Papers by Paloma Perez-Aciego
The Journal of Rheumatology
To determine whether mannose binding lectin (MBL) polymorphisms are associated with clinical char... more To determine whether mannose binding lectin (MBL) polymorphisms are associated with clinical characteristics and with susceptibility to systemic lupus erythematosus (SLE) in women from the Canary Islands, Spain. MBL alleles and genotypes were determined by polymerase chain reaction in 89 female patients and 188 female controls. No differences in the allelic or genotypic frequencies were observed between patients and controls. Anti-U1RNP autoantibodies were less frequent in association with mutated alleles (p = 0.037), and in association with MBL deficient genotypes, although this association was not statistically significant. The patients with low or nonproducer genotypes exhibited a decreased frequency of anti-Sm antibodies (p = 0.059). A nonsignificant trend toward lower prevalence of anti-Sm and anticardiolipin antibodies in association with both mutated alleles and low or nonproducer genotypes was also observed. The prevalence of more than one autoantibody was lower in associati...
Immunodeficiency reviews, 1990
The T-cell receptor (TCR) for antigen is a complex consisting of at least seven polypeptides chai... more The T-cell receptor (TCR) for antigen is a complex consisting of at least seven polypeptides chains. Two chains form the clonotypic heterodimer, which determines antigen-specificity. The other five constitute the monomorphic CD3 components, which are thought to be involved in signal transduction. We have reported a familial defect in the surface expression of the TCR/CD3 complex on otherwise phenotypically normal T lymphocytes. As a consequence of the surface defect, an impaired T-lymphocyte activation through the TCR and CD3 complex by both antigens and mitogens is observed in this type of immunodeficiency (ID) for which we propose the name TCR ID. In contrast, normal proliferative responses were recorded to TCR-independent activation or proliferation signals (i.e: anti-CD2, phorbol esters and IL-2). We believe that other ID with similar clinical and immunological characteristics, described before the general availability of monoclonal antibodies, may have also been TCR ID. Severe ...
Laboratory investigation; a journal of technical methods and pathology, 1991
Necropsic lymphoid tissues obtained from an infant with a novel type of immunodeficiency consisti... more Necropsic lymphoid tissues obtained from an infant with a novel type of immunodeficiency consisting of a peripheral blood T lymphocyte antigen receptor (TCR) surface expression defect, were analyzed by immunohistochemistry for the expression of various TCR-associated epitopes. The work was aimed to characterize the biochemical basis of this kind of disorder and confirm the defect in different lymphoid tissues. Within an assessed lymphoid depletion, the patient's tissues showed a normal expression of several TCR epitopes (those associated to CD3 epsilon, CD3 delta and the clonotypic -Ti- alpha and beta chains). In contrast, the expression of the epitopes recognized by the monoclonals OKT3, WT31, and BMA031 was severely diminished. Our results therefore support that CD3 epsilon, CD3 delta, Ti alpha and Ti beta are probably not involved in this type of immunodeficiency, and strongly suggest that CD3 gamma (forming part of the epitope recognized by OKT3) may rather be the affected c...
Pediatrics, 1989
form. This classificatioa means that the insured is covered only for claims arising and reported ... more form. This classificatioa means that the insured is covered only for claims arising and reported duringthe policy year for which a pren'ium has been paid" When the policy is terminate4 any further claims reported will not be covered unless the insured purchases a reporting endorsement, commonlY hnown as the "tail." The price of the "tail" is variable according to insurer and ean amount to seveial thousand dollars' Thus, the resident is faced with the dile-a of :going bare," thus riekilg his or her personal assets, present and future, or purchasing expensive "tail' coverage for claims yet unreportrd at the time he or she concludes moonlighting and/or residency. Furthermore, failute to purchase "tail" coverage may impair his or her ability to secure professional liability insurance when he or she commences practice. Residents would do well to read and understand fully
Gastroenterology, 1991
Gut epithelial cell autoantibodies have been considered a hallmark of autoimmune enteropathy, a d... more Gut epithelial cell autoantibodies have been considered a hallmark of autoimmune enteropathy, a disorder occurring in children with protracted diarrhea of unknown etiology. Four patients (two male and two female) with such autoantibodies were studied. Immunofluorescence analysis showed two different disjunctive staining patterns: complement-fixing apical (three of four) and cytoplasmic (the remaining fourth one), which are shown to be directed against different structures. All three patients positive for complement-fixing apical gut epithelial cell autoantibodies had abnormal T-cell responses in vitro, one of them with an immunoglobulin G2 immunoglobulin deficiency and another with an immunoglobulin A deficiency. An immunoglobulin A deficiency without T-cell alterations was also diagnosed in the cytoplasmic gut epithelial cell autoantibody-positive patient. These findings suggest that different immunologic alterations (either a T-cell abnormality or immunoglobulin deficiency) may fa...
Blood, 2004
Excessive proliferation of immune cells and vascular smooth myocytes (VSMCs) contributes to ather... more Excessive proliferation of immune cells and vascular smooth myocytes (VSMCs) contributes to atherosclerosis. We have previously shown that whole-body inactivation of the growth suppressor p27 exacerbates atherosclerosis in apolipoprotein E-null mice (apoE–/–), and this correlated with increased proliferation of arterial macrophages and VSMCs. In the present study, we postulated that targeted disruption of bone marrow (BM) p27 is sufficient to enhance arterial macrophage proliferation and atherosclerosis. To test this hypothesis, sublethally irradiated apoE–/– mice with an intact p27 gene received a BM transplant from either apoE–/– or p27–/–apoE–/– doubly deficient donor mice and challenged with a high-cholesterol diet. Compared with mice that received an apoE–/– BM transplant, reconstitution with p27–/–apoE–/– doubly deficient marrow increased the expression of proliferating cell nuclear antigen in neointimal macrophages and accelerated aortic atherosclerosis, and this correlated w...
PLOS ONE, 2016
B-cell chronic lymphocytic leukemia (CLL) remains an incurable disease, and despite the improveme... more B-cell chronic lymphocytic leukemia (CLL) remains an incurable disease, and despite the improvement achieved by therapeutic regimes developed over the last years still a subset of patients face a rather poor prognosis and will eventually relapse and become refractory to therapy. The natural rotenoid deguelin has been shown to induce apoptosis in several cancer cells and cell lines, including primary human CLL cells, and to act as a chemopreventive agent in animal models of induced carcinogenesis. In this work, we show that deguelin induces apoptosis in vitro in primary human CLL cells and in CLL-like cells from the New Zealand Black (NZB) mouse strain. In both of them, deguelin dowregulates AKT, NFκB and several downstream antiapoptotic proteins (XIAP, cIAP, BCL2, BCL-X L and survivin), activating the mitochondrial pathway of apoptosis. Moreover, deguelin inhibits stromal cell-mediated c-Myc upregulation and resistance to fludarabine, increasing fludarabine induced DNA damage. We further show that deguelin has activity in vivo against NZB CLLlike cells in an experimental model of CLL in young NZB mice transplanted with spleen cells from aged NZB mice with lymphoproliferation. Moreover, the combination of deguelin and fludarabine in this model prolonged the survival of transplanted mice at doses of both compounds that were ineffective when administered individually. These results suggest deguelin could have potential for the treatment of human CLL.
American Journal of Nephrology, 1995
American Journal of Nephrology, 1995
American Journal of Nephrology, 1995
American Journal of Nephrology, 1995
Journal of Experimental Medicine, 1991
Perez-Aciego et al .
European Journal of Immunology, 1990
B lymphocytes require appropriate T lymphocyte cooperation to synthesize immunoglobulins (Ig). Su... more B lymphocytes require appropriate T lymphocyte cooperation to synthesize immunoglobulins (Ig). Such interaction presumably takes place after engagement of the T cell receptor (TcR) by antigen. The present work addresses B lymphocyte function (and phenotype) in a novel type of immunodeficiency which is characterized by a TcR expression defect. In contrast to expectations, the two affected siblings that were studied displayed normal in vivo antibody responses to both endogenous and exogenous protein antigens. However, they showed impaired responses to certain polysaccharide antigens together with a selective IgG2 deficiency. These results suggest that some polysaccharide responses may be more T cell dependent than previously suspected, and support the notion that T cell dysfunctions (of this or other kind), rather than Ig gene deletions, may be the molecular basis of certain IgG2 deficiencies. To rule out a concomitant gross B cell dysfunction in these individuals, B lymphocyte phenotype and function were assayed in vitro, and found to be normal. A T cell line derived from one of the siblings displayed an abnormal TcR on the cell surface, but it showed several normal TcR-mediated functions. This suggests that the low number of peripheral T lymphocytes that have been found to express low TcR levels in these immunodeficiencies may be operational, and supplying sufficient “help” for the observed normal antibody responses to all tested protein, but not polysaccharide, antigens.
Human Genetics, 1991
A diallelic restriction fragment length polymorphism of the CD3-epsilon (ɛ) gene, which encodes f... more A diallelic restriction fragment length polymorphism of the CD3-epsilon (ɛ) gene, which encodes for an invariant component of the human T-lymphocyte receptor, is observed when using genomic DNA TaqI digests probed with a CD3-ɛ chain cDNA probe. This combination shows two alleles of 9.1 kb and 8.4 kb with a frequency of 0.66 and 0.34, respectively, in the Spanish population. None of these alleles is associated with susceptibility to juvenile rheumatoid arthritis (JRA) or insulin-dependent diabetes mellitus (IDDM).
Immunobiology of HLA, 1989
Human Immunology, 2008
The purpose of this study was to examine the expression of human leukocyte antigen-G (HLA-G) in p... more The purpose of this study was to examine the expression of human leukocyte antigen-G (HLA-G) in patients with systemic lupus erythematosus (SLE) and its relation with interleukin-10 (IL-10) production. The study included 50 female SLE patients and 59 healthy female donors. HLA-G expression in peripheral blood and cutaneous biopsies was determined by flow cytometry and immunohistochemistry, respectively. Soluble HLA-G (sHLA-G) and IL-10 were quantified in serum samples by enzyme-linked immunosorbent assay. SLE patients presented with serum sHLA-G and IL-10 levels significantly higher than that observed in controls (median [interquartile range (IQR)] = 43.6 U/ml [23.2–150.2] vs 26.84 U/ml [6.0–45.2], p = 0.004; and 1.4 pg/ml [0–2.3] vs 0 pg/ml [0–1.5], p = 0.01, respectively). But no correlation was observed between sHLA-G and both IL-10 levels and the disease activity index for SLE patients. The expression of membrane HLA-G in peripheral lymphocytes from SLE patients was low, but higher than in controls (median [IQR] = 1.5% [0.6–1.8] and 0.3% [0.2–0.8], respectively; p = 0.02). Finally, these findings were in accordance with the weak expression of HLA-G in skin biopsies. Despite the fact that patients present higher levels of HLA-G than healthy controls, which suggests a possible relevance of this molecule in SLE, it seems not to be related to IL-10 production or disease activity.
Scandinavian Journal of Immunology, 1992
The recent description of a selective human CD3γ deficiency and other T-cell receptor (TCR)/CD3 s... more The recent description of a selective human CD3γ deficiency and other T-cell receptor (TCR)/CD3 structural and functional defects, together with previous biochemical data on the structure and interactions of the TCR/CD3 complex, may aid in elucidating the physiology of this multi-subunit membrane ensemble. CD3γ seemed to be required for the commitment and thymic maturation of an important fraction of T lymphocytes to the CD8 (but not CD4) lineage, perhaps by participating with the CD8 co-receptor in the instructive signal delivered throtigh the αβ TCR during intrathymic positive selection by HLA class I molecules. The homologous CD3δ component would, in contrast, be necessary for the selection of CD4 lymphocytes by HLA class II molecules. The interaction of CD4 and CD8 with the TCR/CD3 complex during antigen recognition may thus be asymmetrical, taking place through CD3δ and γ respectively. Also, the existence of in vivo functional TCR/CD3 hemireceptors (lacking either CD3γ or CD3δ is suggested, and defects in their relative amount on the T-cell surface may disrupt unresponsiveness to self antigens and generate autoimmunity.
Leukemia & lymphoma, 2007
CD5 is a transmembrane protein expressed on all T lineage cells and a subset of B cells. It is kn... more CD5 is a transmembrane protein expressed on all T lineage cells and a subset of B cells. It is known that CD5 is physically associated with the T-cell receptor and B-cell receptor (BCR), inhibiting the signaling triggered by both of them. CD5 is also characteristic of B-chronic lymphocytic leukemia (B-CLL) B cells, although its implication in the development of this lymphoproliferative disorder has not been studied. In the present study, we examined the effect of CD5 in apoptosis, cell viability and global protein tyrosine phosphorylation mediated by BCR in B cells from B-CLL patients. As opposed to tonsil B cells, we did not observe an increase in the apoptotic or viability signals induced by anti-immunoglobulin M or SAC/ interleukin-2 when CD5 was dissociated from BCR in leukemic cells of the majority of patients. We also observed that CD5 did not regulate the BCR-induced phosphotyrosine pattern in B-CLL B cells. These findings suggest that CD5 does not inhibit properly the BCR-mediated signaling in leukemic cells. This defect in inhibiting the BCR might contribute to the enhanced survival of B-CLL B cells.
European Journal of Immunology, 1991
... Elisabeth AM Sanders, Ger T. Rijkers, Arjan W. Griffioen, Wietse Kuis, Ben JM Zegers ... Edit... more ... Elisabeth AM Sanders, Ger T. Rijkers, Arjan W. Griffioen, Wietse Kuis, Ben JM Zegers ... Editor-in-Chief: Dr. B. Kickhofen, Stiibeweg 51, D-7800 Freiburg, Federal Republic of ... Publishers: VCH Verlagsgesellschaft mbH (Managing Director: Hans Dirk Kiihler), Pappelallee 3, D-6940 ...
Scandinavian Journal of Immunology, 1992
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Papers by Paloma Perez-Aciego