Cellular Immune Dysfunction Research Articles

Study of the prevalence of azoospermia in patients with Hodgkin′s lymphoma prior to treatment

Background:Infertility is one of the main problems of patients with Hodgkin's lymphoma, as this causes specific effects in the social, family, and emotional life of patients. Hodgkin's lymphoma is a neoplastic disorder that comprises of 0.6% of all cancers and often occurs in middle-aged people, with a mean age of 26 years. It originates from neoplastic changes in the lymphoid cells, which lead to different complications in the body organs. One important complication of Hodgkin's lymphoma is humoral and cellular immune system dysfunction that can cause numerous and dangerous problems for patients. Another complication of Hodgkin's lymphoma is sterility, more specifically hypogonadism and azoospermia. Sterility may appear after treatment. Considering that most patients with Hodgkin's lymphoma have a good survival, diagnosing and treating this complication and preventing its incidence contributes to improving the quality of social life and emotional status of these patients.Materials and Methods:In this study, 238 patients whose Hodgkin's lymphoma was approved by Pathology were included in the study, before receiving any medical intervention, and they were examined for sterility (sperm status). Sterility of the male patients was confirmed using a spermogram test. The serum levels of the luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) were checked.Results:Among the studied patients, 24 patients (10.08%) suffered from azoospermia, which was evident in its progressive stages.Conclusion:In such cases, treatment of Hodgkin's lymphoma and improvement of the immune system could overcome azoospermia and sterility.

Associated Immunological Disorders and Cellular Immune Dysfunction in Thymoma: A Study of 87 Cases from Thailand

Several immune disorders are often associated with thymoma. The aim of this study was to analyze the correlation between clinicopathological features of Thai patients with thymoma and concomitant immune-mediated diseases. Medical records of 87 patients diagnosed with thymoma during a 10-year period were retrospectively reviewed. Peripheral blood T cell subsets along with cytokine responses in 15 thymoma patients and 15 healthy controls were comparatively analyzed. The results demonstrated that thymoma type AB and B2 were the most common types among patients diagnosed with thymoma. The most common presentation was incidentaloma, followed by local chest symptoms and autoimmune diseases. The prevalence of autoimmune diseases, immunodeficiency states, and secondary neoplasms was 34.5, 10.3, and 10.3%, respectively. Autoimmune diseases were most frequently found in thymoma type B2 and sometimes associated with clinical immunodeficiency, although classic Good's syndrome was rare. Patients with thymoma had significantly lower percentage CD4(+ve) T cells and interferon γ response, but higher percentage regulatory T cells than those in healthy controls. This study indicated that the aberrant immunologic disorders comprising autoimmune diseases, immunodeficiency states, and secondary neoplasms were found in almost 40% of Thai patients with thymoma and possibly related to defectiva cytokine responses and altered T cell subsets.

Abnormality of regulatory T-cells in remission and non-remission idiopathic thrombocytopaenic purpura patients

Primer immunologic defect in patients with idiopathic thrombocytopaenic purpura (ITP) result from autoreactive B-lymphocytes secreting antiplatelet antibodies. Dysfunctional cellular immunity has also great importance in ITP pathogenesis. CD4+CD25+ regulatory T-cells have immunoregulatory features and it is able to inhibit CD4+CD25− and CD8+ responses. ITP is also an autoimmune disease; the CD4+CD25+ T-cell levels of the patients decrease during the active state. According to our findings, immunosuppressive treatments increase the CD4+CD25+ Treg cell levels in the non-remission ITP patients. However, this level is not enough to overcome the resistance. CD4+CD25−Foxp3+ and CD4+Foxp3+ Treg cells are responsible for the pathogenesis of the non-remission ITP patients and other factors exist, which are responsible for the resistance of ITP treatment.

Visceral Varicella in a Patient With Chronic Lymphocytic Leukemia Treated With Fludarabine: A Case Report

Introduction Opportunistic infections are a common cause of morbidity and mortality in patients with CLL. Dermatomal reactivation of the varicella zoster virus is seen in nearly half of patients undergoing treatment with fludarabine. Visceral involvement of varicella, however, is rare and likely marks severely dysfunctional cellular immunity. Visceral varicella has been reported in patients receiving high dose chemotherapy, cyclophosphamide, and rituximab. Here we report the first case of visceral varicella in a patient with CLL during fludarabine therapy. Immunosuppression associated with malignancy and its treatment can lead to infectious complications. Prompt diagnosis in the immunosuppressed patient requires recognition that common illnesses can have uncommon presentations. Opportunistic infections are often seen in patients receiving high dose chemotherapy but are less fre-

The characteristics of immunocompetent cells in peripheral blood on prophase of severe hepatitis B

To analyze the characteristics of immunocompetent cells in peripheral blood on prophase of severe hepatitis B (PSHB). 48 cases of PSHB patients, 35 cases of chronic hepatitis B (CHB) patients and 20 cases of healthy volunteers were enrolled for detection of CD3+, CD3+/ CD4+, CD3+/CD8+ and CD4+/CD25+/CD45+ lymphocyte subsets in peripheral blood by flow cytometry. The absolute numbers of each lymphocyte subset were calculated and analyzed statistically. Results Compared with CHB group and healthy control group, The absolute numbers of circulating CD3+, CD8+ T cells and CD4+ CD25+ regulatory T cells (Tregs) were significantly lower in PSHB group( P < 0. 01 or P < 0.05). There was no significant difference on the absolute numbers of circulating CD4+ T cells between PSHB group and CHB group (P > 9.05), while the percentage of lymphocyte subsets CD4+ in PSHB group was significantly higher than that in CHB group (P < 0.05). In addition, CD4+/CD8+ ratio in PSHB were significantly higher than those in the CHB group and healthy control group (P < 0.01 or P < 0.05). PSHB has a certain degree of cellular immune dysfunction, which characterized by CD4+ T cells dominated and the decline of absolute numbers of CD8+ T cells and CD4+ CD25+ Tregs.

Systemic Lupus Erythematosus: Genomics, Mechanisms, and Therapies

Systemic Lupus Erythematosus: Genomics, Mechanisms, and Therapies

HIV/AIDS—Maintaining Momentum, Accelerating Action

THE GRAVITY OF THE SHORT REPORT DESCRIBING 5 young men with a possible “cellular-immune dysfunction” published 30 years ago could not have been fully appreciated at the time. However, the fear and frustration associated with subsequent spread of the disease later known as AIDS have been etched into the memory of those clinicians who stood at the forefront of the epidemic. Three decades after the MMWR report, effective antiretroviral drugs are at the clinician’s disposal and prevention strategies are being implemented with vigor. In 2011, the Joint United Nations Programme on HIV/AIDS reported slowing of the rate of new cases of human immunodeficiency virus (HIV) infection globally. This good news is tempered by the reality that an estimated 34 million persons have HIV infection worldwide. For those individuals fortunate enough to receive treatment, several vexing issues remain, including drug resistance, drug toxicity, and coinfections. Although progress in combating HIV/AIDS has been extraordinary, additional approaches are needed. As in prior years, in July 2012 JAMA will publish a theme issue highlighting HIV/AIDS research, scheduled to coincide with the 19th International AIDS Conference in Washington, DC. The issue will have an expanded focus, to include HIV/tuberculosis coinfection and HIV/ hepatitis C coinfection. JAMA invites authors to submit evidence-based manuscripts on HIV-related prevention and treatment for consideration for publication. Original research, particularly randomized controlled trials of HIV therapy, will receive the highest priority. However, systematic reviews and scholarly commentaries are also welcome. Topics on HIV basic science and the clinical application thereof, behavioral and preventive intervention strategies, epidemiology, and studies relevant to an international context are also of interest. Submitted manuscripts will undergo editorial review and, if appropriate, will then be evaluated through the peer review process. Authors should refer to the JAMA Instructions for Authors concerning the preparation and submission of papers, and are encouraged to contact us with any questions. Manuscripts received by February 27, 2012, will have a higher chance of being considered for the 2012 HIV/AIDS issue. Since the initial report in 1981, knowledge has been painstakingly acquired that now points to a hopeful future with a possible end to the pandemic. With that goal in mind, we look forward to receiving your manuscripts for consideration for the 2012 HIV/AIDS theme issue.

Progressive Multifocal Leukoencephalopathy in a Patient without Immunodeficiency

# {#article-title-2} The case report by Tan et al.1 of a 62-year-old man with progressive multifocal leukoencephalopathy (PML) without immunodeficiency was interesting given our experience with AIDS-related PML and current literature.2 The authors assume that their patient's disease was due to reactivation of latent JC virus infection caused by a transient dysfunction of cellular immunity triggered by another subclinical viral infection such as parvovirus B19. …

Clinical Monoclonal B Cell Lymphocytosis Is a Strong Favorable Prognosticator Independent From Biological and Clinical Parameters,

Abstract 3887Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic monoclonal expansion of <5.0 × 109/L circulating CLL (chronic lymphocytic leukemia)-phenotype B-cells. CLL-like MBL, observed in the clinical setting and defined as clinical MBL (cMBL), demonstrated a substantial risk of leukemic progression to symptomatic disease requiring treatment that can be predicted by biological prognosticators (Rawstron, 2008; Rossi, 2009). Based on this background, the aims of our study were: (i) to define clinical features at diagnosis and a biological profile of cMBL and Rai 0 subsets; (ii) to determine treatment free survival (TFS) within cMBL in comparison with Rai 0 CLL; (iii) to identify clinical and biological variables at diagnosis that predict the risk of evolution from MBL to CLL requiring treatment; and finally (iiii) to validate cMBL as an independent prognostic factor. For this purpose, we investigated 516 patients, median age 66 years (range 33–89), 288 males and 228 females. According to the IWCLL 2008 guidelines, 109 cases were diagnosed as cMBL and 407 cases as CLL (Rai 0: 106; I-II: 290; III-IV: 11). Cases presented for initial evaluation at our Institution between June 1989 and June 2009. The database was updated for the analysis in January 2011. The median follow up was 6.5 years (range 1–20). Among cMBL, median absolute lymphocyte count was 7.3 × 109/L (range 3.2–12.6 × 109/L) and median CLL-phenotype lymphocyte count was 3.5 × 109/L (range 0.6–4.9 × 109/L). cMBL were characterized by both lower beta2-microglobulin (beta2-M) and soluble CD23 (sCD23) levels (P=0.008 and P=0.0005) than Rai 0 CLL. Moreover cMBL showed a more favorable genetic profile compared to Rai 0 CLL: more specifically, cMBL showed both a significant higher prevalence of normal karyotype (45/72 [63%]] vs 30/75 [40%]) and a lower incidence of del11q/del17p (5/72[7%] vs 11/75[15%] (P=0.020). IgVH mutational status as well as ZAP-70 and CD38 percentages did not differ significantly between these two groups. Lymphocyte doubling time was <12 months in 6/109 (5.5%) cMBL cases compared to 19/106 (18%) Rai 0 CLL (P=0.005). With regard to clinical outcome, only 12/109 (11%) cMBL patients required treatment, while 35/106 (33%) Rai 0 CLL underwent chemotherapy (P=0.00012). Noteworthy, also the time to treatment was significantly longer in cMBL patients (71.5 months vs 53.5 months, P=0.03). The slower disease kinetics was consistent with a longer TFS in cMBL compared to Rai 0 CLL (72% vs 42% at 14 years, P=0.00001, Figure). Interestingly, while, within Rai 0 CLL subset, biological prognosticators such as IgVH status (P=0.01), ZAP-70 (P=0.0002) and cytogenetics (P=0.02) as well as markers of tumor burden such as beta2-M (P=0.002) and sCD23 (P=0.0006) were confirmed to predict TFS, within cMBL none of these factors was able to predict progression free survival (PFS) and/or TFS, although some biological prognosticators (ZAP-70 and IgVH) were represented in similar percentages between these two groups. It might be hypothesized that some other factors related to the immune function (e.g., phenotype and function of T-lymphocyte subsets [G.D.P., unpublished observation]) could be able to explain the different time to progression of the cMBL patients. Finally, multivariate analysis, combining cMBL and Rai 0 CLL, documented that having a diagnosis of cMBL is an independent protective factor against the risk of treatment (P=0.011), together with a normal karyotype (P=0.020) and a lower ZAP-70 expression (P=0.0001). In conclusion, cMBL represents a biological and clinical distinct entity from Rai 0 CLL with a more favorable outcome, displaying some degree of heterogeneity in the risk of treatment requirement, probably due to both humoral and cellular immune dysfunctions. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Deranged Bioenergetics and Defective Redox Capacity in T Lymphocytes and Neutrophils Are Related to Cellular Dysfunction and Increased Oxidative Stress in Patients with Active Systemic Lupus Erythematosus

Urinary excretion of N-benzoyl-glycyl-Nε-(hexanonyl)lysine, a biomarker of oxidative stress, was higher in 26 patients with active systemic lupus erythematosus (SLE) than in 11 non-SLE patients with connective tissue diseases and in 14 healthy volunteers. We hypothesized that increased oxidative stress in active SLE might be attributable to deranged bioenergetics, defective reduction-oxidation (redox) capacity, or other factors. We demonstrated that, compared to normal cells, T lymphocytes (T) and polymorphonuclear neutrophils (PMN) of active SLE showed defective expression of facilitative glucose transporters GLUT-3 and GLUT-6, which led to increased intracellular basal lactate and decreased ATP production. In addition, the redox capacity, including intracellular GSH levels and the enzyme activity of glutathione peroxidase (GSH-Px) and γ-glutamyl-transpeptidase (GGT), was decreased in SLE-T. Compared to normal cells, SLE-PMN showed decreased intracellular GSH levels, and GGT enzyme activity was found in SLE-PMN and enhanced expression of CD53, a coprecipitating molecule for GGT. We conclude that deranged cellular bioenergetics and defective redox capacity in T and PMN are responsible for cellular immune dysfunction and are related to increased oxidative stress in active SLE patients.

Type 2 polarized immune response holds a major position in Epstein–Barr virus‐related idiopathic thrombocytopenic purpura (EBV‐ITP)

Dysfunctional cellular immunity is considered to be essential to the pathophysiology of Epstein-Barr virus-related idiopathic thrombocytopenic purpura (EBV-ITP). Cytokines in peripheral blood and the gene expression of transcription factors in T lymphocytes of patients with were investigated to correlate the polarization of T helper cell type 1 (Th1)/T helper cell type 2 (Th2) with the degree of thrombocytopenia. The expression of type 1 (T-bet) and type 2 (GATA-3) in T lymphocytes was detected by semiquantitative reverse-transcription-polymerase chain reaction, and plasma cytokine levels were measured by enzyme-linked immunoassay in 35 patients and 30 control subjects. Th1/Th2 [(interleukin-2 + γ-interferon)/(interleukin-10 + interleukin-13)] cytokine ratios and transcription factor (T-bet/GATA-3) mRNA ratios were significantly decreased in patients with EBV-ITP, and the Th1/Th2 ratio was directly correlated with platelet counts. Our findings clearly show that type 2 polarization of the autoimmune response accounts for the expression of cytokines and transcription factors in EBV-ITP.

Relationship ofcell-mediated immunity with treatment in recurrent genital herpes

：Objective To observe thetherapy efficacy in patients with recurrent genital herpes (RGH)via the detection of thechange in peripheral blood T-lymphocyte subpopulation,and to explore the relatedmechanisms of cell-mediated immunity.Methods 52 patients received a 4-course thempy withoral famciclovir of 250mg,thrice daily for 5 days and an injection of thymopentin of 1 mgonce daily for 15days.T-lymphocyte subpopulation(CD3+.CD4+.CD8+,and CD4+/CD8+)was detectedby flow cytometry before and after treament.The results were then compared those from thehealthy controls.Results As compared with those the control group,CD3+.CD4+.andCD46/CD8+were decreased and CD8+was increased in the treatment group,with a statisticaldifference between the two groups(P＜0.01 ). After a 2-monththerapy with antiviral drugs and immunomodulators,CD3+.CD4+ and CD4+/CD8+ elevated andCDs+declined.There was a statistical difference after treatment(P＜0.01).Before treatment,each patient had flare-up 4.5 times annually on average,but only 1.5times after treatment,with a statistical difference(P ＜0.05). Conclusions Cellular immune dysfunction may occurin patients with RGH.Therapy with antiviral drugs and immunomodulators can improvecell-mediated immunity in the patients,and reduce the recurrence of genital herpes. Key words: Recurrentgenital herpes; Cell-mediated immunity; Treatment

Primary immunodeficiency diseases associated with increased susceptibility to viral infections and malignancies

Primary immunodeficiencies (PIDs) are commonly characterized by an increased susceptibility to specific infections and, in certain instances, a higher than usual incidence of malignancies. Although improved diagnosis and early treatment of PIDs have reduced early morbidity and mortality from infection, the development of cancer remains a significant cause of premature death. The emergence of cancer in patients with PIDs often results from impairments in the immune response that lead to weakened surveillance against oncogenic viruses, premalignant or malignant cells, or both. Here we review the clinical and biologic features of several PIDs associated with enhanced susceptibility to viral infections and cancer, including X-linked lymphoproliferative disease; IL-2-inducible T-cell kinase deficiency; epidermodysplasia verruciformis; warts, hypogammaglobulinemia, infections, and myelokathexis syndrome; autosomal recessive hyper-IgE syndrome; X-linked agammaglobulinemia; and common variable immunodeficiency. It is of importance that we gain in-depth insights into the fundamental molecular nature of these unique PIDs to better understand the pathogenesis of virus-associated malignancies and to develop innovative therapeutic strategies.

X‐linked lymphoproliferative syndrome: a genetic condition typified by the triad of infection, immunodeficiency and lymphoma

X-linked lymphoproliferative disease (XLP) is an inherited immunodeficiency characterized by the clinical triad of increased susceptibility to primary Epstein-Barr virus (EBV) infection, dysgammaglobulinaemia and lymphoma. Most cases are caused by germline mutations in the SH2D1A gene, which encodes the adaptor molecule Signalling Lymphocytic Activation Molecule (SLAM)-associated protein (SAP). Recently, a subset of patients with an XLP-like phenotype was found to carry mutations in XIAP, the gene encoding the X-linked inhibitor of apoptosis protein (XIAP). Studies of XLP patients and Sap-/- mice reveal that loss of SAP expression impairs immune cell activities, such as natural killer and CD8+ T cell cytotoxicity, T cell cytokine production, activation-induced cell death, germinal centre formation and natural killer T cell development. Efforts to dissect the diverse roles of SAP and XIAP are enhancing our understanding of immune cell biology and defining how genetic defects in these molecules predispose to EBV-specific as well as more general cellular and humoral immune dysfunction. These studies are also highlighting critical signalling pathways that might be amenable to pharmacological targeting to improve the treatment of XLP and other disorders associated with impaired antiviral and antitumour immunity.

P33 Treatment with Toll-like receptor 4 antagonist restores the inflammatory cellular immune dysfunction in acetaminophen induced acute liver failure mice

IntroductionAcute liver failure (ALF) is a rare, catastrophic syndrome commonly caused by acetaminophen (APAP) that results in the death of about 40% patients. In addition to liver dysfunction, its outcome...

ORIGINAL ARTICLE: The Effect of High Gravidity on the Carcinogenesis of Mammary Gland in TA2 Mice

Citation Wang X, Huang C, Sun B, Gu Y, Cui Y, Zhao X, Li Y, Zhang S. The effect of high gravidity on the carcinogenesis of mammary gland in TA2 mice. Am J Reprod Immunol 2010ProblemSpontaneous breast cancer in Tientsin Albinao 2 (TA2) mice, like human pregnancy‐associated breast cancer (PABC), often occurs in pregnancy and puerperium, especially in mice with high gravidity. We hypothesized that the dysfunction of cellular immunity caused by the increase of 17β‐estradiol (E2) and progesterone (P) might be one of the reasons for carcinogenesis of mammary gland.Method of studyWe investigated the T lymphocyte subsets and the concentration of serum hormone and cytokines in cancer‐bearing, pregnant or postpartum TA2 mice using flow cytometry, chemiluminescent immunoassay, and enzyme‐linked immunosorbent assay (ELISA), respectively.ResultsThe number of T lymphocytes and the concentration of E2, P, interleukin‐2 (IL‐2), IL‐4, and interferon‐gamma (IFN‐γ) changed with the increase of pregnancy and puerperium. During four pregnancies, elevated E2 and P resulted in a decrease in the number of CD3+, CD4+ T lymphocytes, CD4+/CD8+ ratio, and the concentration of IL‐2, IL‐4, and IFN‐γ. Data in the fourth pregnancy were the closest to those of cancer‐bearing mice.ConclusionT lymphocyte subsets and concentration of IL‐2, IL‐4, and IFN‐γ are affected by E2 and P during multiple pregnancy and delivery to some degree, which may contribute to the genesis of spontaneous breast cancer in TA2 mice.

Idiopathic Thrombocytopenic Purpura in a Boy With Ataxia Telangiectasia on Immunoglobulin Replacement Therapy

Ataxia telangiectasia (AT) is an inherited cerebellar degeneration syndrome often associated with immune deficiency, notably, lymphopenia, hypogammaglobulinemia, and cellular immune dysfunction. Although autoimmunity is a common feature of many congenital and acquired immune deficiencies, it has not generally been thought to be associated with AT. We report a 7-year-old boy with AT who developed acute idiopathic thrombocytopenic purpura while on subcutaneous immunoglobulin replacement therapy for hypogammaglobulinemia. He responded promptly to high-dose intravenous immunoglobulin. This case reinforces the notion that one must be observant for autoimmune hematologic conditions in any child with qualitative or quantitative deficiencies in cellular immunity.

CD4+/FOXP3+ Regulatory T Cells in End-Stage Kidney Disease: Molecular Pathways Trough Cell-Cycle Arrest and Apoptosis

CD4 + /FOXP3 + regulatory T cells (Tregs) are essential for the maintenance of self-tolerance, and Tregs defi- ciency results in spontaneous autoimmunity in both mice and humans. The forkhead box P3 (FOXP3) expression is required for both survival of Tregs precursors as well as their function. This suggests that Tregs may use multiple mecha- nisms to limit autoimmunity, and may reflect functional heterogeneity among Tregs subsets that localize to distinct tissue environments. Both cell contact- and cytokine-based immunosuppressive mechanisms would require that Tregs be in close proximity to their targets. The fundamental regulatory activity that can be consistently demonstrated by Tregs in vivo and in vitro has stimulated great interest in developing novel strategies for treating ongoing inflammatory conditions. Patients with end-stage kidney disease (ESKD) are known to display a cellular immune dysfunction. Uremic solutes that accumulate during ESKD may be involved in these processes. In these patients, oxidative stress induced by oxidized LDL (oxLDL) may increase Tregs sensitivity to Fas-mediated apoptosis in part as a consequence of 26S proteasome activation. The 26S proteasome, an ATP-dependent multisubunit protease complex found in the cytoplasm and in the nucleus of all eukaryotic cells, constitutes the central proteolytic machinery of the ubiquitin/proteasome system. Considering the effect of uremia and oxLDL, Tregs from patients with ESKD exhibit early cell-cycle arrest and become apoptotic. These phe- nomena are the consequence of the oxLDL inhibited proteasome proteolytic activity of p27 Kip1 and Bax proteins in Tregs. This may be one mechanistic explanation of the cellular immune dysfunction in patients with ESKD, and may have im- portant implications in clinics, since this response could contribute to the micro-inflammation and atherogenesis encoun- tered in this population.

Influence of CD4+/CD25+ regulatory T cells on atherogenesis in patients with end-stage kidney disease

Atherosclerosis, which is influenced by both traditional and nontraditional cardiovascular risk factors and has been characterized as an inflammatory process, is considered to be the main cause of the elevated cardiovascular risk associated with chronic kidney disease. The inflammatory component of atherosclerosis can be separated into an innate immune response involving monocytes and macrophages that respond to the excessive uptake of lipoproteins and an adaptive immune response that involves antigen-specific T cells. Concurrent with the influx of immune cells to the site of atherosclerotic lesion, the role of the adaptive immune response gradually increases. One of those cells are represented by the CD4+/CD25+ Tregs, which play indispensable roles in the maintenance of natural self-tolerance and negative control of pathological, as well as physiological, immune responses. Altered self-antigens such as oxidized LDLs may induce the development of CD4+/CD25+ Tregs with atheroprotective properties. However, atherosclerosis may be promoted by an imbalance between regulatory and pathogenic immunity that may be represented by the low expression of the forkhead box transcription factor (Foxp3) in CD4+/CD25+ Tregs. Such a defect may break immunologic tolerance and alter both specific and bystander immune suppression, leading to exacerbation of plaque development. Patients with end-stage kidney disease (ESKD) display a cellular immune dysfunction and accelerated atherosclerosis. Uremic solutes that accumulate during ESKD may be involved in these processes. In patients with ESKD and especially in those that are chronically hemodialyzed, oxidative stress induced by oxidized LDLs may increase CD4+/CD25+ Treg sensitivity to Fas-mediated apoptosis as a consequence of specific dysregulation of IL-2 expression. This review will focus on the current state of knowledge regarding the influence of CD4+/CD25+ Tregs on atherogenesis in patients with ESKD, and the potential effect of statins on the circulating number and the functional properties of these cells.

Enfermedad injerto contra huésped asociada a transfusión

Background: Transfusion-associated graft versus host disease (AT-GVDH) is produced by an aggressive host inmune response secondary to the incorporation and proliferation of T lymphocytes in blood products. AT-GVDH affects immunocompromised patients with cellular immune dysfunction, but also immunocompetent persons with certain genetic characteristics. It presents as an acute syndrome that involves skin, gastrointestinal tract, liver and bone marrow. The use of irradiated blood products represents the only therapeutic choice. Objective: To describe a severe and rarely diagnosed pathological condition associated to frequent clinical practice. Case-Report: A 6 months-old child with a severe combined immunodeficiency (pathology with high risk of AT-GVDH) who developed this disease after a filtered red blood cell transfusion. Conclusions: The AT-GVDH is an uncommon iatrogenic and highly lethal complication related to the use of blood products. It implies high degree of clinical suspicion because underlying pathologies of risk may be unknown. The therapy is poor, being prevention the only available alternative. It is fundamental to know the risks and complications in using blood products, in order to determine correctly their indications.