that PGEs have an anti-cholesterolemic effect on both male and female growing NZW rabbits.

CD4 Depletion or CD40L Blockade Results in Antigen-Specific Tolerance in a Red Blood Cell Alloimmunization Model.

Approximately 3–10% of human red blood cell (RBC) transfusion recipients form alloantibodies to non-self, non-ABO blood group antigens expressed on donor RBCs, with these alloantibodies having the potential to be clinically significant in transfusion and pregnancy settings. However, the majority of transfused individuals never form detectable alloantibodies. Expanding upon observations that children initially transfused with RBCs at a young age are less likely to form alloantibodies throughout their lives, we hypothesized that “non-responders” may not only be ignorant of antigens on RBCs but instead tolerized. We investigated this question in a reductionist murine model, in which transgenic donors express the human glycophorin A (hGPA) antigen in an RBC-specific manner. Although wild-type mice treated with poly IC and transfused with hGPA RBCs generated robust anti-hGPA IgG alloantibodies that led to rapid clearance of incompatible RBCs, those transfused in the absence of an adjuvant failed to become alloimmunized. Animals depleted of CD4+ cells or treated with CD40L blockade prior to initial hGPA RBC exposure, in the presence of poly IC, failed to generate detectable anti-hGPA IgG alloantibodies. These non-responders to a primary transfusion remained unable to generate anti-hGPA IgG alloantibodies upon secondary hGPA exposure and did not prematurely clear transfused hGPA RBCs even after their CD4 cells had returned or their CD40L blockade had resolved. This observed tolerance was antigen (hGPA) specific, as robust IgG responses to transfused RBCs expressing a third-party antigen occurred in all studied groups. Experiments completed in an RBC alloimmunization model that allowed evaluation of antigen-specific CD4+ T-cells (HOD (hen egg lysozyme, ovalbumin, and human duffyb)) demonstrated that CD40L blockade prevented the expansion of ovalbumin 323-339 specific T-cells after HOD RBC transfusion and also prevented germinal center formation. Taken together, our data suggest that recipients may indeed become tolerized to antigens expressed on RBCs, with the recipient’s immune status upon initial RBC exposure dictating future responses. Although questions surrounding mechanism(s) and sustainability of tolerance remain, these data lay the groundwork for future work investigating RBC immunity versus tolerance in reductionist models and in humans.

Identification des allo-anticorps seuls et associés : bilan de trois années au centre régional de transfusion sanguine de Rabat/Maroc et difficultés de prise en charge transfusionnelle

Red blood cell immunization can lead to delays or even an impasse in a transfusion. ObjectivesDetermine the specificities of the most common of alloantibodies and their associations to correct management of red blood cell transfused. Methods and materialsA retrospective study between 2013 and 2015 in immunohematology laboratories at the Blood Transfusion Center of Rabat in Morocco. The following data were studied: frequency, specificities of alloantibodies, blood group involved in alloimmunization and difficult of management of transfusion in case with association of alloantibodies. ResultsFive hundred of alloantibodies were identified in 425 people (372 patients/pregnant women and 53 blood donors). The alloantibodies were directed against the following antigen: RH1 (50.8 %), RH3 (11.4 %), KEL 1 (8.2 %), RH2 (7.6 %), RH4 (4.6 %), MNS1 (4 %), MNS3 (2.6 %), Jka (2.4 %) and Fya (2.2 %). Only one alloantibody was identified in 85 % of cases. In 15 %, at least, two alloantibodies were found. The most common associations were directed against: anti-(D+C) (25), anti-(E+K) (4), anti-(E+c) (3) and anti-(D+C+E) (3). The rhesus system is the most involved in alloimmunization. Frequency of specific associations of alloantibodies was identified: Fya−/Jkb− (18.23 %), Fyb−/Jkb− (11.7 %), Jka−/S− (8.70 %), Jka−/Fyb− (5.20 %), Fyb−/s− (3.40 %) and Fyb−/Jkb−/s− (0.85 %). ConclusionsRed blood cell immunization is a serious problem in transfused patients. This study proves the data of literature, the interest of using RH-Kel1 red cell units compatibles among women in age to procreate and for the transfused patients to reduce the rate of immunization. Associations of antibodies with low frequency suggest a promotion of donation.

The HLA-DRB1*15 phenotype is associated with multiple red blood cell and HLA antibody responsiveness.

Once a patient has produced a red blood cell (RBC) antibody, there is an increased risk of additional antibody formation after subsequent RBC exposure. Recently, we observed that HLA-DRB1*15 was overrepresented in 379 multiple RBC antibody responders compared to controls or 562 patients with a single RBC antibody (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.3-2.3). In this study we evaluated whether the HLA-DRB1*15 represents a responder phenotype against HLA and/or RBC antigens. HLA-DRB1*15 frequencies in single and multiple antibody responders were compared between three groups of individuals: 1) those with HLA antibodies, 2) those with RBC antibodies, and 3) those with both RBC and HLA antibodies. A total of 3959 immunized patients (female-to-male ratio, 2.3) had been HLA-DRB1 typed. Among the 3275 individuals with HLA antibodies, the frequency of the DRB1*15 phenotype differed significantly from 19.7% in patients with a panel reactivity (PRA) of not more than 20% to 26.9% in patients with PRA of more than 80% (OR, 1.5; 95% CI, 1.2-1.9). This association between DRB1*15 and multiresponsiveness was mainly due to pregnancy-induced HLA immunization. In the 257 individuals with RBC and HLA antibodies, the frequency of DRB1*15 was 4.2 times (95% CI, 1.1-16) higher in those with multiple RBC antibodies and HLA-PRA of more than 50% compared to only single RBC responders with PRA of less than 20%. The HLA-DRB1*15 phenotype is associated with broad RBC and HLA immunization.

Red blood cell alloimmunization in transfused patients with bone marrow failure syndromes.

Red blood cell (RBC) alloimmunization is a concern for patients who receive multiple or chronic transfusions. Alloimmunization prevalence in transfused patients with bone marrow failure syndrome (BMFS) is unknown. This study aimed to determine physician practice for RBC antigen matching, immunization rates, and antibody specificities in patients with BMFS. The clinical records of all patients with BMFS seen at the Children's Hospital of Philadelphia between 2001 and 2015 were reviewed. Immunization rate was determined per 100 units transfused. ABO/D, C, E, and K (CEK) RBC matching was requested for 21.8% of patients. A total of 3782 RBC units were transfused to 87 patients, of which 2551 (67.5%) were CEK matched and 1231 (32.5%) were ABO/D only matched. The majority of units transfused to patients on a chronic transfusion regimen were CEK matched (89.6% of 2728 units). No anti-C, -E, or -K antibodies formed in any patient during the 14-year study period. Two alloantibodies and two autoantibodies formed, resulting in a rate of 0.05 alloantibodies and 0.05 autoantibodies per 100 units transfused. The prevalence of alloimmunization was 2.3%. The rate and prevalence of RBC alloimmunization were low in patients with BMFS. CEK matching avoided alloimmunization to these antigens in chronically transfused patients.

Phenotypic differences of CD4(+) T cells in response to red blood cell immunization in transfused sickle cell disease patients.

Alloimmunization against red blood cells (RBCs) is the main immunological risk associated with transfusion in patients with sickle cell disease (SCD). However, about 50-70% of SCD patients never get immunized despite frequent transfusion. In murine models, CD4(+) T cells play a key role in RBC alloimmunization. We therefore explored and compared the CD4(+) T-cell phenotypes and functions between a group of SCD patients (n = 11) who never became immunized despite a high transfusion regimen and a group of SCD patients (n = 10) who had become immunized (at least against Kidd antigen b) after a low transfusion regimen. We studied markers of CD4(+) T-cell function, including TLR, that directly control lymphocyte function, and their spontaneous cytokine production. We also tested responders for the cytokine profile in response to Kidd antigen b peptides. Low TLR2/TLR3 expression and, unexpectedly, strong expression of CD40 on CD4(+) T cells were associated with the nonresponder status, whereas spontaneous expression of IL-10 by CD4(+) T cells and weak Tbet expression were associated with the responder status. A Th17 profile was predominant in responders when stimulated by Jb(k) . These findings implicate CD4(+) T cells in alloimmunization in humans and suggest that they may be exploited to differentiate responders from nonresponders.

PPARγ negatively regulates T cell activation to prevent follicular helper T cells and germinal center formation.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor that regulates lipid and glucose metabolism. Although studies of PPARγ ligands have demonstrated its regulatory functions in inflammation and adaptive immunity, its intrinsic role in T cells and autoimmunity has yet to be fully elucidated. Here we used CD4-PPARγKO mice to investigate PPARγ-deficient T cells, which were hyper-reactive to produce higher levels of cytokines and exhibited greater proliferation than wild type T cells with increased ERK and AKT phosphorylation. Diminished expression of IκBα, Sirt1, and Foxo1, which are inhibitors of NF-κB, was observed in PPARγ-deficient T cells that were prone to produce all the signature cytokines under Th1, Th2, Th17, and Th9 skewing condition. Interestingly, 1-year-old CD4-PPARγKO mice spontaneously developed moderate autoimmune phenotype by increased activated T cells, follicular helper T cells (TFH cells) and germinal center B cells with glomerular inflammation and enhanced autoantibody production. Sheep red blood cell immunization more induced TFH cells and germinal centers in CD4-PPARγKO mice and the T cells showed increased of Bcl-6 and IL-21 expression suggesting its regulatory role in germinal center reaction. Collectively, these results suggest that PPARγ has a regulatory role for TFH cells and germinal center reaction to prevent autoimmunity.

Impact on red blood cell immunity patterns in postoperative phase following total hip arthroplasty.

ObjectiveIn this study, we aimed to measure changes in red blood cell (RBC) immunity and cytokine levels after performing total hip replacement surgery.Material and methodsTwenty patients receiving total hip arthroplasty were investigated by measuring presurgical and postoperative RBC natural tumor erythrocyte rosette rate (NTERR), RBC C3b receptor rosette rate (RC3bRR), RBC membrane CD35, CD58 and CD59 expression and cytokine levels [including tumor necrosis factor α (TNF-α), interleukin 2 (IL-2), interferon γ (IFN-γ), interleukin 10 (IL-10) and prostaglandin E2 (PGE2)]. Blood samples were collected on the day before surgery and on the first day after hip arthroplasty.ResultsPostoperative NTERR and RC3bRR were significantly lower than presurgical levels (p < 0.05). The RBC membrane CD35, CD58 and CD59 expressions were significantly decreased in the postoperative phase compared to pre-operative levels. Importantly, RBC promoting lymphocyte proliferation rates were significantly reduced after surgery. In addition, postoperative TNF-α, IL-2 and IFN-γ levels in RBC and lymphocyte culture fluid were lower than those pre-operation, whereas IL-10 and PGE2 were significantly increased compared to presurgical levels (p < 0.05).ConclusionsThe modification of RBC immune function may be involved in the occurrence and development of the infection following hip arthroplasty, and this suggests a novel strategy to prevent such infection.

Red blood cell alloimmunization in transfused patients with myelodysplastic syndrome or chronic myelomonocytic leukemia

Red blood cell (RBC) alloimmunization is a major problem in chronically transfused patients because of the risk of hemolytic reactions and limited availability of compatible blood. This study was aimed at determining the characteristics of RBC alloimmunization in transfusion-dependent patients with myelodysplastic syndrome or chronic myelomonocytic leukemia (MDS/CMML). The transfusion and clinical records of all patients with MDS/CMML seen at our hospital from 1990 to 2009 were reviewed. The cumulative incidence of RBC alloimmunization was calculated by taking death as a competing risk. Incidence rates were compared by Poisson multivariate regression. A total of 272 patients were included. Median age was 74 years; 55% were men and had received a median of 33 (range, 4-421) RBC units. Forty-two (15%) patients formed 81 alloantibodies and seven autoantibodies. Three additional patients developed autoantibodies without alloantibodies. The incidence rate of RBC alloimmunization was 1 per 10.5 person-years and was independent of sex, age, and MDS diagnostic category. The cumulative incidence of alloimmunization increased with the number of RBC transfusions, reaching a plateau at 19.5% after 130 RBC units. The most common antibody specificities were Kell (26 cases), E (19), c (5), and Jk(a) (5). In 26 (62%) of the 42 alloimmunized patients, only the Rh system and Kell were involved. RBC alloimmunization occurs in 15% of MDS/CMML patients on chronic transfusion support and mostly involves the Rh system and Kell. Transfusing these patients with extended antigen-matched blood, including Kell and CcEe antigens, would presumably reduce the RBC immunization rate.

Generation of transgenic mice with antithetical KEL1 and KEL2 human blood group antigens on red blood cells

KEL1, also known as "K", is one of the most immunogenic red blood cell (RBC) antigens. KEL2, also known as "k," differs from KEL1 by a single amino acid. Anti-Kell system antibodies can lead to significant adverse clinical outcomes in humans, including hemolytic complications in alloimmunized transfusion recipients or in infants of alloimmunized mothers. To provide a platform for in-depth immunologic studies of alloimmunization and subsequent sequelae, we generated transgenic mice expressing the human KEL1 or KEL2 antigens. Vectors were created in which cDNAs encoding either KEL1 or KEL2 were regulated by an erythroid specific β-globin promoter and enhancer. Pronuclear microinjections were carried out into a C57BL6 background, and founder pups were identified by polymerase chain reaction and screened for expression by flow cytometry. RBC life span and antigen stability were assessed by dye labeling RBCs, transfusing into agammaglobulinemic (µMT) recipients, and tracking by flow cytometry. The expression of either KEL1 or KEL2 is RBC specific and first occurs on early RBC precursors. Both KEL1 and KEL2 RBCs have a normal circulatory life span and stable antigen expression. Expression of KEL1 or KEL2 does not result in altered levels of murine Kell, and resulting RBCs have normal hematologic variables. The KEL1 and KEL2 mice represent the first murine system of RBC immunity with antithetical antigens, allowing a more precise modeling of human RBC immunology in general and also a platform for development of novel therapeutics to prevent or minimize the dangers of RBC alloimmunization to the KEL1 and KEL2 antigens in particular.

HLA alloimmunization is associated with RBC antibodies in multiply transfused patients with sickle cell disease

Alloimmunization to minor red blood cell (RBC) antigens occurs commonly in sickle cell disease (SCD). Patients with alloimmunization demonstrate increased risk for new alloantibody formation with subsequent transfusion. Alloimmunization to human leukocyte antigens (HLA) can occur with RBC transfusion and may result in graft rejection during stem cell or organ transplantation. The prevalence and risk factors for HLA alloimmunization in multiply transfused pediatric SCD patients are unknown. A cross-sectional study of HLA alloimmunization in SCD patients aged 3-21 years with a history of >or=3 RBC transfusions was performed to test the hypothesis that HLA alloimmunization is associated with RBC alloimmunization. Antibodies to class I and class II HLA were measured by Flow Panel Reactive Antibody (FlowPRA). Seventy-three SCD patients (30 with RBC antibodies) were tested. HLA antibodies were detected in 25/73 (34%) patients; class I HLA antibodies occurred in 24/73 (33%) and class II HLA antibodies occurred in 3 (4%). Among patients with RBC antibodies, 16/30 (53%) had HLA antibodies, while 9/43 (21%) patients without RBC antibodies had HLA antibodies (OR 4.32 [1.6-12.1]). In a multivariate analysis, antibodies to RBC antigens were an independent predictor of HLA alloimmunization (P = 0.041). The association of RBC and HLA immunization was strongest among patients with no history of chronic transfusion therapy. This analysis is the first description of HLA alloimmunization in pediatric SCD patients who receive primarily leukoreduced RBC transfusions and demonstrates that HLA alloimmunization tendency is associated with antibodies to RBC antigens.

Haematopoietic Stem Cell Transplantation in Thalassaemic Patient with Renal Failure on Hemodialysis

Until now few patients with renal failure on hemodialysis have undergone haematopoietic stem-cell transplantation (HSCT), and none with thalassaemia. Case report. Patient of 45 years, UPN 168, with β Thalassaemia major, genetic compound β0 39 C–>T/β0 6-A, non transfusible due to red blood cell immunization (positive DAT, Hb 5–7 g/dl), under hemodialytic treatment for three years for bilateral focal nephrosclerosis. He suffered from cardiopathy (atrial thrombosis, pulmonary hypertension, atrial and ventricular dilatation), hypothyroidism, hepatopathy (HCV positive with grade II haemosiderosis). Quality of life was much harmed by the severe chronic anaemia and nephropathy. In December 2007 we performed HSCT from his HLA identical brother. Conditioning regimen included: Busulfan (Bu) IV (Busilvex Pierre Fabre Médicament) in single daily dose (3.5 mg/kg/day) for 4 days, Cyclophosphamide 40 mg/kg/day for 3 days. GvHD prophylaxis consisted of Cyclosporin 3 mg/kg/day IV (days -2 to +1), 2 mg/kg/day IV (days +2 to +42), changed to oral administration of 4 mg/kg/day from day +43. Hemodialysis was performed every other day in sterile room. Nucleated marrow cells infused: 4.4 × 108/kg. A mixed chimerism (VNTR more than 90% donor) was documented at day +19. ANC >0.5 × 109/L at day +21. PLT >20 × 109/L at day +15. Eight months after transplantation, patient is in good general condition, with stable mixed chimerism (more than 95% donor), haemoglobin above 11 g/dl, leucocytes and platelets in normal range. Substantial improvement of chronic anaemia ameliorated patient's quality of life and now patient can be considered a kidney transplant candidate. This single case report does not allow definitive conclusions to be drawn regarding HSCT suitability of patients with chronic renal failure on hemodialysis. We can observe that once-daily intravenous busulfan administration (after the hemodialysis session) has made it possible to keep therapeutic range, as has been ascertained by pharmacokinetic study of busulfan.

Red Blood Cell Allo and Autoantibody Production in Patients in the Thalassemia Clinical Research Network.

Introduction: The development of alloantibodies and/or autoantibodies, complicates red blood cell (RBC) crossmatching, shortens red cell survival, delays provision of safe transfusion and may accelerate tissue iron loading. Little is known about the incidence of alloimmunization or its inciting factors, essential data for strategies to provide optimal transfusion.Aim: To determine the frequency of RBC allo- and autoantibodies in patients with thalassemia major (TM) who are regularly transfused and whether there is an association of RBC antibodies and age at initiation of transfusion, duration of regular transfusion, splenectomy status, transfusion of leukoreduced blood or ethnicity.Methods: We utilized a cross-sectional registry of the Thalassemia Clinical Research Network (TCRN), an NHLBI-funded consortium of patients with thalassemia followed in Canada and the United States, for data on allo- and autoantibodies, splenectomy status, ethnicity and compared rates before and after 1990, when the first leukoreduction filters were introduced.Results: 502 of the 836 subjects enrolled in the TCRN registry had been regularly transfused and reported allo- and autoimmunization status. Allo- and autoantibodies were reported in 104 (21%) and 46 (9.2%) subjects, respectively. Presence of both were reported in 26 (5.2%) individuals. The rate of alloimmunization was higher among individuals who initiated transfusions prior to 1990 (27%) versus those who initiated transfusion after that date (12.5%, p<.001). The rate of autoimmunization did not differ significantly between these two cohorts (pre-1990 11.2%, post-1990 6.3%, p=.08). Mean age at time of registry entry in these cohorts was 25.8±8.4 yrs and 9.3±6.8 yrs, respectively. Duration of regular transfusion was associated with allo- (p<.001) but not autoantibodies (p=.08). Initiation of transfusions before or after 1990 and duration of regular transfusions are confounded. Consequently, the differences in alloimmunization rates may reflect the use of leukoreduction or the total years of exposure to transfusions. Splenectomy was associated with a higher rate of alloantibodies among subjects in the post-1990 but not the pre-1990 cohort. Alloantibodies were reported in 14 of 49 (29%) splenectomized subjects who started transfusion after 1990, and only 12 of 159 (7.6%) nonsplenectomized subjects (p<.001). Rates of alloimmunization did not differ among races after controlling for age. Age at initiation of regular transfusions was not associated with allo- or autoimmunization. Rates of alloimmunization differed among treatment centers, possibly related to varying procedures for phenotypic antigen matching of RBCs.Conclusions: RBC allo- and autoimmunization continue to develop in chronically transfused thalassemia patients although the availability of leukoreduced RBC may have resulted in the lower immunization rate observed in younger patients. The risk for RBC immunization that splenectomy imparts is concerning and deserves closer analysis.

Clinical and experimental studies on stomach carcinoma treated with Yangwei Kangliu granules.

To study the anti-cancer mechanism of Yangwei Kangliu (YWKL) granules from the view point of red blood cell (RBC) immunity and to investigate the relationship between RBC immunity and T lymphocyte immunity. Fifty patients with advanced gastric carcinoma were treated with a combination of YWKL granules and chemotherapy. Venous blood samples were obtained before treatment and after one course of treatment. The rosette rate of c-3b-receptor (RBC-C-3bRR), tumor and red cell (RRTR) and RBC immune complex (RBC-ICR) were measured under microscopy by counting the rosettes formed by sensitized or unsensitized yeast adherence. The T lymphocyte subset was observed by the method of APAAP. Control patients were treated with chemotherapy alone (n = 20). In addition, mouse tumor studies were performed to investigate the dynamic changes of RBC-C-3bRR, RRTR and RBC-ICR in response to treatment with YWKL granules (n = 30). Mice treated with chemotherapy alone (n = 30) or water alone (n = 30) were used as controls. The clinical therapeutic effect of combination treatment with YWKL granules and chemotherapy (i.e. the treatment group) was markedly superior to that of chemotherapy alone (i.e. the control group) (P < 0.01). In the treatment group, the rosette rates of RBC-C-3bRR and of RRTR were significantly increased (P < 0.01) after treatment, the rate of RBC-ICR was markedly decreased (P < 0.01), and the ratio of CD4 to CD8 was obviously elevated (P < 0.01). Moreover, CD8 was much lower (P < 0.01) and the ratio of CD4 to CD8 was much higher (P < 0.01) than that in the control group. The RRTR rate was positively correlated with the ratio of CD4 to CD8. In mice, on day 9 of bearing cancer, the tumor weight in the group treated with YWKL granules alone was much lower than that of the tumors in the control mice groups; in addition, the YWKL treated mice showed higher RBC immune function than the mice of the two control groups. On day 13 of bearing cancer, however, the differences in both tumor weight and RBC immune function had disappeared. The anti-cancer mechanism of YWKL granules may involve enhancement of RBC immunity and of T lymphocyte immune function, which is supported by the finding of RBC immune function being correlated with T lymphocyte immune function.