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Patrick Blanco

Publications and source records attributed to Patrick Blanco.

17 recordsLinked to original sources
PubMed2006

Decrease in circulating dendritic cells predicts fatal outcome in septic shock.

OBJECTIVE: Biomarkers allowing accurate early staging of septic shock patients are lacking despite their obvious interest for patient management. Experimental models of septic shock in mouse previously noted a decrease in dendritic cell numbers. The aim of the study was to find a rapid reproducible biological test for an assessment of disease severity. DESIGN: Evaluation of peripheral blood dendritic cell counts by flow cytometry using three commercially available kits. PATIENTS AND PARTICIPANTS: Forty-two consecutive septic shock patients were studied prospectively. MEASUREMENTS AND RESULTS: Early low dendritic cell counts were correlated to disease severity as assessed by Simplified Acute Physiology Score or Sequential Organ Failure Assessment and predicted fatal outcome. The correlation was still present when the results were adjusted for age. CONCLUSION: The monitoring of blood dendritic cell count may provide an early and valuable assessment of the severity of the host response against infection and may influence the therapeutic management of septic shock patients.

Adult↗
PubMed2006

CD8+HLA-DR+ T lymphocytes are increased in common variable immunodeficiency patients with impaired memory B-cell differentiation.

The recently proposed Piqueras classification of common variable immunodeficiency (CVID) patients is based on flow cytometric quantification of IgD class-switched and CD27 membrane-expressing mature blood B cells. But, many patients also have circulating T cells with immunophenotypic abnormalities, often associated with clinical complications, such as splenomegaly, autoimmune disease, lymphoid proliferation and/or granulomatosis. In 50 unselected CIVD patients, classified according to CD27 and IgD B-cell expression, we analyzed T-lymphocyte subsets according to their expression of HLA-DR and intracellular perforin and/or granzyme B in CD8+ T lymphocytes, CCR7 and CD45RA. CD3+DR+ T-lymphocyte percentages, predominantly CD8+DR+, were significantly higher in patients with clinical complications. MB0 classified patients, characterized by fewer CD27+ B cells, had higher percentages of CD8+DR+ T lymphocytes expressing perforin and/or granzyme with a differentiated effector (CCR7- and CD45RA+) phenotype. In contrast, MB2 patients (with normal CD27+ and IgD- B cells) were free of clinical complications and showed no signs of T-cell activation. MB1 patients (normal CD27+ numbers but fewer IgD- B cells) were either clinically normal or had complications. Combining the set of markers described herein might better define homogeneous groups of patients for etiological studies and clearly segregate patients with clinical complications.

Adolescent↗
PubMed2006

Change in T-lymphocyte count after initiation of highly active antiretroviral therapy in HIV-infected patients with history of Mycobacterium avium complex infection.

OBJECTIVE: To compare changes in CD4+, CD8+ and total lymphocyte counts after initiation of highly active antiretroviral therapy (HAART) between HIV-infected patients with and without a recent history of Mycobacterium avium complex (MAC) infection. METHOD: Matched exposed-non-exposed retrospective cohort study. RESULTS: Fifty-one patients with a recent history of MAC infection (MAC+) started a combination of at least three antiretroviral drugs. They were individually matched to 145 patients without any history of MAC infection (MAC-) according to CD4+ T-cell count (+/- 30 cells/mm3), previous experience of antiretroviral treatment, AIDS clinical stage at the time of HAART initiation (baseline), age (+/- 10 years) and gender. MAC+ and MAC- patients presented comparable median levels of total lymphocytes (488 vs 688/mm3, P=0.09), CD4+ (11 vs 16/mm3, P=0.15), CD8+ count (359 vs 386/mm3, P=0.39) and plasma HIV RNA (5.3 vs 5.1 log10 copies/ml, P=0.22) at baseline. After 6 months on HAART, the median increase of CD4+ T-cell count was 28 cells/mm3 (interquartile range [IQR]: 1-63) in MAC+ and 72 cells/mm3 (IQR: 34-120) in MAC- patients (P<0.0001), whereas the percentage of CD4+ T cells was not significantly different between the two groups (P=0.13). Comparable differences were observed for total lymphocytes and CD8+ T cells (P<0.001). The 6 months decline of plasma HIV RNA was not significantly different according to MAC exposure (-1.6 in MAC+ vs -1.8 log10 copies/ml in MAC- patients, P=0.65). Results were confirmed after adjustment for other characteristics than the matching variables and after taking into account potential informative bias due to unbalanced number of deaths between the two groups. CONCLUSION: MAC infection at the time of HAART initiation is an important deleterious factor for immune reconstitution. A better understanding of the underlying mechanism and an evaluation of additional treatment strategies are necessary to help immune restoration in such circumstances.

AIDS-Related Opportunistic Infections↗
PubMed2005

Altered dendritic cell distribution in patients with common variable immunodeficiency.

Recent data suggest a critical role for dendritic cells (DCs) in the generation of immunoglobulin-secreting plasma cells. In the work reported herein, we analyzed the frequency of peripheral blood plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) in a cohort of 44 adults with common variable immunodeficiency (CVID) classified according to their CD27 membrane expression status on B cells. A deep alteration in the distribution of DC subsets, especially of pDCs, in the peripheral blood of CVID patients was found. Patients with a reduced number of class-switched CD27+IgD-IgM- memory B cells and patients with granulomatous disease had a dramatic decrease in pDCs (P = 0.00005 and 0.0003 vs controls, respectively) and, to a lesser extent, of mDCs (P = 0.001 and 0.01 vs controls, respectively). In contrast, patients with normal numbers of switched memory B cells had a DC distribution pattern similar to that in controls. Taken together, our results raise the possibility that innate immunity contributes to pathogenesis in CVID.

Adolescent↗
PubMed2005

Immunological markers after long-term treatment interruption in chronically HIV-1 infected patients with CD4 cell count above 400 x 10(6) cells/l.

OBJECTIVE: To analyse immunological markers associated with CD4+ lymphocyte T-cell count (CD4+) evolution during 12-month follow-up after treatment discontinuation. METHOD: Prospective observational study of chronically HIV-1 infected patients with CD4+ above 400 x 10(6) cells/l. RESULTS: CD4+ changes took place in two phases: an initial rapid decrease in the first month (-142 x 10(6) cells/l on average), followed by a slow decline (-17 x 10(6) cells/l on average) The second slope of CD4+ decline was not correlated with the first and only baseline plasma HIV RNA was associated with it. The decline in CD4+ during the first month was steeper in patients with higher CD4+ and weaker plasma HIV RNA baseline levels. Moreover, the decline was less pronounced (P < 10(-4)) in patients with CD4+ nadir above 350 x 10(6) cells/l (-65 x 10(6) cells/l per month) in comparison with those below 350 x 10(6) cells/l (-200 x 10(6) cells/l per month). A high number of dendritic cells (DCs) whatever the type was associated with high CD4+ at the time of treatment interruption and its steeper decline over the first month. Moreover, the myeloid DC level was stable whereas the lymphoid DC count, which tended to decrease in association with decrease in CD4+, was negatively correlated with the HIV RNA load slope. CONCLUSIONS: The results support the use of the CD4+ nadir to predict the CD4+ dynamic after treatment interruption and consideration of the CD4+ count after 1-month of interruption merely reflects the 12-month level of CD4+. Although DCs seem to be associated with the CD4+ dynamic, the benefit of monitoring them has still to be defined.

Adult↗
PubMed2005

Increase in activated CD8+ T lymphocytes expressing perforin and granzyme B correlates with disease activity in patients with systemic lupus erythematosus.

OBJECTIVE: Cytotoxic T lymphocyte-mediated killing using granzyme B has recently been proposed to be a preferential and selective source of autoantigens in systemic autoimmune diseases, including systemic lupus erythematosus (SLE), while other reports have indicated that cytolytic activity in SLE patients was decreased. The aim of this study was to examine the phenotypic and functional status of the CD8+ T cells in SLE patients. METHODS: Phenotype analysis of CD8+ T cells was carried out using flow cytometry. The cytotoxic potential of CD8+ T cells and its consequences were examined in redirected-killing experiments. SLE patients with quiescent disease (n = 41) were compared with SLE patients with active disease (n = 20), normal individuals (n = 36), and control patients with vasculitis (n = 14). Cytotoxic CD8+ T cell differentiation was examined by coculture with differentiated dendritic cells (DCs) in the presence of SLE patient sera. RESULTS: Patients with disease flares were characterized by higher proportions of perforin- and/or granzyme B-positive lymphocytes with a differentiated effector phenotype (CCR7- and CD45RA+). The frequency of these cells in peripheral blood correlated with clinical disease activity as assessed by the SLE Disease Activity Index. These cells generated high amounts of soluble nucleosomes as well as granzyme B-dependent unique autoantigen fragments. Finally, the activation of DCs with serum from a patient with active lupus induced granzyme B expression in CD8+ T lymphocytes. CONCLUSION: DCs generated in the presence of sera from SLE patients with active disease could promote the differentiation of CD8+ effector T lymphocytes that are fully functional and able to generate SLE autoantigens. Our data disclose a new and pivotal role of activated CD8+ T lymphocytes in SLE pathogenesis.

Adolescent↗
PubMed2005

Can highly active antiretroviral therapy be interrupted in patients with sustained moderate HIV RNA and > 400 CD4+ cells/microl? Impact on immunovirological parameters.

Because the effects of treatment interruption on patients with >400 CD4(+) cells/microl and prolonged moderate HIV loads is unknown, their HIV1 RNA and DNA loads, plasma, and PBMC resistance mutations and CD4+ kinetics were studied during 12 months of treatment interruption. Fifty-seven patients were included: 28 with undetectable (median 40 months) and 29 with moderate (>1 year) HIV1 RNA levels (3.3 log10 copies/ml) at the baseline M0. HIV1 RNA and CD4+ counts were determined monthly. PBMC HIV1 DNA was quantified (real-time PCR) and its reverse transcriptase (RT) and protease (PR) genotypes analyzed (M0, M6, M12). Regardless of HIV1 RNA detectability at the baseline M0, all patients had comparable HIV1 RNA (median 4.6), DNA (median 2.9), CD4+ (median 455) at month 12 (M12). The decisive moment was month 1 (M1), when the HIV1 RNA increase and CD4 decline stabilized, rendering M0 differences non-significant and predicting outcome. The lower the CD4+ nadir was before HAART, the steeper the CD4+ decline at M1. HIV1 DNA shifted to wild-type genotype in 47% (M6) and 79% (M12) of RT; 64% of PR major resistance mutations disappeared (M12). Treatment interruption is possible, regardless of the baseline M0 HIV RNA status, but it must take into consideration the CD4+ nadir, an outcome predictor, to initiate HAART before too severe depletion to preserve the possibility of treatment interruption. HIV1 DNA genotyping helps monitor patients with undetectable HIV RNA at M0.

Anti-HIV Agents↗
PubMed2005

Cytotoxic T lymphocytes and autoimmunity.

PURPOSE OF REVIEW: The possibility of the recognition by cytotoxic T lymphocytes of tissue autoantigens has been largely ignored in explaining organ-specific autoimmune diseases. Recent advances in the understanding of human leukocyte antigen class I-binding peptides motifs have led to the detection and the characterization of those autoreactive CD8(+) cytotoxic T lymphocytes involved in organ-specific autoimmune diseases. The purpose of this review is to discuss recent studies that shed light on the implication of cytotoxic T lymphocytes in several autoimmune disorders as well as the mechanisms underlying their stimulation. RECENT FINDINGS: Significant progress has been made in the characterization of autoantigens targeted by cytotoxic T lymphocytes in several class I-restricted autoimmune diseases, including Behçet's disease and ankylosing spondylitis, and their implication in systemic autoimmune disease such as systemic lupus erythematosus. Moreover, the signals involved in the activation of autoreactive cytotoxic T lymphocytes have been better characterized, particularly the molecular requirements of the antigen presentation at the surface of the dendritic cell system, mainly because of a better understanding of the Toll-like receptor-induced signals or the discovery of a defect in regulatory T cells. SUMMARY: New findings in the pathophysiology of cytotoxic T lymphocytes in autoimmunity and especially a better comprehension of their activation may give a new impetus for the development of targeted immunologic therapies in various autoimmune disorders.

Animals↗
PubMed2005

Activation of mesangial cells by platelets in systemic lupus erythematosus via a CD154-dependent induction of CD40.

BACKGROUND: Platelets are potential contributors to glomerular injury via the release of chemotactic and/or mitogenic mediators upon activation or through direct CD154/CD40-dependent interaction with cell components of the glomerulus. We examined whether platelets could activate mesangial cells and the potential role of the platelet-associated CD154. METHODS: Thrombin-activated platelets from systemic lupus erythematosus (SLE) patients or from disease or healthy controls were grown with human mesangial cells in the presence or not of a neutralizing anti-CD154 antibody either in contact or in a noncontact setting, the platelets and mesangial cells being separated by a pore size semipermeable membrane. The induction of mesangial cell surface antigens was assayed by flow cytometry. The quantification of mesangial cell proliferation was performed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and the production of transforming growth factor-beta1 (TGF-beta1), platelet-derived growth factor (PDGF) and soluble CD40 were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Activated platelets from patients with SLE could induce an up-regulation of the expression of CD40 on mesangial cells with a concomitant release of soluble CD40. This induction required a direct contact between platelets and mesangial cells and was dependent upon the platelet-associated CD154. Pathologic consequences of the up-regulation of CD40 were a CD40-dependent stimulation of the proliferation of mesangial cells and a CD40-dependent increased production of TGF-beta1 by these cells. CONCLUSION: Platelets from patients with SLE can activate mesangial cells through CD40/CD154 interactions, leading to an induction of proliferation of the mesangial cells and an enhanced production of TGF-beta1, a profibrotic cytokine.

Adult↗
PubMed2004

Platelet-associated CD154 in immune thrombocytopenic purpura.

CD40-ligand (CD154) is expressed on activated CD4+ T lymphocytes and is essential for the T cell-dependent activation of B lymphocytes. CD154 is also expressed at the activated platelet surface. In this study, we show that platelet-associated CD154 is increased in immune thrombocytopenic purpura (ITP), a disease characterized by an autoimmune response against proteins of the platelet membrane. CD154 and its messenger RNA were also present in increased amounts in the megakaryocytes of patients with ITP. We found that platelet-associated CD154 is competent to induce the CD40-dependent proliferation of B lymphocytes, and we observed an in vitro CD154-dependent production of antibodies to the GPIIb/IIIa complex (integrin alphaIIbbeta3) when platelets and peripheral blood B lymphocytes from ITP patients with circulating anti-GPIIb/IIIa antibody were cultured together. Therefore, platelet-associated CD154 expression is increased in ITP and is able to drive the activation of autoreactive B lymphocytes in this disease.

B-Lymphocytes↗
PubMed2004

Comparative analysis of NK cell subset distribution in normal and lymphoproliferative disease of granular lymphocyte conditions.

We have characterized the heterogeneity of human blood NK cell subsets defined by expression of KIR, lectin like receptors and NK cell differentiation markers within a cohort of 51 healthy Caucasian individuals. High inter-individual variability in cell surface expression of most NK cell markers is observed. Range values defining NK cell subsets in healthy donors were further used as references to characterize 14 patients with NK-type lymphoproliferative disease of granular lymphocytes (NK-LDGL). Alterations of the KIR repertoire were noted in all NK-LDGL patients. NK cell expansions were classified as oligoclonal KIR(+) or as non-detectable KIR ((nd)KIR) using anti-KIR2DL1/2DS1, anti-KIR2DL2/2DL3/2DS2, anti-KIR3DL1 and anti-KIR2DS4 monoclonal antibodies. A major reduction in the size of the CD56(bright) NK cell subset was a constant feature of NK-LDGL. Altered distribution of CD94(+), CD161(+), and CD162R(+) NK cell subsets was also observed in NK-LDGL patients. Considering the potential role of NK cells in eliminating tumors or virus-infected cells, the reference values defined in this study should be valuable to characterize both quantitative and qualitative alterations of the NK cell repertoire in pathological conditions and to monitor NK cell reconstitution following hematopoietic transplantation.

Adolescent↗
PubMed2003

Dendritic cells: controllers of the immune system and a new promise for immunotherapy.

The immune system is controlled by dendritic cells (DCs). Just as lymphocytes comprise different subsets, DCs comprise several subsets that differentially control lymphocyte function. In humans, the myeloid pathway includes Langerhans cells (LCs) and interstitial DCs (intDCs). While both subsets produce IL-12, only intDCs make IL-10 and induce B cell differentiation. Another pathway includes plasmacytoid DCs, which promptly secrete large amounts of IFN-alpha/beta viral encounter. Thus, insights into in vivo DC functions are important to understand the launching and modulation of immunity.

Dendritic Cells↗
PubMed2003

[Celiac disease and autoimmune diseases or systemic disease. Six cases and a review of the literature].

BACKGROUND: Celiac disease is an autoimmune disorder which may be associated with another autoimmune or systemic disease. OBJECTIVE: To determine the links between autoimmune diseases and celiac disease. PATIENTS AND METHODS: Among 31 patients with a celiac disease, we selected those who had another autoimmune or systemic disease. RESULTS: We report 6 patients with such disease association: 3 with autoimmune thyroiditis including one also with Grave's disease, 2 with systemic lupus erythematosus including one also with insulin-dependent diabetes mellitus, and 1 with temporal arteritis. CONCLUSION: The link between celiac disease and autoimmune thyroiditis or insulin-dependent diabetes mellitus seems to be real but many discrepancies are observed for the other autoimmune diseases. After a literature review, we suggest a summary of effective associations between celiac disease and autoimmune or systemic diseases.

Adolescent↗
PubMed2002

Blood dendritic cells and DC-poietins in systemic lupus erythematosus.

Dendritic cells (DCs) control immunity and tolerance. Hence, we surmised that systemic lupus erythematosus (SLE), a systemic autoimmune disease with autoreactive T and B cells, might be due to alterations in DC homeostasis. Taken together, our results demonstrate profound alterations of DCs and DC-poietins homeostasis in SLE. Elevated levels of interferon-alpha (IFN) in serum of SLE patients coexist with decreased numbers of cells producing IFN-alpha, i.e., plasmacytoid dendritic cells (PDCs). Decreased numbers of circulating DCs correlate with increased levels of soluble tumor necrosis factor (TNF) receptors, thus suggesting the potential role of TNF pathway in the observed DC alterations. Finally, increased FMS-like tyrosine kinase 3-ligand (FLT3-L) and its correlation with soluble TNF receptors suggest a physiologic response to compensate low DC numbers. Although IFN-alpha remains at the center of immunologic aberrations in SLE, it remains to be determined whether increased shedding of soluble TNF receptors could also be ascribed to IFN-alpha.

Adolescent↗
PubMed2002

The interplay of dendritic cell subsets in systemic lupus erythematosus.

Dendritic cells (DC) control immunity and tolerance. Hence, we surmised that systemic lupus erythematosus (SLE), a systemic autoimmune disease with autoreactive T and B cells, might be due to DC alterations. Based on our findings, we are proposing a model of SLE where autoimmune responses are driven by unabated activation of myeloid DC through IFN-alpha produced by plasmacytoid DC. Thus, interplay between DC subsets might represent a key component of SLE pathogenesis.

Autoantibodies↗