Immune Defect (immune + defect)

Distribution by Scientific Domains


Selected Abstracts


Post-surgical irradiation causes cellular immune suppression in patients with breast cancer

EUROPEAN JOURNAL OF CANCER CARE, Issue 3 2009
G.V. KOUKOURAKIS md
According to several studies, even the locoregional irradiation of patients with carcinoma can cause a severe and rather alarming cellular immune defect. We thus designed a prospective research in order to study the effect of post-operative irradiation on cellular immunity in patients suffering from breast cancer. In 35 patients with breast cancer who required post-operative irradiation, four blood samples were taken at indicated point times. Nineteen out of 35 patients received post-surgical chemotherapy before irradiation. The total lymphocytes as well as CD4 and CD8 subpopulations were measured by using flow cytometry analysis. The mean T-lymphocyte (Tol) count dropped from 1487.77 to 1227.91 (P = 0.0013) and the CD4+ count from 674.17 to 580.91 (P = 0.0189). The mean value of CD8+ dropped from 421.31 to 314.00 (P = 0.0003). Moreover, a statistically significant difference regarding the pattern of temporal change was observed between a group of patients that received irradiation only and a group that received radiation therapy (RT) with chemotherapy (P -values 0.0015, 0.01 and 0.092 for Tol, CD4+ and CD8+ respectively). The group of patients that received RT only presented a more rapid decrease of Tol concerning the decrease observed in the group that underwent chemotherapy and RT. [source]


Molecular and cellular pathogenesis of X-linked lymphoproliferative disease

IMMUNOLOGICAL REVIEWS, Issue 1 2005
Kim E. Nichols
Summary:, X-linked lymphoproliferative disease (XLP) is an inherited immune defect caused by mutations in the Src homology 2 domain-containing gene 1A, which encodes the adapter protein, signaling lymphocytic activation molecule (SLAM)-associated protein (SAP). SAP is expressed in T cells, natural killer (NK) cells, and NKT cells, where it binds to the cytoplasmic domain of the surface receptor SLAM (CD150) and the related receptors, 2B4 (CD244), CD84, Ly9 (CD229), NK-T-B-antigen, and CD2-like receptor-activating cytotoxic T cells. SAP also binds to the Src family tyrosine kinase Fyn and recruits it to SLAM, which leads to the generation of downstream phosphotyrosine signals. While the roles of the SLAM family receptors are only beginning to be understood, experiments suggest that these molecules regulate important aspects of lymphocyte function, such as proliferation, cytokine secretion, cytotoxicity, and antibody production. Thus, in XLP patients who lack functional SAP, the SLAM family receptors may not signal properly. This property likely contributes to the phenotypes of XLP, including fulminant infectious mononucleosis, lymphoma, and hypogammaglobulinemia. Further studies of SAP and the SLAM family receptors will provide insights into XLP and elucidate the signaling events regulating lymphocyte ontogeny and function. [source]


New proteomic approaches for biomarker discovery in inflammatory bowel disease

INFLAMMATORY BOWEL DISEASES, Issue 7 2010
Giulia Roda MD
Abstract There is an increasing interest in the discovery of new inflammatory bowel disease (IBD) biomarkers able to predict the future patterns of disease and to help in diagnosis, treatment, and prognosis. A biomarker is a substance that can be measured biologically and is associated with an increased risk of the disease. Biomarkers can be a genetic testing factor or proteins in biological samples such as serum, plasma, and cellular subpopulations. All of them should be studied to find out their utility in the management of IBD. Ulcerative colitis and Crohn's disease are relapsing and remitting chronic IBDs characterized by a global immune defect. The gold standard of their diagnosis is histological evaluation performed during endoscopic procedures. Several studies have focused on the identification and combination of less invasive diagnostic serum biomarkers. Nowadays, diagnostic serum tests are not able either to determine whether and when the relapse will occur once the disease is in remission state or to select a patient phenotype more responsive to a specific therapy and more susceptible to different types of complication. In this review we analyze and report the current understanding in IBD biomarkers and discuss potential future biomarkers and new developments of proteomics, such as subproteomics, as an innovative approach for the classification of patients according to their pattern of protein expression. (Inflamm Bowel Dis 2010) [source]


Oseltamivir Treatment Prevents the Increased Influenza Virus Disease Severity and Lethality Occurring in Chronic Ethanol Consuming Mice

ALCOHOLISM, Issue 8 2010
Ryan A. Langlois
Background:, Chronic consumption of ethanol (EtOH) is well recognized to lead to defective innate and adaptive immune responses and increase the severity of pulmonary infections. Our own studies have demonstrated that chronic EtOH consumption decreases CD8 T-cell immunity to influenza virus infections (IAV) leading to severe infections and mortality. Interestingly, antiviral treatment of IAVs has been shown to be compromised in mice and humans that are immuno-deficient. It is known that EtOH can alter the pharmacokinetics of antivirals. Therefore, the effectiveness of influenza antiviral therapy during chronic ethanol consumption remains in question. Methods:, BALB/c mice were placed on 18% (w/v) EtOH in their drinking water for 8 weeks. Chronic EtOH consuming and water controls were then treated with 10 mg/kg oseltamivir orally and infected intranasally with influenza virus 4 hours post-oseltamivir treatment. The mice were then treated with oseltamivir twice daily until day 7 postinfection. Influenza disease severity was measured by morbidity and mortality, pulmonary viral titers, and histology. Results:, Chronic EtOH consuming mice infected with IAV and treated with oseltamivir have decreased morbidity and mortality, pulmonary viral titers, and pulmonary pathology compared to untreated EtOH mice. Conclusions:, Despite the severe immune defect seen in chronic EtOH mice as well as the potential for EtOH to inhibit the conversion of oseltamivir into an active form, treatment with oseltamivir reduces viral shedding as well as disease severity. These data suggest that the combination of a limited adaptive immune response plus the anti-IAV drug oseltamivir is sufficient to curb high mortality and mediate resolution of IAVs in mice chronically consuming ethanol. [source]


Autoimmune cytopenia does not predict poor prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2003
Mouhammed J. Kyasa
Abstract Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is characterized by an acquired immune defect that can cause autoimmune complications, including anemia and thrombocytopenia. We conducted an observational study of the epidemiology, clinical presentation and significance of autoimmune complications of CLL/SLL in 132 patients from a large population (>45,000 veterans), in which at least 90% of patients with CLL/SLL have been previously identified. Over a period of 12.5 years, 12 patients (9.1%) had autoimmune complications; of these, 6 (4.5%) had autoimmune hemolytic anemia (AIHA), 5 (3.8%) had immune thrombocytopenia (ITP), and 1 (0.8%) had pure red blood cell aplasia (PRBA). All 6 cases of AIHA had a positive direct immunoglobulin test for IgG and C3d. In 6 patients, CLL/SLL was an incidental finding at the time of presentation with autoimmune cytopenia. Nine out of 10 patients responded to immunosuppressive therapy, which was complicated by serious infection in 7 cases, one of which was fatal. The major cause of mortality in patients with autoimmune complications of CLL/SLL was secondary malignancy. Survival of patients with immune cytopenia was not significantly different from CLL/SLL patients without immune cytopenia. Among patients with anemia or thrombocytopenia, mortality was significantly higher in those with bone marrow failure compared to an autoimmune etiology. We show that in a non-referred population with a high incidence of CLL/SLL, autoimmune cytopenia can occur early in the natural history of the disease. These data suggest that the Rai and Binet classifications for CLL need to be modified for patients with autoimmune cytopenia. Am. J. Hematol. 74:1,8, 2003. Published 2003 Wiley-Liss, Inc. [source]


CD40L is Critical for Protection from Demyelinating Disease and Development of Spontaneous Remyelination in a Mouse Model of Multiple Sclerosis

BRAIN PATHOLOGY, Issue 1 2000
Kristen M. Drescher
Theiler's murine encephalomyelitis virus (TMEV) induces acute neuronal disease followed by chronic demyelination in susceptible strains of mice. In this study we examined the role of a limited immune defect (deletion or blocking of CD40 ligand [CD40L]) on the extent of brain disease, susceptibility to demyelination, and the ability of demyelinated mice to spontaneously remyelinate following TMEV infection. We demonstrated that CD40L-dependent immune responses participate in pathogenesis in the cerebellum and the spinal cord white matter but protect the striatum of susceptible SJL/J mice. In mice on a background resistant to TMEV-induced demyelination (C57BL/6), the lack of CD40L resulted in increased striatal disease and meningeal inflammation. In addition, CD40L was required to maintain resistance to demyelination and clinical deficits in H-2b mice. CD40L-mediated interactions were also necessary for development of protective H-2b -restricted cytotoxic T cell responses directed against the VP2 region of TMEV as well as for spontaneous remyelination of the spinal cord white matter. The data presented here demonstrated the critical role of this molecule in both antibody- and cell-mediated protective immune responses in distinct phases of TMEV-mediated pathology. [source]


Translational Mini-Review Series on Immunodeficiency: Molecular defects in common variable immunodeficiency

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2007
C. Bacchelli
Summary Common variable immunodeficiency (CVID) is a primary immunodeficiency that typically affects adults and is characterized by abnormalities of quantative and qualitative humoral function that are heterogeneous in their immunological profile and clinical manifestations. The recent identification of four monogenic defects that result in the CVID phenotype also demonstrates that the genetic basis of CVID is highly variable. Mutations in the genes encoding the tumour necrosis factor (TNF) superfamily receptors transmembrane activator and calcium-modulating ligand interactor (TACI) and B cell activation factor of the TNF family receptor (BAFF-R), CD19 and the co-stimulatory molecule inducible co-stimulator molecule (ICOS) all lead to CVID and illustrate the complex interplay required to co-ordinate an effective humoral immune response. The molecular mechanisms leading to the immune defect are still not understood clearly and particularly in the case of TACI, where a number of heterozygous mutations have been found in affected individuals, the molecular pathogenesis of disease requires further elucidation. Together these defects account for perhaps 10,15% of all cases of CVID and it is highly likely that further genetic defects will be identified. [source]


High-frequency haplotypes in the X chromosome locus TLR8 are associated with both CD and UC in females

INFLAMMATORY BOWEL DISEASES, Issue 3 2009
Masayuki Saruta MD
Abstract Background: TNF-, and IL-1 have been associated with mucosal inflammation in both Crohn's disease (CD) and ulcerative colitis (UC). Innate immune defects have been associated with CD, specifically CARD15/NOD2. Recently, Toll-like receptor 8 (TLR8) signaling has been shown to enhance generation of both cytokines. Interestingly, TLR8 is located on the X chromosome and inflammatory bowel disease (IBD) has been associated with abnormalities of the X chromosome. The aim was to test whether TLR8 haplotypes are associated with IBD. Methods: Subjects (735 CD, 343 UC, 245 controls) were genotyped. Single nucleotide polymorphisms (SNPs) were chosen to tag common Caucasian haplotypes. Results: Both "risk (H4)" and "protective (H1)" TLR8 haplotypes were observed associated with CD in females. Eighteen percent of CD females had H4 compared with 9% of controls (P = 0.02). Fifty-nine percent of CD females had H1 compared with 72% of controls (P = 0.01). H1 was also negatively associated with UC in females (59% of UC, 72% of controls P = 0.03). Diplotype analysis of CD, UC, and all IBD in females revealed that 2 protective haplotypes (H1/H1) had a markedly diminished odds ratio, 0.4,0.5. The presence of a risk haplotype (H4 / not H1) had a significantly increased odds ratio, 2.0,2.2. Thus, the risk for IBD was 4,5 times higher in females with 1 risk haplotype than with the protective/protective diplotype. Conclusions: TLR8 is an X-linked IBD susceptibility gene with both common predisposing and protecting haplotypes. These associations further emphasize the importance of genetic variation in innate immunity as determinants, not only of CD, but of UC as well. (Inflamm Bowel Dis 2008) [source]


Laboratory Models Available to Study Alcohol-Induced Organ Damage and Immune Variations: Choosing the Appropriate Model

ALCOHOLISM, Issue 9 2010
Nympha B. D'Souza El-Guindy
The morbidity and mortality resulting from alcohol-related diseases globally impose a substantive cost to society. To minimize the financial burden on society and improve the quality of life for individuals suffering from the ill effects of alcohol abuse, substantial research in the alcohol field is focused on understanding the mechanisms by which alcohol-related diseases develop and progress. Since ethical concerns and inherent difficulties limit the amount of alcohol abuse research that can be performed in humans, most studies are performed in laboratory animals. This article summarizes the various laboratory models of alcohol abuse that are currently available and are used to study the mechanisms by which alcohol abuse induces organ damage and immune defects. The strengths and weaknesses of each of the models are discussed. Integrated into the review are the presentations that were made in the symposium "Methods of Ethanol Application in Alcohol Model,How Long is Long Enough" at the joint 2008 Research Society on Alcoholism (RSA) and International Society for Biomedical Research on Alcoholism (ISBRA) meeting, Washington, DC, emphasizing the importance not only of selecting the most appropriate laboratory alcohol model to address the specific goals of a project but also of ensuring that the findings can be extrapolated to alcohol-induced diseases in humans. [source]