Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the relatively early reconstitution of blood B-lymphocyte counts observed in patients treated with bone marrow transplantation (BMT), these patients undergo a prolonged phase of humoral immunodeficiency. Adhesion molecules perform relevant functions in many cell types. The present study examines the expression of several adhesion molecules on human B lymphocytes newly formed after BMT. Blood B cells from 38 patients were studied by flow cytometry and three-color analysis. Blood CD5- B lymphocytes obtained at an early stage after BMT (2 to 4 months) showed a markedly low expression of the adhesion molecules CD54, CD44, CD11a, and CD62L. However, these cells exhibited a normal expression of other molecules including CD29, CD19, CD20, and DR. This deficiency was progressively corrected, reaching normal levels in the late post-BMT period (12 to 15 months). In contrast, CD54, CD44, CD11a, and CD62L expression on the patients' CD5+ B lymphocytes was found to be consistently normal. Deficient adhesion molecule expression on CD5- B cells in the early post-BMT period was similarly observed in patients treated with either an allo-BMT (n = 24) or an auto-BMT (n = 14). Because the post-BMT period mimics normal ontogeny, adhesion molecule expression was also investigated in cord-blood B lymphocytes. Cord-blood CD5- B lymphocytes, in contrast to CD5+, also expressed CD54, CD44, CD11a, and CD62L at levels much lower than those found in normal adults. Present data suggest that progressive expression of CD54, CD44, CD11a, and CD62L seems to be a part of the maturational program of CD5- B lymphocytes during both post-BMT and normal development periods. This observation may help to explain the humoral immunodeficiency observed in both conditions.
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PMID:Deficient expression of adhesion molecules by human CD5- B lymphocytes both after bone marrow transplantation and during normal ontogeny. 878 29

Hepatitis C virus (HCV) infection may be complicated by non-Hodgkin's lymphoma through yet unknown pathogenetic mechanisms. We describe the case of a patient with HCV-related cirrhosis who developed a primary effusion lymphoma (PEL) of Burkitt's type confined to the peritoneal cavity, in the absence of immunodeficiency or autoimmunity. Paracentesis followed by immunophenotyping, karyotyping, and molecular studies allowed us to diagnose a small noncleaved B-cell lymphoma (CD20+, CD24+, CD10+, CD5-, CD23-, lambda+) with the t(8;22) (q24;q11) translocation and clonal rearrangement of the immunoglobulin heavy chain gene. HCV-RNA, Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus were not identified within lymphoma cells. The finding of HCV-RNA in the ascitic fluid suggests a link between HCV and development of lymphoma with HCV playing the role of persistent antigenic stimulation to intraperitoneal B-cell clonal expansion(s).
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PMID:Primary effusion Burkitt's lymphoma with t(8;22) in a patient with hepatitis C virus-related cirrhosis. 941 5

CD43 (leukosialin), a sialylated glycoprotein expressed on the surface of most hematopoietic cells, has been implicated in cell adhesion and signaling. However, its precise physiological function remains unclear. We used mouse CD43 (mCD43)-immunoglobulin enhancer-transgenic (TG) mice to study the role of mCD43 in vivo. Previous work revealed that mCD43 expression on mature B cells in these mice resulted in immunodeficiency to T-dependent (TD) antigens (Ag), possibly by impairing B-T cell interactions. In the present study we have immunized the TG mice with the T-independent (TI) Ag fluorescein-(Fl) lipopolysaccharide (LPS) (TI type 1 Ag) and Fl-Ficoll (TI type 2 Ag). Surprisingly, the mCD43-Ig enhancer expressing mice were impaired in their ability to mount humoral responses to both Fl-LPS and Fl-Ficoll, and had decreased numbers of cells responding to Ag in vivo. Flow cytometric analysis was performed on peritoneal B-1 cells, a population which often plays a major role in humoral responses to TI Ag such as bacterial Ag. This analysis revealed similar B220, IgM and CD5 expression patterns for the TG and nontransgenic (NTG) B-1 cells. In addition, purified peritoneal B-1 cells from TG and NTG mice were able to respond to LPS. Stimulation of splenic B cells in vitro with Fl-LPS and Fl-Ficoll revealed that, in contrast to NTG B cell responses, TG B cell responses could not be enhanced by co-culture with T cells. However, soluble T cell factor enhancement of the TG B cell responses was normal. These data suggest that the mCD43 expression on B cells may inhibit cell interactions that are important for enhanced TI Ag responses. The anti-adhesive forces of mucins in general may thus be critical in regulating both TD and TI humoral responses.
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PMID:Expression of mouse CD43 in the B cell lineage of transgenic mice causes impaired immune responses to T-independent antigens. 934 53

CD8+ lymphocytes have been subdivided into CD8alphabeta and CD8alpha alpha populations in the peripheral blood lymphocytes (PBL) of humans and in several animal species but have not yet been investigated in cats. Feline immunodeficiency virus (FIV) causes progressive immunological disorders similar to human AIDS. In this study, we analysed CD8+ cells in PBL of FIV-infected or uninfected cats by two-colour flow cytometric analysis. In specific pathogen-free adult cats, feline CD8alpha+beta(high) cells were observed but CD8alpha+beta- cells were not found in significant numbers. On the other hand, not only CD8alpha+beta(high) but also CD8alpha+beta- and CD8alpha+beta(low) cell populations were observed in cats chronically infected with FIV. The expansion of the CD8beta(low) or CD8beta- subpopulations resulted in the apparent differences in CD4/CD8 ratios depending on the anti-CD8 MAb used. These findings suggest a need to reconsider the CD4/CD8 ratio in studies of FIV infection. Furthermore, we found that the CD8alpha+beta- cell population expressed CD5 at a low level.
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PMID:Expansion of CD8alpha+beta- cells in cats infected with feline immunodeficiency virus. 946 Sep 28

There is evidence indicating that autoreactive B cells constitute a substantial part of the B cell repertoire. This autoreactive repertoire secretes the so-called natural autoantibodies characterized by their broad reactivity mainly directed against well-conserved public epitopes. Their germinal origin is suggested by their early appearance during ontogeny, their expression of cross-reactive idiotopes, and structural studies of their sequence. As for the physiological role of the repertoire, it may play a major role as a first barrier of defense. It is presently unknown whether these polyreactive B cells could constitute a pre-immune template which, through an antigen-driven process, may be involved in the production of immune high-affinity antibodies. This autoreactive B cell repertoire frequently undergoes malignant transformation, although there is controversy concerning the reasons accounting for this. It has been postulated that the continuous challenge of this autoreactive repertoire by self-antigens could create propitious conditions for malignant transformation to occur. However, this hypothesis still needs to be substantiated. Chronic lymphocytic leukemia (CLL), the most frequent form of leukemia in western countries, is characterized by constant expression of the CD5 marker and low expression of surface membrane immunoglobulin (Ig) in B lymphocytes. CLL B lymphocyte is frequently committed for natural autoantibody secretion. Despite expressing the Epstein-Barr virus (EBV) receptor CLL B cells cannot be infected by the EBV virus, they overexpress the bcl-2 protein and they are unable to adequately respond when stimulated through the B cell receptor pathway. Autoimmune-associated phenomena are frequently observed in B-cell CLL. These autotoxic manifestations are mainly directed against hematopoietic cells. In most cases, autoantibodies against red blood cells are warm reactive polyclonal IgG. Immune thrombocytopenia is observed in about 2% of cases, but higher frequencies of increased platelet associated Igs have been reported. Pure red cell aplasia and autoantibodies against neutrophils are only rarely observed. This pattern is similar to that observed in primary immunodeficiency syndromes, in which immune thrombocytopenia, autoimmune hemolytic anemia, and pure red cell aplasia are frequently observed. The potential role of T cell defects in inducing autoimmune complications in B-cell CLL has been stressed by recent publications showing increased frequency of autoimmune hemolytic anemia in patients treated with purine nucleoside analogues. However, evidence is presently scarce concerning a functional impairment of T cells after administration of these drugs.
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PMID:Basic biology of autoimmune phenomena in chronic lymphocytic leukemia. 948 25

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by mutations of Bruton tyrosine kinase (Btk); Btk plays an essential role in the development of mature B cells. However, small numbers of B cells ("leaky B cells") are present in the peripheral blood of most XLA patients. In this study, we analyzed the function of these leaky B cells obtained from XLA patients. Enough numbers of B cells were available for analysis from five of nine XLA patients originally screened. Sequence analysis revealed missense mutations of Btk in four of the five XLA patients. No mutation was found in the coding region of Btk in one patient. Western blotting and/or flow cytometric analysis failed to detect Btk protein in all five patients. B cells isolated from peripheral blood of these XLA patients were CD5-, CD20+, CD19+, and CD21-. If stimulated with anti-CD40 and IL-4, XLA B cells proliferated normally and produced significant amounts of IgE. Anti-CD40 stimulation of XLA B cells resulted in normal expression of CD23. In addition, three of the five XLA patients studied were immunized with bacteriophage phiX174 and produced low but detectable levels of antiphage-specific Ab. Similarly, X-linked immunodeficiency mice, which carry a missense mutation in Btk, produced substantial amounts of antiphage Ab. These results indicate that CD40 signaling is intact in B cells lacking demonstrable Btk, and that leaky B cells in XLA patients can proliferate, undergo isotype switching, and differentiate into specific Ab-producing cells.
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PMID:Functional analysis of peripheral blood B cells in patients with X-linked agammaglobulinemia. 978 Jan 59

Over the past year, progress has been made in understanding of the physiology and disease associations of CD5+ (B1) B cells, although their exact role in pathogenesis remains unclear. Earlier studies on the negative function of CD5 within the B-cell receptor complex have been substantiated, and it seems likely that soon the signaling pathways used by this coreceptor will be elucidated. Progress in diagnosis, physiology, and etiopathogenesis of CD5+ malignancies has been made, particularly in B-cell chronic lymphocytic leukemia. The low-level expression of surface immunoglobulin has been explained by the mutations that occur in the associated CD79b. Two new potential tumor-suppressor genes have been identified in the hot spot of chromosome 13q, which provides an exciting step forward in understanding of the etiopathogenesis of some B-cell chronic lymphocytic leukemia. Activated signal transducers for activation of transcription factors molecules have been shown to be phosphorylated on different amino acids in B1 and chronic lymphocytic leukemia tumors, although the significance of this is, as yet, unclear. Finally, aberrant expression of CD40L by chronic lymphocytic leukemia T cells may contribute to the immunodeficiency that develops in these patients.
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PMID:CD5 B cells and B-cell malignancies. 991 51

The phenotypic analysis of human umbilical cord blood (CB) mononuclear cells is important to study their maturity and differentiation regarding their transplantable capacity. In this work we have studied differential expression of B cell antigens on CD5-/HLA-DR+ B cells (B1b, B2) and CD5+/HLA-DR+ cells (Bla) from the CB (n=6) and adult peripheral blood (PB) (N=6). CD5-PE, HLA-DR-PerCP and FITC labelled anti-B cell MoAb panel of the 6th International Workshop on Human Differentiation Antigens were used for detection of B cell subpopulations. FacsCalibur (B-D) flow cytometer was used for evaluation of samples. CB Bla (CD5/HLA-DR++) cells proved to be positive with CD9, CD19, CD20, CD21, CD22, CD23, CD24, CD32, CD39, CD45RA, CD76, CD79, MHC-II, IgM and anti Ig light chains MoAbs. CB B1b (CD5-/HLA-DR+) cells reacted with CD9, CD19, CD20, CD21, CD22, CD23, CD24, CD32, CD39, CD45RA, CD79, MHC-II, and IgM MoAbs. PB B cells (B2) expressed CD19, CD20, CD21, CD22, CD24, CD32, CD37, CD39, MHC-II and CD79 Ags. Unlike to the PB the CB B lymphocytes proved to be predominantly B1 cells representing a new-born B cell repertoire. Besides expressing many B cell antigens both the CB Bla and B1b cells showed CD9+, CD45RA+, IgM+ immature, "naive" B cell phenotype. Functionally, B1 cells are capable producing polyreactive IgM and natural autoantibodies but not IgG. This antibody profile might be insufficient regarding the recipient humoral immune defense result in more severe immunodeficiency after CB transplantation.
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PMID:Immunophenotypic characterisation of cord blood B-lymphocytes. 991 47

To identify potential roles of cytokines in retroviral pathogenesis, we used reverse transcription-quantitative competitive polymerase chain reaction (RT-qcPCR) assays to characterize mRNA levels of 19 different lymphokines, chemokines, monokines and hematopoietic growth factors in three feline cell lines productively infected with subgroup A feline leukemia virus (FeLV-A) or various feline immunodeficiency virus (FIV) strains. Infection of a CD8+, CD5- large granular lymphocyte (LGL) cell line with FeLV-A activated expression of interleukin-7 (IL-7), induced modest (4-fold) increases in granulocyte/macrophage colony-stimulating factor (GM-CSF) and leukemia inhibitory factor (LIF) transcripts, and decreased transforming growth factor-beta (TGF-beta) mRNA (4-fold). The LGL cells were not susceptible to infection by FIV. Infection of MYA-1 cells, a CD4+ T-lymphoblastoid cell line, with FeLV-A activated expression of macrophage inflammatory protein-1alpha (MIP-1alpha), increased transcript levels of GM-CSF (8-fold), macrophage CSF (M-CSF) (16-fold) and stem cell factor (SCF) (250-fold), and decreased (4-fold) expression of IL-10 and tumor necrosis factor-alpha (TNF-alpha). Productive infection with four different FIV molecular clones caused progressive MYA-1 cell death; however, the mRNA expression profiles were unchanged except for 2- to 4-fold increases in M-CSF and 16- to 500-fold increases in SCF. Thus, FIV-induced MYA-1 cytopathicity was not associated with dysregulation of pro-apoptotic or survival factor transcript levels. Lastly, productive infection of PNI cells, a marrow-derived fibroendothelial cell line, with FeLV-A or any of three FIV strains induced 4-fold higher levels of IL-12p40 transcripts and variably higher levels (4- to 64-fold) of GM-CSF. Two viral strains, the FIV-14 molecular clone and the clinical isolate FIV-5122, caused syncytia formation and unique activation of IL-1beta and stromal cell-derived factor-1 (SDF-1) expression, suggesting a potential role for those factors in viral spread and/or cytopathicity. In addition, infection with FIV-5122, but not the other FIV strains or FeLV-A, induced significant increases in mRNA levels of the hematopoietic inhibitors TNF-alpha and MIP-1alpha, along with increased concentrations of soluble proteins in culture supernatants. Consistent with this, supernatant from FIV-5122 infected PNI cells suppressed hematopoietic progenitor growth in colony assays, compared to supportive activities in supernatants from other infected or uninfected PNI cell cultures. Together, these data demonstrate that feline retroviruses alter cytokine mRNA levels in general and strain-specific patterns. These changes may result in specific alterations in cell function and contribute to retroviral pathogenesis. Our observations provide a basis for directed studies of candidate factors within the hematopoietic, thymic and lymphoid microenvironments.
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PMID:The effects of feline retroviruses on cytokine expression. 1062 77

Castleman's disease (CD) is a rare atypical lymphoproliferative disorder whose morphology, soon after the original presentation of Castleman et al., has been definitely subdivided in a hyaline vascular (HV) and plasma cell (PC) histopathological pattern, with intermediate variants. The former occurs much more frequently than the latter and is usually localized to the mediastinum or pulmonary hilum. The latter involves lymph nodes separately or in aggregations and often displays multicentricity with systemic symptoms including autoimmune phenomena and aggressive course. Infections are the most frequent causes of patient demise in these cases, followed by malignancies such as Kaposi's sarcoma, malignant lymphoma or epithelial neoplasia. Increase of follicular dendritic reticulum cells (FDRC), often dysplastic, in the germinal center (GC) and marginal zone (MZ), broad MZ expansion with prominence of immunophenotypically aberrant B cells (Ki B3-negative, CD5-positive), possible predominance of paracortical plasma cells often with clusters of clonal l-light chain restricted plasma cells, increase of paracortical plasmacytoid monocytes, represent common hallmarks of CD. However, small hyalinized and hypervascular GCs with hypervascular interfollicular stroma and sinus effacement are common features of the HV variant, whereas hyperplastic GCs with plasma cell aggregates in lymph node paracortex and partially spared sinuses are characteristic features of the PC variant. The frequent concomitance of the HV and PC types at separate sites, together with transient morphological patterns from one type to the other and from the localized to multicentric form during the course of the disease, along with B and T cell impaired functions, with frequent development of autoantibodies, have suggested that CD is a single disorder related to immune dysregulation. A key event in the pathogenesis of CD has been recently suggested to be an abnormal production of a B cell growth factor, such as IL-6, leading to lymphoproliferation and plasma cell differentiation and being involved in the oncogenesis of plasmacytoma. In this event, Kaposi's sarcoma associated virus (HHV-8), which has been found in many cases of CD, especially in the multicentric form, could play a crucial role both in producing IL-6 and releasing angiogenic factors. A possible differentiation block may lead to the development of a malignant lymphoma. Kaposi's sarcoma or other malignant neoplasias can be supposed to be consequences of the immunodeficiency typical of CD.
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PMID:Castleman's disease. 1065 69


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