49 results on '"Caragol, I"'
Search Results
2. Kinase mutant Btk results in atypical X-linked agammaglobulinaemia phenotype
- Author
-
GASPAR, H. B., FERRANDO, M., CARAGOL, I., HERNANDEZ, M., BERTRAN, J. M., DE GRACIA, X., LESTER, T., KINNON, C., ASHTON, E., and ESPANOL, T.
- Published
- 2000
3. A novel CD18 genomic deletion in a patient with severe leucocyte adhesion deficiency: a possible CD2/lymphocyte function-associated antigen-1 functional association in humans
- Author
-
ALLENDE, L. M., HERNÁNDEZ, M., CORELL, A., GARCÍA-PÉREZ, M. A., VARELA, P., MORENO, A., CARAGOL, I., GARCÍA-MARTÍN, F., GUILLÉN-PERALES, J., OLIVÉ, T., ESPAÑOL, T., and ARNAIZ-VILLENA, A.
- Published
- 2000
4. Circumscribed scleroderma in congenital rubella syndrome with hypogammaglobulinemia
- Author
-
Español, T., Pascual, C., Huguet, P., Caragol, I., Hernandez, M., and Bertran, J. M.
- Published
- 1998
5. Vertical HIV-1 transmission correlates with a high maternal viral load at delivery
- Author
-
Coll, O., Hernandez, M., Boucher, C.A.B., Fortuny, C., De Tejada, B.M., Canet, Y., Caragol, I., Tijnagel, J., Bertran, J.M., and Espanol, T.
- Subjects
HIV infection in pregnancy ,Viremia -- Measurement ,HIV (Viruses) -- Measurement ,Health - Abstract
High blood levels of HIV-1 in pregnant women at delivery appears to be the greatest risk factor for transmitting the virus to the newborn infant. Researchers took blood samples taken from 67 pregnant women at delivery and tested the samples for HIV-1 RNA and the viral antigen p24. The 69 infants were followed up to the age of 18 months. The transmission rate in the group was 25%. Women with high viral RNA counts and low CD4 counts were more likely to transmit the virus. High viral counts are probably the most important risk factor, since zidovudine can reduce the transmission rate.
- Published
- 1997
6. Postnatal Transmission of HIV Infection
- Author
-
Español, T., Caragol, I., and Bertrán, J. M.
- Published
- 1992
- Full Text
- View/download PDF
7. The European internet-based patient and research database for primary immunodeficiencies: results 2006-2008
- Author
-
Gathmann B., Grimbacher B., Beauté J., Dudoit Y., Mahlaoui N., Fischer A., Knerr V., Kindle G., Micol R., Benslama L., Plebani A., Notarangelo L., PIGNATA, CLAUDIO, Bangs C., Lucas M., Tierney P., Core C., Dempster J., Exley A., Kumararatne D., Paschenko O., Kondratenko I., Shcherbina A., Velbri S., Ciznar P., Duobiene R., Kilic S., Kütükcüler N., Sanal O., Reisli I., Yegin O., Kanariou M., Papadopoulou Alataki E., Trachana M., Hatzistilianou M., Farber C.M., Meyts I., Pasic S., Richter D., Marodi L., Touitou I., Abuzakouk M., Feighery C., Thon V., Litzman J., Cucuruz M., Wolska B., Szaflarska A., Reda S., Soler P., Caragol I., Llobet P., Savchak I., Marques L., Koren A., Hörnes M., Shchebet S., Goldacker S., Ritterbusch H., Fasshauer M., Sollinger F., Witte T., Baumann U., Wittkowski H., Viemann D., Niehues T., Stimm H., Brodszki N., Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Gathmann, B., Grimbacher, B., Beauté, J., Dudoit, Y., Mahlaoui, N., Fischer, A., Knerr, V., Kindle, G., Micol, R., Benslama, L., Plebani, A., Notarangelo, L., Pignata, Claudio, Bangs, C., Lucas, M., Tierney, P., Core, C., Dempster, J., Exley, A., Kumararatne, D., Paschenko, O., Kondratenko, I., Shcherbina, A., Velbri, S., Ciznar, P., Duobiene, R., Kilic, S., Kütükcüler, N., Sanal, O., Reisli, I., Yegin, O., Kanariou, M., Papadopoulou Alataki, E., Trachana, M., Hatzistilianou, M., Farber, C. M., Meyts, I., Pasic, S., Richter, D., Marodi, L., Touitou, I., Abuzakouk, M., Feighery, C., Thon, V., Litzman, J., Cucuruz, M., Wolska, B., Szaflarska, A., Reda, S., Soler, P., Caragol, I., Llobet, P., Savchak, I., Marques, L., Koren, A., Hörnes, M., Shchebet, S., Goldacker, S., Ritterbusch, H., Fasshauer, M., Sollinger, F., Witte, T., Baumann, U., Wittkowski, H., Viemann, D., Niehues, T., Stimm, H., and Brodszki, N.
- Subjects
Male ,Databases, Factual ,Quality Assurance, Health Care ,International Cooperation ,PID controller ,registry ,0302 clinical medicine ,Epidemiology ,Prevalence ,Immunology and Allergy ,Data Protection Act 1998 ,Registries ,Child ,ComputingMilieux_MISCELLANEOUS ,Password ,ESID ,0303 health sciences ,Immunoglobulins, Intravenous ,Middle Aged ,3. Good health ,Europe ,Identification (information) ,Child, Preschool ,Female ,The Internet ,epidemiology ,Adult ,medicine.medical_specialty ,Adolescent ,Immunology ,online database ,primary immunodeficiency ,Young Adult ,03 medical and health sciences ,medicine ,Humans ,Aged ,030304 developmental biology ,Internet ,business.industry ,Immunologic Deficiency Syndromes ,Infant, Newborn ,Online database ,Infant ,Original Articles ,medicine.disease ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Primary immunodeficiency ,business ,030215 immunology - Abstract
Summary Primary immunodeficiencies (PID) are rare diseases; therefore transnational studies are essential to maximize the scientific outcome and to improve diagnosis and therapy. In order to estimate the prevalence of PID in Europe as well as to establish and evaluate harmonized guidelines for the diagnosis and treatment of PID, the European Society for Immunodeficiencies (ESID) has developed an internet-based database for clinical and research data on patients with PID. This database is a platform for epidemiological analyses as well as the development of new diagnostic and therapeutic strategies and the identification of novel disease-associated genes. Within 4 years, 7430 patients from 39 countries have been documented in the ESID database. Common variable immunodeficiency (CVID) represents the most common entity, with 1540 patients or 20·7% of all entries, followed by isolated immunoglobulin (Ig)G subclass deficiency (546 patients, 7·4%). Evaluations show that the average life expectancy for PID patients varies from 1 to 49 years (median), depending on the type of PID. The prevalence and incidence of PID remains a key question to be answered. As the registration progress is far from finished we can only calculate minimum values for PID, with e.g. France currently showing a minimum prevalence of 3·72 patients per 100 000 inhabitants. The most frequently documented permanent treatment is immunoglobulin replacement; 2819 patients (42% of all patients alive) currently receive this form of treatment.
- Published
- 2009
8. Experience with basiliximab in pediatric renal transplantation
- Author
-
Vilalta, R, Vila, A, Nieto, J, Espan̄ol, T, Caragol, I, and Callı́s, L
- Published
- 2002
- Full Text
- View/download PDF
9. Low penetrance, broad resistance, and favorable outcome of interleukin 12 receptor beta 1 deficiency: Medical and immunological implications
- Author
-
Fieschi, C, Dupuis, S, Catherinot, E, Feinberg, J, Bustamante, J, Breiman, A, Altare, F, Baretto, R, Le Deist, F, Kayal, S, Koch, H, Richter, D, Brezina, M, Aksu, G, Wood, P, Al-Jumaah, S, Raspall, M, Duarte, AJD, Tuerlinckx, D, Virelizier, JL, Fischer, A, Enright, A, Bernhoft, J, Cleary, AM, Vermylen, C, Rodriguez-Gallego, C, Davies, G, Blutters-Sawatzki, R, Siegrist, CA, Ehlayel, MS, Novelli, V, Haas, WH, Levy, J, Freihorst, J, Al-Hajar, S, Nadal, D, Vasconcelos, DD, Jeppsson, O, Kutukculer, N, Frecerova, K, Caragol, I, Lammas, D, Kumararatne, DS, Abel, L, Casanova, JL, and Ege Üniversitesi
- Subjects
interferon gamma ,Salmonella ,Mycobacteria ,immunodeficiency ,interleukin 12 receptor - Abstract
WOS: 000181179400012, PubMed ID: 12591909, The clinical phenotype of interleukin 12 receptor beta1 chain (IL-12Rbeta1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rbeta1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guerin -BCG- and environmental Mycobacteria). Three patients had clinical tuberculosis, one of whom also had salmonellosis. Unlike salmonellosis, mycobacterial infections did not recur. BCG inoculation and BCG disease were both effective against subsequent environmental mycobacteriosis, but not against salmonellosis. Excluding the probands, seven of the 12 affected siblings have remained free of case-definition opportunistic infection. Finally, only five deaths occurred in childhood, and the remaining 36 patients are alive and well. Thus, a diagnosis of IL-12Rbeta1 deficiency should be considered in children with opportunistic mycobacteriosis or salmonellosis; healthy siblings of probands and selected cases of tuberculosis should also be investigated. The overall prognosis is good due to broad resistance to infection and the low penetrance and favorable outcome of infections. Unexpectedly, human IL-12 is redundant in protective immunity against most microorganisms other than Mycobacteria and Salmonella. Moreover, IL-12 is redundant for primary immunity to Mycobacteria and Salmonella in many individuals and for secondary immunity to Mycobacteria but not to Salmonella in most.
- Published
- 2003
10. Low penetrance, broad resistance, and favorable outcome of interleukin 12 receptor ß1 deficiency: Medical and immunological implications
- Author
-
Fieschi C., Dupuis S., Catherinot E., Feinberg J., Bustamante J., Breiman A., Altare F., Baretto R., Le Deist F., Kayal S., Koch H., Richter D., Brezina M., Aksu G., Wood P., Al-Jumaah S., Raspall M., Da Silva Duarte A.J., Tuerlinckx D., Virelizier J.-L., Fischer A., Enright A., Bernhöft J., Cleary A.M., Vermylen C., Rodriguez-Gallego C., Davies G., Blütters-Sawatzki R., Siegrist C.-A., Ehlayel M.S., Novelli V., Haas W.H., Levy J., Freihorst J., Al-Hajjar S., Nadal D., De Moraes Vasconcelos D., Jeppsson O., Kutukculer N., Frecerova K., Caragol I., Lammas D., Kumararatne D.S., Abel L., Casanova J.-L., and Ege Üniversitesi
- Subjects
ComputingMilieux_MANAGEMENTOFCOMPUTINGANDINFORMATIONSYSTEMS ,ComputingMethodologies_PATTERNRECOGNITION ,Interferon ? ,MycobacteriaSalmonella ,ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS ,Immunodeficiency ,InformationSystems_MISCELLANEOUS ,Interleukin 12 receptor - Abstract
PubMed ID: 12591909, The clinical phenotype of interleukin 12 receptor ß1 chain (IL-12Rß1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rß1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guérin-BCG- and environmental Mycobacteria). Three patients had clinical tuberculosis, one of whom also had salmonellosis. Unlike salmonellosis, mycobacterial infections did not recur. BCG inoculation and BCG disease were both effective against subsequent environmental mycobacteriosis, but not against salmonellosis. Excluding the probands, seven of the 12 affected siblings have remained free of case-definition opportunistic infection. Finally, only five deaths occurred in childhood, and the remaining 36 patients are alive and well. Thus, a diagnosis of IL-12Rß1 deficiency should be considered in children with opportunistic mycobacteriosis or salmonellosis; healthy siblings of probands and selected cases of tuberculosis should also be investigated. The overall prognosis is good due to broad resistance to infection and the low penetrance and favorable outcome of infections. Unexpectedly, human IL-12 is redundant in protective immunity against most microorganisms other than Mycobacteria and Salmonella. Moreover, IL-12 is redundant for primary immunity to Mycobacteria and Salmonella in many individuals and for secondary immunity to Mycobacteria but not to Salmonella in most.
- Published
- 2003
11. A novel CD18 genomic deletion in a patient with severe leucocyte adhesion deficiency: a possible CD2/lymphocyte function-associated antigen-1 functional association in humans
- Author
-
Allende, L M, Hernández, M, Corell, A, García-Pérez, M A, Varela, P, Moreno, A, Caragol, I, García-Martín, F, Guillén-Perales, J, Olivé, T, Español, T, and Arnaiz-Villena, A
- Subjects
Male ,Cytoplasm ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,T-Lymphocytes ,Homozygote ,Leukocyte-Adhesion Deficiency Syndrome ,Molecular Sequence Data ,CD2 Antigens ,Infant ,Original Articles ,Flow Cytometry ,Lymphocyte Activation ,Lymphocyte Function-Associated Antigen-1 ,Herpesvirus 2, Saimiriine ,CD18 Antigens ,Humans ,Gene Deletion ,Cell Line, Transformed - Abstract
Leucocyte adhesion deficiency (LAD) is an autosomal-recessive genetic disease that is characterized clinically by severe bacterial infections and caused by mutations in the CD18 gene that codes for the beta2 integrin subunit. A patient with a severe LAD phenotype was studied and the molecular basis of the disease was identified as a single homozygous defect in a Herpes virus saimiri (HVS)-transformed T-cell line. The defect identified involves a deletion of 171 bp in the cDNA that encodes part of the proteic extracellular domain. This genetic abnormality was further studied at the genomic DNA level and found to consist of a deletion of 169 bp (from -37 of intron 4 to +132 of exon 5), which abolishes the normal splicing and results in the total skipping of exon 5. The 171-bp shortened 'in-frame' mRNA not only resulted in the absence of CD18 expression on the cell surface but also in its absence in the cytoplasm of HVS T-cell lines. Functionally, the LAD-derived HVS T-cell lines showed a severe, selective T-cell activation impairment in the CD2 (but not in the CD3) pathway. This defect was not reversible when exogenous interleukin-2 (IL-2) was added, suggesting that there is also a functional interaction of the lymphocyte function-associated antigen-1 (LFA-1) protein in the CD2 signal transduction pathway in human T cells, as has been previously reported in mice and in the human Papillon-Lefèvre syndrome. Thus, HVS transformation is not only a suitable model for T-cell immunodeficiency studies and characterization, but is also a good system for investigating the immune system in pathological conditions. It may also be used in the future in cellular models for in vitro gene-therapy trials.
- Published
- 2000
12. [Immunologic prognostic parameters in infection by the human immunodeficiency virus]
- Author
-
Máñez R, Caragol I, Esteban Ribera, Ocaña I, Español T, and Jm, Martínez Vázquez
- Subjects
Interferon-gamma ,Leukocyte Count ,Interferon Type I ,CD4-CD8 Ratio ,Humans ,HIV Infections ,Receptors, Interleukin-2 ,Phytohemagglutinins ,Pregnancy Proteins ,Prognosis - Abstract
To evaluate the use of quantitative and functional immunologic parameters as prognostic markers of infection by the human immunodeficiency virus (HIV).The number of CD4 and CD8 lymphocytes, the CD4/CD8 ratio, the percentage of interleukin 2 (IL-2) receptors, the response to phytohemaglutinin (PHA) and the production of interferon tau (IFN-tau), were analyzed in 85 patients with HIV infection: 14 with acquired immunodeficiency syndrome (AIDS) (stage IV), 16 with persistent generalized adenopathies (stage III), and 55 asymptomatic patients (stage II). Similarly, a control group of 35 blood donors with negative HIV serology was studied.Over a period of 30 months, 17 patients (5 of stage III and 12 of stage II) evolved to stage IV. In a multivariate analysis the decrease in the number of CD4 lymphocytes in stage II and the decrease in the production of IFN-tau in stage II and III were the parameters associated with progression to stage IV.The decrease in the production of interferon tau in patients with infection by the human immunodeficiency virus in stage II and III as well as the decrease in the number of CD4 lymphocytes in stage II are prognostic factors associated with the evolution to stage IV of the infection.
- Published
- 1992
13. Changes in peripheral blood lymphocyte patterns during early acute liver rejection: B cell increase as an index of rejection
- Author
-
Ramon Charco, Máñez R, Caragol I, Llopart L, Español T, and Margarit C
- Subjects
Graft Rejection ,B-Lymphocytes ,Antigens, CD ,T-Lymphocytes ,CD4 Antigens ,Antibodies, Monoclonal ,Humans ,Biomarkers ,Liver Transplantation - Published
- 1992
14. Clinical Tuberculosis in 2 of 3 Siblings with Interleukin-12 Receptor 1 Deficiency
- Author
-
Caragol, I., primary, Raspall, M., additional, Fieschi, C., additional, Feinberg, J., additional, Larrosa, M. N., additional, Hernandez, M., additional, Figueras, C., additional, Bertran, J.-M., additional, Casanova, J.-L., additional, and Espanol, T., additional
- Published
- 2003
- Full Text
- View/download PDF
15. Evaluation of the putative role of C-C chemokines as protective factors of HIV-1 infection in seronegative hemophiliacs exposed to contaminated hemoderivatives
- Author
-
Barretina, J., primary, Blanco, J., additional, Gutierrez, A., additional, Puig, L., additional, Altisent, C., additional, Espanol, T., additional, Caragol, I., additional, Clotet, B., additional, and Este, J.A., additional
- Published
- 2000
- Full Text
- View/download PDF
16. CD28 regulation in liver transplant recipients treated with two different immunosuppressive regimens
- Author
-
Charco, R, primary, Caragol, I, additional, Urbán, S, additional, Lázaro, J.L, additional, Murio, E, additional, Dávila, R, additional, and Margarit, C, additional
- Published
- 1999
- Full Text
- View/download PDF
17. CCR5 genotype and HIV-1 infection in perinatally-exposed infants
- Author
-
Mas, A., primary, Español, T., additional, Heredia, A., additional, Antonia Pedraza, M., additional, Hernandez, M., additional, Caragol, I., additional, Fernando, M., additional, Bertran, J.M., additional, Alcami, J., additional, and Soriano, V., additional
- Published
- 1999
- Full Text
- View/download PDF
18. Circumscribed scleroderma in congenital rubella syndrome with hypogammaglobulinemia
- Author
-
espaol, T., primary, Pascual, C., additional, Huguet, P., additional, Caragol, I., additional, Hernandez, M., additional, and Bertran, J. M., additional
- Published
- 1998
- Full Text
- View/download PDF
19. Development of a Common Variable Immunodeficiency in IgA-Deficient Patients
- Author
-
Español, T., primary, Catala, M., additional, Hernandez, M., additional, Caragol, I., additional, and Bertran, J.M., additional
- Published
- 1996
- Full Text
- View/download PDF
20. Very late presentation of vertically transmitted HIV‐1 infection
- Author
-
Español, T, primary, Figueras, MC, additional, Soriano, V, additional, Caragol, I, additional, Hernandez, M, additional, and Bertran, JM, additional
- Published
- 1996
- Full Text
- View/download PDF
21. Evolution of immunological abnormalities in HIV infection by vertical transmission
- Author
-
Español, T, primary, Caragol, I, additional, and Bertran, JM, additional
- Published
- 1994
- Full Text
- View/download PDF
22. Immunological Abnormalities in Pediatric Aids
- Author
-
Español, T., primary, Garcia, X., additional, Caragol, I., additional, Sauleda, S., additional, and Muntane, C., additional
- Published
- 1991
- Full Text
- View/download PDF
23. A randomized controlled trial of α-interferon in acute postransfusion C hepatitis
- Author
-
Viladomiu, L, primary, González, A, additional, López-Talavera, JC, additional, Genescá, J, additional, Allende, H, additional, Sánchez, C, additional, Hernández, JM, additional, Caragol, I, additional, Butt, M, additional, Esteban, JI, additional, Esteban, R, additional, and Guardia, J, additional
- Published
- 1990
- Full Text
- View/download PDF
24. DNA ploidy study of resected hepatocellular carcinoma in cirrhotic liver
- Author
-
Balsells, J., Caragol, I., Allende, E., Diaz, I., Charco, R., Lazaro, J.-L., Murio, E., and Margarit, C.
- Published
- 1996
- Full Text
- View/download PDF
25. Diagnosis of Chronic Granulomatous Disease (CGD) in Adults
- Author
-
Martín-Lázaro, J., Urban, S., García-Patos, V., Hernández, M., Español, T., and Caragol, I.
- Published
- 2006
- Full Text
- View/download PDF
26. CD40L expression in primary antibody immunodeficiencies,EXPRESION DE CD40L EN INMUNODEFICIENCIAS PRIMARIAS DE ANTICUERPOS
- Author
-
Hernandez Gonzalez, M., Caragol, I., Javier De Gracia, Ferrando, M., Urban, S., and Espanol, T.
27. Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells
- Author
-
de Beaucoudrey, L, Puel, A, Filipe-Santos, O, Cobat, A, Ghandil, P, Chrabieh, M, Feinberg, J, von Bernuth, H, Samarina, A, Jannière, L, Fieschi, C, Stéphan, J L, Boileau, C, Lyonnet, S, Jondeau, G, Cormier-Daire, V, Le Merrer, M, Hoarau, C, Lebranchu, Y, Lortholary, O, Chandesris, M O, Tron, F, Gambineri, E, Bianchi, L, Rodriguez-Gallego, C, Zitnik, S E, Vasconcelos, J, Guedes, M, Vitor, A B, Marodi, L, Chapel, H, Reid, B, Roifman, C, Nadal, D, Reichenbach, J, Caragol, I, Garty, B Z, Dogu, F, Camcioglu, Y, Gülle, S, Sanal, O, Fischer, A, Abel, L, Stockinger, B, Picard, C, and Casanova, J L
- Subjects
3. Good health
28. Efficacy of alfa-interferon to prevent chronicity in patients with acute postransfusion non-A non-B hepatitis: A randimized, controlled trial
- Author
-
Viladomiu, L, primary, Esteban, JI, additional, González, A, additional, Lavera, JC López-Ta, additional, Sánchez, C, additional, Quer, J, additional, Caragol, I, additional, Hernández, JH, additional, Esteban, R, additional, Guardia, J, additional, Kuo, G, additional, and Houghton, M, additional
- Published
- 1989
- Full Text
- View/download PDF
29. High-content cytometry and transcriptomic biomarker profiling of human B-cell activation
- Author
-
Christoph Klein, Karl Welte, László Maródi, Mareike Sass, Claudia Ilginus, Gesine Hansen, Anna Szaflarska, Ulrich Baumann, Julia Skokowa, Isabel Caragol, Christian Hennig, Claudio Pignata, Sara Sebnem Kilic, Kaan Boztug, Hennig, C., Ilginus, C., Boztug, K., Skokowa, J., Marodi, L., Szaflarska, A., Sass, M., Pignata, Claudio, Kilic, S. S., Caragol, I., Baumann, U., Klein, C., Welte, K., and Hansen, G.
- Subjects
Male ,Lymphocyte Activation ,Chemokine CXCL9 ,Transcriptome ,Activation-induced (cytidine) deaminase ,AID ,Immunology and Allergy ,CD40L ,Child ,Cells, Cultured ,Image Cytometry ,B-Lymphocytes ,Primary immunodeficiency ,CVID ,Cell Differentiation ,Cytidine deaminase ,Cell cycle ,Middle Aged ,Biomarker (medicine) ,Female ,CD40 ligand ,Primary antibody deficiency ,Activation-induced cytidine deaminase ,Adult ,Adolescent ,DNA repair ,Immunology ,Biology ,Common variable immunodeficiency ,Young Adult ,Magnetic-activated cell sorting ,medicine ,Humans ,RNA, Messenger ,CSR ,Microarray analysis techniques ,Chip cytometry ,Gene Expression Profiling ,PID ,Immunologic Deficiency Syndromes ,Infant, Newborn ,B-cell immunology ,medicine.disease ,Microarray Analysis ,Molecular biology ,Immunoglobulin Class Switching ,High-Throughput Screening Assays ,Chemokine CXCL10 ,Cancer research ,biology.protein ,MACS ,Class-switch recombination ,Biomarkers - Abstract
Background Primary antibody deficiencies represent the most prevalent, although very heterogeneous, group of inborn immunodeficiencies, with a puzzling complexity of cellular and molecular processes involved in disease pathogenesis. Objective We aimed to study in detail the kinetics of CD40 ligand/IL-21–induced B-cell differentiation to define new biomarker sets for further research into primary antibody deficiencies. Methods We applied high-content screening methods to monitor B-cell activation on the cellular (chip cytometry) and transcriptomic (RNA microarray) levels. Results The complete activation process, including stepwise changes in protein and RNA expression patterns, entry into the cell cycle, proliferation and expression of activation-induced cytidine deaminase (AID), DNA repair enzymes, and post–class-switch expression of IgA and IgG, was successfully monitored during in vitro differentiation. We identified a number of unknown pathways engaged during B-cell activation, such as CXCL9/CXCL10 secretion by B cells. Finally, we evaluated a deduced set of biomarkers on a group of 18 patients with putative or proved intrinsic B-cell defects recruited from the European Society for Immunodeficiencies database and successfully predicted 2 AID defects and 1 DNA repair defect. Complete absence of class-switched B cells was a sensitive predictor of AID deficiency and should be further evaluated as a diagnostic biomarker. Conclusion The biomarkers found in this study could be used to further study the complex process of B-cell activation and to understand conditions that lead to the development of primary antibody deficiencies.
- Published
- 2014
30. Apoptosis for prediction of radiotherapy late toxicity: lymphocyte subset sensitivity and potential effect of TP53 Arg72Pro polymorphism.
- Author
-
Fuentes-Raspall MJ, Caragol I, Alonso C, Ramón y Cajal T, Fisas D, Seoane A, Carvajal N, Bonache S, Díez O, and Gutiérrez-Enríquez S
- Subjects
- Adult, Apoptosis radiation effects, Breast Neoplasms genetics, Breast Neoplasms metabolism, Breast Neoplasms pathology, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes pathology, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes pathology, Case-Control Studies, Cells, Cultured, Female, Fibrosis, Gene Expression, Humans, Killer Cells, Natural immunology, Killer Cells, Natural pathology, Lymphocyte Subsets immunology, Lymphocyte Subsets pathology, Middle Aged, Prognosis, Prospective Studies, Radiation Tolerance, Telangiectasis genetics, Telangiectasis metabolism, Telangiectasis pathology, Treatment Outcome, Tumor Suppressor Protein p53 metabolism, Breast Neoplasms radiotherapy, CD4-Positive T-Lymphocytes radiation effects, CD8-Positive T-Lymphocytes radiation effects, Gamma Rays adverse effects, Killer Cells, Natural radiation effects, Lymphocyte Subsets radiation effects, Polymorphism, Genetic, Tumor Suppressor Protein p53 genetics
- Abstract
We tested apoptosis levels in in vitro irradiated T-lymphocytes from breast cancer (BC) patients with radiotherapy-induced late effects. Previous results reported in the literature were revised. We also examined the effect of TP53 Arg72Pro polymorphism on irradiation-induced apoptosis (IA). Twenty BC patients, ten with fibrosis and/or telangiectasias and ten matched controls with no late reactions, were selected from those receiving radiotherapy between 1993 and 2007. All patients were followed-up at least 6 years after radiotherapy. Using the combination of both CD3 and CD8 antibodies the in vitro IA was measured in CD3, CD8 and CD4 T-lymphocytes, and CD8 natural killer lymphocytes (CD8 NK) by flow cytometry. The TP53 Arg72Pro genotype was determined by sequencing. Patients with late radiotherapy toxicity showed less IA for all T-lymphocytes except for the CD8 NK. CD8 NK showed the highest spontaneous apoptosis and the lowest IA. IA in patients with toxicity appears to be lower than the control patients only in TP53 Arg/Arg patients (P = 0.077). This difference was not present in patients carrying at least one Pro allele (P = 0.8266). Our data indicate that late side effects induced by radiotherapy of BC are associated to low levels of IA. CD8 NK cells have a different response to in vitro irradiation compared to CD8 T-lymphocytes. It would be advisable to distinguish the CD8 NK lymphocytes from the pool of CD8+ lymphocytes in IA assays using CD8+ cells. Our data suggest that the 72Pro TP53 allele may influence the IA of patients with radiotherapy toxicity.
- Published
- 2015
- Full Text
- View/download PDF
31. High-content cytometry and transcriptomic biomarker profiling of human B-cell activation.
- Author
-
Hennig C, Ilginus C, Boztug K, Skokowa J, Marodi L, Szaflarska A, Sass M, Pignata C, Kilic SS, Caragol I, Baumann U, Klein C, Welte K, and Hansen G
- Subjects
- Adolescent, Adult, Biomarkers metabolism, Cell Differentiation, Cells, Cultured, Chemokine CXCL10 genetics, Chemokine CXCL10 metabolism, Chemokine CXCL9 genetics, Chemokine CXCL9 metabolism, Child, Female, Gene Expression Profiling, High-Throughput Screening Assays, Humans, Image Cytometry, Immunoglobulin Class Switching, Immunologic Deficiency Syndromes immunology, Infant, Newborn, Male, Microarray Analysis, Middle Aged, RNA, Messenger analysis, Transcriptome immunology, Young Adult, B-Lymphocytes immunology, Immunologic Deficiency Syndromes diagnosis, Lymphocyte Activation genetics
- Abstract
Background: Primary antibody deficiencies represent the most prevalent, although very heterogeneous, group of inborn immunodeficiencies, with a puzzling complexity of cellular and molecular processes involved in disease pathogenesis., Objective: We aimed to study in detail the kinetics of CD40 ligand/IL-21-induced B-cell differentiation to define new biomarker sets for further research into primary antibody deficiencies., Methods: We applied high-content screening methods to monitor B-cell activation on the cellular (chip cytometry) and transcriptomic (RNA microarray) levels., Results: The complete activation process, including stepwise changes in protein and RNA expression patterns, entry into the cell cycle, proliferation and expression of activation-induced cytidine deaminase (AID), DNA repair enzymes, and post-class-switch expression of IgA and IgG, was successfully monitored during in vitro differentiation. We identified a number of unknown pathways engaged during B-cell activation, such as CXCL9/CXCL10 secretion by B cells. Finally, we evaluated a deduced set of biomarkers on a group of 18 patients with putative or proved intrinsic B-cell defects recruited from the European Society for Immunodeficiencies database and successfully predicted 2 AID defects and 1 DNA repair defect. Complete absence of class-switched B cells was a sensitive predictor of AID deficiency and should be further evaluated as a diagnostic biomarker., Conclusion: The biomarkers found in this study could be used to further study the complex process of B-cell activation and to understand conditions that lead to the development of primary antibody deficiencies., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
32. Subjectivity and flow cytometric variability.
- Author
-
Pachón G, Caragol I, and Petriz J
- Subjects
- Animals, Humans, Immunophenotyping methods, Immunophenotyping standards, Leukocytes, Mononuclear immunology
- Published
- 2012
- Full Text
- View/download PDF
33. Revisiting human IL-12Rβ1 deficiency: a survey of 141 patients from 30 countries.
- Author
-
de Beaucoudrey L, Samarina A, Bustamante J, Cobat A, Boisson-Dupuis S, Feinberg J, Al-Muhsen S, Jannière L, Rose Y, de Suremain M, Kong XF, Filipe-Santos O, Chapgier A, Picard C, Fischer A, Dogu F, Ikinciogullari A, Tanir G, Al-Hajjar S, Al-Jumaah S, Frayha HH, AlSum Z, Al-Ajaji S, Alangari A, Al-Ghonaium A, Adimi P, Mansouri D, Ben-Mustapha I, Yancoski J, Garty BZ, Rodriguez-Gallego C, Caragol I, Kutukculer N, Kumararatne DS, Patel S, Doffinger R, Exley A, Jeppsson O, Reichenbach J, Nadal D, Boyko Y, Pietrucha B, Anderson S, Levin M, Schandené L, Schepers K, Efira A, Mascart F, Matsuoka M, Sakai T, Siegrist CA, Frecerova K, Blüetters-Sawatzki R, Bernhöft J, Freihorst J, Baumann U, Richter D, Haerynck F, De Baets F, Novelli V, Lammas D, Vermylen C, Tuerlinckx D, Nieuwhof C, Pac M, Haas WH, Müller-Fleckenstein I, Fleckenstein B, Levy J, Raj R, Cohen AC, Lewis DB, Holland SM, Yang KD, Wang X, Wang X, Jiang L, Yang X, Zhu C, Xie Y, Lee PPW, Chan KW, Chen TX, Castro G, Natera I, Codoceo A, King A, Bezrodnik L, Di Giovani D, Gaillard MI, de Moraes-Vasconcelos D, Grumach AS, da Silva Duarte AJ, Aldana R, Espinosa-Rosales FJ, Bejaoui M, Bousfiha AA, Baghdadi JE, Özbek N, Aksu G, Keser M, Somer A, Hatipoglu N, Aydogmus Ç, Asilsoy S, Camcioglu Y, Gülle S, Ozgur TT, Ozen M, Oleastro M, Bernasconi A, Mamishi S, Parvaneh N, Rosenzweig S, Barbouche R, Pedraza S, Lau YL, Ehlayel MS, Fieschi C, Abel L, Sanal O, and Casanova JL
- Subjects
- Adolescent, Adult, Age Factors, Child, Child, Preschool, Cytokines blood, Female, Genotype, Humans, Infant, Infant, Newborn, Interleukin-12 Receptor beta 1 Subunit genetics, Male, Middle Aged, Mycobacterium Infections, Nontuberculous epidemiology, Mycobacterium Infections, Nontuberculous genetics, Mycobacterium bovis isolation & purification, Mycobacterium tuberculosis isolation & purification, Nontuberculous Mycobacteria isolation & purification, Survival Analysis, Interleukin-12 Receptor beta 1 Subunit deficiency
- Abstract
Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guérin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years ± 9.8 years (range, 0.5-46.4 yr). IL-12Rβ1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought.
- Published
- 2010
- Full Text
- View/download PDF
34. Visceral leishmaniasis associated hemophagocytic syndrome in patients with chronic granulomatous disease.
- Author
-
Martín A, Marques L, Soler-Palacín P, Caragol I, Hernandez M, Figueras C, and Español T
- Subjects
- Adolescent, Amphotericin B therapeutic use, Animals, Antiprotozoal Agents therapeutic use, Child, Fatal Outcome, Female, Humans, Interferon-gamma therapeutic use, Leishmaniasis, Visceral diagnosis, Leishmaniasis, Visceral drug therapy, Lymphohistiocytosis, Hemophagocytic diagnosis, Lymphohistiocytosis, Hemophagocytic etiology, Male, Recombinant Proteins, Granulomatous Disease, Chronic complications, Leishmaniasis, Visceral complications, Lymphohistiocytosis, Hemophagocytic complications
- Abstract
Visceral leishmaniasis is a severe form of infection caused by a parasite endemic along the Mediterranean coast. Complications such as infection-associated hemophagocytic syndrome can occur despite correct therapy. We report visceral leishmaniasis-associated infection-associated hemophagocytic syndrome in 3 patients with chronic granulomatous disease.
- Published
- 2009
- Full Text
- View/download PDF
35. Common variable immunodeficiency: 20-yr experience at a single centre.
- Author
-
Llobet MP, Soler-Palacin P, Detkova D, Hernández M, Caragol I, and Espanol T
- Subjects
- Adolescent, Antigens, CD19, Autoimmune Diseases etiology, B-Lymphocyte Subsets immunology, B-Lymphocyte Subsets pathology, Bacterial Infections etiology, Bronchiectasis etiology, Child, Child, Preschool, Common Variable Immunodeficiency blood, Common Variable Immunodeficiency complications, Common Variable Immunodeficiency genetics, Cross-Sectional Studies, Female, Follow-Up Studies, Genetic Predisposition to Disease, Humans, Immunophenotyping, Infant, Male, Pedigree, Prognosis, Tumor Necrosis Factor Receptor Superfamily, Member 7, B-Lymphocyte Subsets metabolism, Common Variable Immunodeficiency diagnosis, Common Variable Immunodeficiency physiopathology, Immunoglobulins blood, Immunologic Memory
- Abstract
Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency. It can present at any age in patients with a history of recurrent bacterial infections, with or without a family history of other primary immunodeficiencies (PID), and shows a wide range of clinical manifestations and immunological data. Diagnosis is based on low IgG, IgM and/or IgA levels. Delayed diagnosis and therapy can lead to bronchiectasis and malabsorption. The aim of this study was to describe a paediatric population diagnosed of CVID and its evolution in the population. Memory B-cell (MB) classification carried out in these patients was correlated with clinical manifestations and outcome. Clinical and immunological data of 22 CVID children under 18 yr treated at our centre between 1985 and 2005 are presented. Immunological studies included those for diagnosis and MB quantification. Differences in form of presentation, familial incidence and MB classification were reviewed. A statistical descriptive analysis was made. Infections were the commonest manifestation, affecting mainly respiratory (19/22) and gastrointestinal (10/22) tracts. Bronchiectasis was present in seven cases, and detected prior to CVID diagnosis in five. Replacement therapy led to a significant reduction in the number of infections. Severe complications appeared mostly in patients without MB. Patients of the same family share the same MB group. Family members had also been diagnosed of CVID in seven cases. Early diagnosis and therapy are essential to improve outcome in these patients. MB studies are useful in children to orient prognosis and further genetic studies.
- Published
- 2009
- Full Text
- View/download PDF
36. Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells.
- Author
-
de Beaucoudrey L, Puel A, Filipe-Santos O, Cobat A, Ghandil P, Chrabieh M, Feinberg J, von Bernuth H, Samarina A, Jannière L, Fieschi C, Stéphan JL, Boileau C, Lyonnet S, Jondeau G, Cormier-Daire V, Le Merrer M, Hoarau C, Lebranchu Y, Lortholary O, Chandesris MO, Tron F, Gambineri E, Bianchi L, Rodriguez-Gallego C, Zitnik SE, Vasconcelos J, Guedes M, Vitor AB, Marodi L, Chapel H, Reid B, Roifman C, Nadal D, Reichenbach J, Caragol I, Garty BZ, Dogu F, Camcioglu Y, Gülle S, Sanal O, Fischer A, Abel L, Stockinger B, Picard C, and Casanova JL
- Subjects
- Cell Differentiation genetics, Cytokines genetics, Cytokines immunology, Female, Genetic Diseases, Inborn genetics, Humans, Interleukin-1 Receptor-Associated Kinases genetics, Interleukin-1 Receptor-Associated Kinases immunology, Interleukin-17 genetics, Male, Mutation, Myeloid Differentiation Factor 88 genetics, Myeloid Differentiation Factor 88 immunology, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases immunology, Quantitative Trait Loci immunology, Receptor, Transforming Growth Factor-beta Type I, Receptor, Transforming Growth Factor-beta Type II, Receptors, Interleukin-12 genetics, Receptors, Transforming Growth Factor beta genetics, Receptors, Transforming Growth Factor beta immunology, STAT3 Transcription Factor genetics, Signal Transduction genetics, Cell Differentiation immunology, Genetic Diseases, Inborn immunology, Interleukin-17 immunology, Receptors, Interleukin-12 immunology, STAT3 Transcription Factor immunology, Signal Transduction immunology, T-Lymphocytes, Helper-Inducer immunology
- Abstract
The cytokines controlling the development of human interleukin (IL) 17--producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17--producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from patients with particular genetic traits affecting transforming growth factor (TGF) beta, IL-1, IL-6, or IL-23 responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann disease and Marfan-like syndromes) and loss-of-function mutations in IRAK4 and MYD88 (Mendelian predisposition to pyogenic bacterial infections) had no detectable impact. In contrast, dominant-negative mutations in STAT3 (autosomal-dominant hyperimmunoglobulin E syndrome) and, to a lesser extent, null mutations in IL12B and IL12RB1 (Mendelian susceptibility to mycobacterial diseases) impaired the development of IL-17--producing T cells. These data suggest that IL-12Rbeta1- and STAT-3--dependent signals play a key role in the differentiation and/or expansion of human IL-17-producing T cell populations in vivo.
- Published
- 2008
- Full Text
- View/download PDF
37. Efficacy of recombinant interleukin-2 (rIL-2) in patients with advanced HIV-1 infection and blunted immune response to HAART.
- Author
-
Crespo M, Caragol I, Falcó V, Ribera E, Urban S, and Pahissa A
- Subjects
- Acquired Immunodeficiency Syndrome blood, Acquired Immunodeficiency Syndrome drug therapy, Adult, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, CD4-CD8 Ratio, CD4-Positive T-Lymphocytes metabolism, Cytokines biosynthesis, Female, Fever chemically induced, HIV Infections blood, HIV Infections drug therapy, HIV Infections immunology, Humans, Immunologic Factors adverse effects, Interleukin-2 adverse effects, Lymphopenia etiology, Male, Middle Aged, Prospective Studies, Recombinant Proteins adverse effects, Recombinant Proteins therapeutic use, Viral Load, Acquired Immunodeficiency Syndrome immunology, Immunologic Factors therapeutic use, Interleukin-2 therapeutic use, Lymphopenia drug therapy
- Abstract
Objective: The efficacy of recombinant interleukin-2 (rIL-2) was assessed in HIV-infected patients with advanced immune suppression and a discordant immune response to highly active antiretroviral therapy (HAART). The primary endpoint was median change in CD4+ T-cell counts at the end of treatment as compared to baseline. Secondary endpoints were safety and changes in the various T-cell subpopulations., Material and Methods: In a prospective cohort study, 19 patients with HIV-RNA < 50 copies/mL and < 200 CD4+ T cells/mm3 without a significant increase in the previous 12 months were scheduled to receive 6 cycles of 4.5 x 10(6) IU subcutaneous rIL-2 daily for 5 consecutive days, every 4 weeks., Results: Median age was 43 years, and 64% had a previous AIDS-defining event. Median nadir and baseline CD4+ cell counts were 36 and 99 cells/mm3, respectively. Three patients discontinued treatment and one experienced grade 4 side effects. CD4+ T-cell counts increased to 147 cells/mm3 (range, 24-285) at 1 month following completion of treatment (P = 0.002), and 180 cells/mm3 (range, 38-280) at 18 months (P < 0.001). This improvement was associated with a significant decrease in expression rates of the activation markers, HLA-DR and CD38., Conclusion: Our results suggest that in patients with advanced HIV-infection showing a blunted immune response to HAART, rIL-2 might increase the pool of CD4+ T-cells by down-regulating the status of immune activation.
- Published
- 2008
- Full Text
- View/download PDF
38. Common variable immunodeficiency: association between memory B cells and lung diseases.
- Author
-
Detková D, de Gracia J, Lopes-da-Silva S, Vendrell M, Alvarez A, Guarner L, Vidaller A, Rodrigo MJ, Caragol I, Espanol T, and Hernández M
- Subjects
- Adolescent, Adult, Aged, B-Lymphocytes immunology, Chronic Disease, Common Variable Immunodeficiency pathology, Diarrhea etiology, Diarrhea immunology, Diarrhea pathology, Female, Follow-Up Studies, Humans, Lung Diseases immunology, Lung Diseases pathology, Malabsorption Syndromes etiology, Malabsorption Syndromes immunology, Malabsorption Syndromes pathology, Male, Middle Aged, Prognosis, B-Lymphocytes pathology, Common Variable Immunodeficiency complications, Common Variable Immunodeficiency immunology, Immunologic Memory, Lung Diseases etiology
- Abstract
Background: Malabsorption syndrome often develops in patients with common variable immunodeficiency (CVID). Why structural damages appear in some CVID patients and not in others is not fully understood. Memory B cells (MBs) are responsible for the production of specific antibodies, and their defects have previously been related to autoimmune, granulomatous, and lymphoproliferative complications of CVID. The objective of this study was to ascertain whether a relationship exists between MB defects and the clinical outcome of respiratory and intestinal involvement in these patients., Methods: Forty-one CVID patients were grouped as follows, according to the quantification of peripheral MBs: the MB2 group (n = 7) included patients with normal MBs; the MB1 group (n = 16) included patients with low switched MBs; and the MB0 group (n = 18) included patients with absent/low MBs. The clinical outcome of respiratory and intestinal involvement of patients was then compared among the three groups., Results: In the MB0 group, chronic lung disease (ie, bronchiectasis and diminished FVC and/or FEV1) developed in 50% of patients vs 13% in the MB1 group and 0% in the MB2 group (p < 0.05). In the MB0 group, malabsorption syndrome or chronic noninfectious diarrhea developed in 50% of patients vs 19% in the MB1 group and 0% in the MB2 group (p < 0.05). No differences were found among the three groups for age at onset of symptoms, delay in diagnosis/treatment, months of follow-up/treatment, and prediagnostic serum IgG concentration., Conclusions: Alterations in MB count appear to be associated with a severe clinical outcome of respiratory and intestinal involvement in CVID. The MB count could be a useful laboratory parameter for orienting the prognosis and management of CVID patients.
- Published
- 2007
- Full Text
- View/download PDF
39. Pediatric HIV Infection.
- Author
-
Espanol T, Caragol I, Soler P, and Hernandez M
- Abstract
HIV infection by maternal transmission is increasing in the world due to the increase in infected women who are not receiving appropriate antiretroviral therapy. Prognosis of HIV infection in children is poor because the newborn has an immature immune system. Early diagnosis and therapy are needed to avoid the development of AIDS. New therapies are becoming available but prevention of infection, through maternal therapy during pregnancy, is the most effective measure in avoiding this infection through this transmission route.
- Published
- 2004
- Full Text
- View/download PDF
40. Clinical tuberculosis in 2 of 3 siblings with interleukin-12 receptor beta1 deficiency.
- Author
-
Caragol I, Raspall M, Fieschi C, Feinberg J, Larrosa MN, Hernández M, Figueras C, Bertrán JM, Casanova JL, and Español T
- Subjects
- Adolescent, BCG Vaccine, Child, Child, Preschool, Female, Humans, Infant, Receptors, Interleukin genetics, Receptors, Interleukin metabolism, Receptors, Interleukin-12, Salmonella Infections genetics, Salmonella Infections metabolism, Salmonella Infections physiopathology, Tuberculosis genetics, Tuberculosis physiopathology, Mycobacterium, Receptors, Interleukin deficiency, Tuberculosis metabolism
- Abstract
We describe 3 siblings with interleukin-12 receptor beta1 (IL-12Rbeta1) deficiency, a known genetic etiology of clinical disease caused by infection with poorly virulent mycobacteria, such as mycobacteria found in bacille Calmette-Guérin (BCG) vaccines and environmental nontuberculous mycobacteria (NTM). One child had disseminated tuberculosis, the second had extraintestinal salmonellosis and pulmonary tuberculosis, and the third remained asymptomatic. IL-12Rbeta1 deficiency should be considered as a diagnosis in patients with severe salmonellosis or tuberculosis, even if they do not have disease due to BCG or NTM.
- Published
- 2003
- Full Text
- View/download PDF
41. Low penetrance, broad resistance, and favorable outcome of interleukin 12 receptor beta1 deficiency: medical and immunological implications.
- Author
-
Fieschi C, Dupuis S, Catherinot E, Feinberg J, Bustamante J, Breiman A, Altare F, Baretto R, Le Deist F, Kayal S, Koch H, Richter D, Brezina M, Aksu G, Wood P, Al-Jumaah S, Raspall M, Da Silva Duarte AJ, Tuerlinckx D, Virelizier JL, Fischer A, Enright A, Bernhöft J, Cleary AM, Vermylen C, Rodriguez-Gallego C, Davies G, Blütters-Sawatzki R, Siegrist CA, Ehlayel MS, Novelli V, Haas WH, Levy J, Freihorst J, Al-Hajjar S, Nadal D, De Moraes Vasconcelos D, Jeppsson O, Kutukculer N, Frecerova K, Caragol I, Lammas D, Kumararatne DS, Abel L, and Casanova JL
- Subjects
- Adolescent, Adult, Cells, Cultured, Child, Child, Preschool, Humans, Mutation, Mycobacterium Infections immunology, Opportunistic Infections immunology, Polymorphism, Single-Stranded Conformational, Receptors, Interleukin genetics, Receptors, Interleukin physiology, Receptors, Interleukin-12, Salmonella Infections immunology, Immunity, Innate, Receptors, Interleukin deficiency
- Abstract
The clinical phenotype of interleukin 12 receptor beta1 chain (IL-12Rbeta1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rbeta1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guérin -BCG- and environmental Mycobacteria). Three patients had clinical tuberculosis, one of whom also had salmonellosis. Unlike salmonellosis, mycobacterial infections did not recur. BCG inoculation and BCG disease were both effective against subsequent environmental mycobacteriosis, but not against salmonellosis. Excluding the probands, seven of the 12 affected siblings have remained free of case-definition opportunistic infection. Finally, only five deaths occurred in childhood, and the remaining 36 patients are alive and well. Thus, a diagnosis of IL-12Rbeta1 deficiency should be considered in children with opportunistic mycobacteriosis or salmonellosis; healthy siblings of probands and selected cases of tuberculosis should also be investigated. The overall prognosis is good due to broad resistance to infection and the low penetrance and favorable outcome of infections. Unexpectedly, human IL-12 is redundant in protective immunity against most microorganisms other than Mycobacteria and Salmonella. Moreover, IL-12 is redundant for primary immunity to Mycobacteria and Salmonella in many individuals and for secondary immunity to Mycobacteria but not to Salmonella in most.
- Published
- 2003
- Full Text
- View/download PDF
42. Familial CD8 deficiency due to a mutation in the CD8 alpha gene.
- Author
-
de la Calle-Martin O, Hernandez M, Ordi J, Casamitjana N, Arostegui JI, Caragol I, Ferrando M, Labrador M, Rodriguez-Sanchez JL, and Espanol T
- Subjects
- Adult, Animals, Antibody Formation, Bacterial Infections etiology, CD8 Antigens chemistry, COS Cells, Chlorocebus aethiops, Consanguinity, Cytotoxicity, Immunologic, DNA Mutational Analysis, Dimerization, Female, Genes, Recessive, Genotype, Humans, Immunologic Deficiency Syndromes immunology, Immunologic Deficiency Syndromes pathology, Male, Molecular Sequence Data, Mutation, Pedigree, Protein Subunits, Recombinant Fusion Proteins immunology, Recurrence, Roma genetics, Spain, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets pathology, Transfection, Amino Acid Substitution, CD8 Antigens genetics, Immunologic Deficiency Syndromes genetics, Mutation, Missense
- Abstract
CD8 glycoproteins play an important role in both the maturation and function of MHC class I-restricted T lymphocytes. A 25-year-old man, from a consanguineous family, with recurrent bacterial infections and total absence of CD8(+) cells, was studied. Ab deficiencies and ZAP-70 and TAP defects were ruled out. A missense mutation (gly90-->ser) in both alleles of the immunoglobulin domain of the CD8 alpha gene was shown to correlate with the absence of CD8 expression found in the patient and two sisters. Conversely, high percentages of CD4(-)CD8(-)TCR alpha beta(+) T cells were found in the three siblings. A novel autosomal recessive immunologic defect characterized by absence of CD8(+) cells is described. These findings may help to further understanding of the role of CD8 molecules in human immune response.
- Published
- 2001
- Full Text
- View/download PDF
43. Enumeration of CD4(+) T-cells in the peripheral blood of HIV-infected patients: an interlaboratory study of the FACSCount system.
- Author
-
Lopez A, Caragol I, Candeias J, Villamor N, Echaniz P, Ortuño F, Sempere A, Strauss K, and Orfao A
- Subjects
- Cell Separation, Humans, Observer Variation, Reproducibility of Results, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes immunology, Flow Cytometry methods, HIV Infections immunology
- Abstract
The aim of the present study was to assess the interlaboratory reproducibility of the FACSCount system for the enumeration of peripheral blood (PB) CD4(+) T-cells. In each of the seven participating centers, both previously stained and unstained PB samples (n = 49) were received and either analyzed or stained and then analyzed. Interlaboratory reproducibility was checked in two different groups of centers (n = 3 and n = 4) where the study was performed in parallel. In addition, both the intralaboratory precision and accuracy of this system were analyzed in comparison with results obtained with conventional flow cytometry. Accordingly, upon comparing both methods, a high degree of correlation was observed in the total number of CD3(+) T-cells (coefficient of correlation of 0.9750 +/- 0.0184, slope of the best linear fit: 0. 9214 +/- 0.0311, y-intercept of 12 +/- 47) as well as in the number of CD3(+)/CD4(+) (coefficient of correlation of 0.9794 +/- 0.1457, slope of the best linear fit: 0.9463 +/- 0.0753, y-intercept of -11 +/- 36) and CD3(+)/CD8(+) (coefficient of correlation of 0.9728 +/- 0.0192, slope of the best linear fit: 0.9682 +/- 0.0735, y-intercept of 7 +/- 95) major subsets. In addition, low coefficients of variation (CV) were obtained for replicates, indicating the method's high degree of accuracy. The present study shows that with respect to the interlaboratory reproducibility reported for most techniques used for the enumeration of PB CD4(+) T-cells, the FACSCount system results in data with much lower coefficients of variance (CVs) (mean CV of less than 10%). Upon measuring the impact on results of different variables associated with either sample preparation or data acquisition and analysis, our study clearly shows that data acquisition and analysis does not influence the results by increasing variability since the coefficients of variation obtained for samples prepared in the same laboratory under the same conditions and read in different laboratories with different instruments were identical to those obtained for the replicates of the same samples read in each individual center. In contrast, interlaboratory variability, although low, significantly increased when sample preparation was carried out in different laboratories, suggesting that pipetting still represents the major source of variability in the FACSCount system., (Copyright 1999 Wiley-Liss, Inc.)
- Published
- 1999
- Full Text
- View/download PDF
44. Effects of anti-sense oligonucleotides directed toward dihydrofolate reductase RNA in mammalian cultured cells.
- Author
-
Rodríguez M, Noé V, Alemany C, Miralles A, Bemi V, Caragol I, and Ciudad CJ
- Subjects
- Animals, CHO Cells, Cell Division drug effects, Cricetinae, Drug Carriers, Drug Evaluation, Preclinical, Fatty Acids, Monounsaturated metabolism, Fluorescent Dyes metabolism, Humans, Liposomes, Oligonucleotides, Antisense administration & dosage, Oligonucleotides, Antisense metabolism, Quaternary Ammonium Compounds metabolism, Sensitivity and Specificity, Tetrahydrofolate Dehydrogenase genetics, Tumor Cells, Cultured, Oligonucleotides, Antisense pharmacology, RNA, Messenger antagonists & inhibitors, Tetrahydrofolate Dehydrogenase metabolism
- Abstract
The effect of incubations with anti-sense phosphorothioate oligonucleotides directed toward sequences of dihydrofolate reductase (DHFR) RNA has been tested on Chinese hamster ovary cells. The selected targets were the 5'-untranslated region, the translational start, the splice sites and branch point of intron I and polyadenylation regions 1 and 3 of the DHFR RNA. To introduce the oligonucleotides, the cationic liposome DOTAP was used. The oligonucleotides most effective at causing cytotoxicity were ATNL and DTNL, both directed toward the translation-start site, at a range of concentrations between 1 and 4 microM. The minimum time for the oligonucleotide to exert its full cytotoxic effect was 3 days. Excess of oligonucleotide diminished the cytotoxic effect. Oligonucleotide uptake was monitored by the incorporation of [32P]- or fluorescein-labeled oligonucleotide and was found to depend on liposome and oligonucleotide concentrations and duration of incubation. Formation of in vitro complexes between the oligonucleotide and the liposome was also studied. Cytotoxicity was observed when the oligonucleotide was incubated with cell lines containing either the endogenous gene or co-transfected DHFR minigenes. Cell incubation with ATNL caused a time-dependent decrease in the levels of DHFR mRNA and enzymatic activity. Moreover, a cell line bearing amplification at the dhfr locus was equally affected by the action of ATNL. Human hepatoma cells were also affected by treatment with the counterpart of ATNL in the human DHFR mRNA sequence. Our results set the basis for a possible cancer therapy with anti-sense oligonucleotides using DHFR as the target.
- Published
- 1999
- Full Text
- View/download PDF
45. Cell-growth regulation of the hamster dihydrofolate reductase gene promoter by transcription factor Sp1.
- Author
-
Noé V, Chen C, Alemany C, Nicolás M, Caragol I, Chasin LA, and Ciudad CJ
- Subjects
- Animals, Base Sequence, Binding Sites, CHO Cells, Cell Cycle genetics, Cricetinae, DNA Primers genetics, E2F Transcription Factors, Polymerase Chain Reaction, RNA, Heterogeneous Nuclear genetics, RNA, Heterogeneous Nuclear metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Retinoblastoma-Binding Protein 1, Transcription Factors metabolism, Transfection, Carrier Proteins, Cell Cycle Proteins, Cell Division genetics, DNA-Binding Proteins, Promoter Regions, Genetic, Sp1 Transcription Factor metabolism, Tetrahydrofolate Dehydrogenase genetics
- Abstract
The dihydrofolate reductase (DHFR) gene (dhfr) promoter contains cis-acting elements for the transcription factors Sp1 and E2F. Given the ability of Sp1 to activate the dhfr promoter, we have evaluated the contribution of Sp1 to the cell-growth regulation of the dhfr gene. Using gel-mobility assays performed with DNA probes from the minimal promoter of the hamster dhfr gene and nuclear extracts from cultured hamster cells (CHO K1) we show that the binding of Sp1 to the dhfr promoter is cell-growth-phase regulated. Accordingly, dhfr transcription and mRNA levels in K1 cells increase upon serum stimulation. Cytological detection of Sp1 by immunofluorescence reveals a decrease of this protein in the process leading to the G0 state, and an increase upon serum stimulation of quiescent cells. These results were confirmed by western blot analysis. It is concluded that Sp1 progressively binds to the hamster dhfr promoter after stimulation of cell proliferation, which can account for the transcriptional regulation of the dhfr gene during the cell cycle. The role of Sp1 in the specific control of dhfr during the cell cycle was confirmed in vivo using cell lines derived from dhfr-negative cells transfected with dhfr plasmids carrying either the wild-type or mutated Sp1-binding or E2F-binding sites in the dhfr minimal promoter.
- Published
- 1997
- Full Text
- View/download PDF
46. Stability of amphotericin B in an extemporaneously prepared i.v. fat emulsion.
- Author
-
Lopez RM, Ayestaran A, Pou L, Montoro JB, Hernandez M, and Caragol I
- Subjects
- Amphotericin B administration & dosage, Antifungal Agents administration & dosage, Chemistry, Pharmaceutical, Chromatography, High Pressure Liquid, Drug Stability, Drug Storage, Fat Emulsions, Intravenous administration & dosage, Humans, Particle Size, Amphotericin B chemistry, Antifungal Agents chemistry, Fat Emulsions, Intravenous chemistry
- Abstract
The stability of amphotericin B in an extemporaneously prepared i.v. fat emulsion was studied. Admixtures of amphotericin B 0.5, 1, and 2 mg/mL were prepared by adding 10, 20, and 40 mL of amphotericin B 5 mg/mL to 90, 80, and 60 mL, respectively, of 20% fat emulsion. The admixtures were stored in glass vacuum containers at 20-25 degrees C and exposed to fluorescent light, 20-25 degrees C and protected from light, or 4-8 degrees C and protected from light. A sample was withdrawn from each container at 0, 4, 12, and 24 hours and at 2, 4, 7, and 15 days for analysis of amphotericin B concentration by high-performance liquid chromatography and for visual evaluations; these samples were immediately frozen until analyzed. A sample was withdrawn from one container of amphotericin B 1 and 2 mg/mL for each storage condition at 0, 7, and 15 days for immediate determination of particle-size distribution with a fluorescinated-antibody cell sorter. Amphotericin B 0.5 mg/mL in 20% fat emulsion was stable for one week under all the storage conditions. Amphotericin B in the 1- and 2-mg/mL admixtures was stable for up to four days at 20-25 degrees C exposed to fluorescent light, and for up to one week at 20-25 degrees C protected from light and at 4-8 degrees C protected from light. There was no visible evidence of incompatibility. There were no substantial changes in particle-size distribution for the 1-mg/mL admixtures; appreciable changes were detected for the 2-mg/mL admixtures. Amphotericin B 1 and 2 mg/mL was stable in 20% fat emulsion for four days at 20-25 degrees C exposed to fluorescent light and for seven days at 20-25 degrees C protected from light or at 4-8 degrees C; amphotericin B 0.5 mg/mL was stable in 20% fat emulsion for seven days under the three storage conditions.
- Published
- 1996
- Full Text
- View/download PDF
47. Node-negative breast cancers with p53(-)/HER2-neu(-) status may identify women with very good prognosis.
- Author
-
Albanell J, Bellmunt J, Molina R, García M, Caragol I, Bermejo B, Ribas A, Carulla J, Gallego OS, Español T, and Solé Calvo LA
- Subjects
- Age Factors, Disease-Free Survival, Female, Humans, Lymphatic Metastasis pathology, Middle Aged, Neoplasm Recurrence, Local, Prognosis, Risk, Breast Neoplasms chemistry, Breast Neoplasms pathology, Neoplasm Proteins analysis, Receptor, ErbB-2 analysis, Tumor Suppressor Protein p53 analysis
- Abstract
Background: The contribution of p53 and HER-2/neu to the management of node-negative breast cancer (NNBC) could be improved by combining their results., Material and Methods: We studied paraffin-embedded primary tumors for p53 (BP-53-12-1) (n=57) and HER2/neu (pAB1) (n=63) from NNBC patients. The results were grouped in a negative (p53(-)/neu(-)) versus a positive group (one or both overexpressed). The association between both groups (negative and positive) and clinicopathologic parameters, S-phase fraction and DNA ploidy, and patients' outcome, was analyzed., Results: In 28% of the tumors p53 was overexpressed, and HER2/neu in 11%. Sixty-five percent (37 out of 57) were p53(-)/neu(-), and 35% overexpressed one (31.5%) or both (3.5%) oncoproteins. Significant correlations were found between p53(-)/neu(-) tumors and age greater than 50 (p=0.003), S-phase fraction lower than 7 (p=0.03), and positive estrogen receptor contents (p=0.049). Actuarial 5-year disease-free and overall survival for p53(-)/neu(-) tumors were 88% and 97%, respectively, versus 50% and 66%, for tumors overexpressing one or both oncoproteins (p=0.004).
- Published
- 1996
48. Malignancies in primary immunodeficient patients.
- Author
-
Español T, de Gracia J, Caragol I, Sauleda S, Garcia X, and Bertran JM
- Subjects
- Adenocarcinoma complications, Adolescent, Adult, Ataxia Telangiectasia complications, Biliary Tract Neoplasms complications, Child, Child, Preschool, Common Variable Immunodeficiency complications, Female, Humans, IgG Deficiency complications, Lymphoma complications, Male, Immunologic Deficiency Syndromes complications, Neoplasms complications
- Published
- 1993
49. Changes in peripheral blood lymphocyte patterns during early acute liver rejection: B cell increase as an index of rejection.
- Author
-
Charco R, Máñez R, Caragol I, Llopart L, Español T, and Margarit C
- Subjects
- Antibodies, Monoclonal, Antigens, CD analysis, Biomarkers, CD4 Antigens analysis, Humans, B-Lymphocytes immunology, Graft Rejection, Liver Transplantation immunology, T-Lymphocytes immunology
- Published
- 1992
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.