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1.
Leukemia ; 2(6): 363-70, 1988 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-3259660

RESUMEN

Human DNA ligase was purified from different kinds of immunocompetent cells: thymocytes, normal and stimulated lymphocytes, blasts from ALL (Burkitt and non-T, non-B) and ANLL (M1, M2, and M5). Based upon the protocol for the treatment of these leukemias, the purified enzymes were assayed in the presence of routinely used combinations of antileukemic drugs. At the range of concentration tested (between 0.1 and 5 microM) some drugs taken separately were totally inactive on the enzyme from the different sources. For those being inhibitory, when used in combination their effect was always different from what was observed when the compound was tested alone. Some combinations were more effective in inhibiting the enzyme from leukemic than from normal cells (vincristine + cyclophosphamide + prednisone in ALL and rubidazone + Ara-C, Ara-C + m-AMSA, in ANLL). However, some combinations of drugs are without effect on ligase from leukemic cells at this dose range (vincristine + rubidazone + Ara-C + prednisone and adriamycin + asparaginase + Ara-C in ALL or etoposide + Ara-C, adriamycin + cyclophosphamide in ANLL). This is the first direct observation of the effect of cytostatic drugs on DNA ligase, a key enzyme of the DNA replication and repair process. The clinical consequences of these observations are discussed in an attempt to selectively inhibit replication, thereby division, of cancer cells.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , ADN Ligasas/antagonistas & inhibidores , Leucemia/sangre , Linfocitos/enzimología , Polinucleótido Ligasas/antagonistas & inhibidores , Linfocitos T/enzimología , Adolescente , Adulto , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Daunorrubicina/análogos & derivados , Doxorrubicina/administración & dosificación , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Cinética , Leucemia/enzimología , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Vincristina/administración & dosificación
2.
Leukemia ; 8(11): 1879-83, 1994 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-7526090

RESUMEN

We investigated the prognosis value of CD34 and P-170 expression in blast cells of adult patients affected by de novo acute myeloid leukemia (AML). CD34 antigen was analyzed by indirect immunofluorescence (IFI) and alkaline phosphatase-labeled streptavidin biotine (AP-LSAB) in 62 patients (median age: 51 years). P-170 expression was determined by AP-LSAB in 51 cases using JSB1 and C219 monoclonal antibodies. All patients were treated with conventional chemotherapy induction regimen. Follow-up was from 6 to 79 months. Complete remission (CR) rate was not statistically different between CD34+ and CD34- patients (67 vs. 84%, p = 0.2). The duration of CR and survival were not influenced by CD34 expression. Karyotype abnormalities were more frequent among MDR+ patients (65 vs. 21%, p < 0.01). CR rate was statistically lower in MDR+ patients as compared to MDR- patients (63 vs. 96%, p = 0.01). Median disease-free survival (DFS) was shorter for MDR+ patients but the difference was not significant (5 vs. 10 months, p = 0.09). Patients who were positive for both parameters CD34 and P-170, had a poor prognosis with a 50 vs. 100% CR rate for CD34/P-170 negative patients, (p = 0.002), a lower median DFS (3 vs. 12 months, p = 0.01) and overall survival (OS) (3 vs. 14.5 months, p = 0.01). Results of cytogenetic analysis did not influence CR rate but the relapse rate was higher, although not significant, for the patients with unfavorable karyotype (63 vs. 33%). The seven CD34+/MDR+ patients with poor prognosis karyotype had a statistically lower CR rate, median DFS and OS than the 7 CD34-/MDR- patients with normal or favorable karyotype (CR: 29% vs. 100%, p = 0.02), (DFS: 3 vs. > 12 months, p = 0.01), (OS: 4 vs. > 12 months, p = 0.02). Our data indicate that P-170 but not CD34 expression is predictive for a lower CR rate. The identification of a bad prognosis subgroup of CD34+/MDR+ AML patients (and especially those with poor prognosis karyotype) has to be confirmed on larger series using uniform methodology.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Antígenos CD/metabolismo , Leucemia Mieloide/metabolismo , Enfermedad Aguda , Adolescente , Adulto , Anciano , Antígenos CD34 , Femenino , Humanos , Cariotipificación , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/inmunología , Leucemia Mieloide/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Factores Sexuales , Análisis de Supervivencia
3.
Leukemia ; 9(9): 1549-55, 1995 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-7658724

RESUMEN

We prospectively analyzed MDR functional activity by the Rh123 efflux assay in 84 de novo acute leukemias. Thirty of the 60 AML cases (50%) showed a positive dye efflux (in more than 10% of blast cells). In 19 cases, the dye efflux was superior to 30%. Twenty-four of the 30 efflux positive cases were CD34+ and could be studied in double staining. The mean percentage of effluxing CD34+ blast cells was 54%. There was a high correlation between CD34 expression and MDR activity (P < 10(-4)), MDR activity and PgP expression (P < 10(-6)). All the efflux negative samples were PgP negative. Nine efflux positive cases were PgP negative. Five of the 24 ALL were efflux positive. MDR activity did not correlate with FAB subtype (with the exception of AML3: 1/6 was efflux positive), age, white blood cell count or LDH level. Forty-seven AML patients were treated with conventional chemotherapy including cytarabine and an anthracycline. Thirty-one (66%) entered complete remission (CR). CR rate was statistically lower for efflux positive as compared to efflux negative patients, 46 vs 87% (P = 0.003), for PgP+ as compared to PgP- patients, 40 vs 78% (P = 0.01), for CD34+ as compared to CD34- patients, 45 vs 84% (P = 0.005). There was no correlation between P110 expression (32 AML cases studied) and FAB subtype, MDR status and clinical outcome. Two years survival was 20% for efflux positive patients as compared to 54% for efflux negative patients (P < 0.07), 15% for PgP+ vs 54% for PgP- patients (P < 0.04). The finding of efflux+/PgP- cases suggests the existence of other membrane efflux pumps. Rh123 efflux assay is straightforward in routine and could be included in MDR screening because of its potential interest in clinical outcome in AML.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Resistencia a Múltiples Medicamentos , Colorantes Fluorescentes/metabolismo , Leucemia Mieloide/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Rodaminas/metabolismo , Enfermedad Aguda , Adolescente , Adulto , Anciano , Femenino , Humanos , Leucemia Mieloide/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Fenotipo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Estudios Prospectivos , Inducción de Remisión , Rodamina 123
4.
Arch Intern Med ; 147(2): 229-31, 1987 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-3468887

RESUMEN

Seventy-three American black patients with Graves' disease were typed for HLA-A, HLA-B, and HLA-DR antigens. There was a slight increase in HLA-DRw6 antigen frequency compared with 238 normal American black controls, but this was not significant after correction for the number of antigens tested. A significant increase in HLA-DR4 and HLA-DRw6 frequency was found in a subgroup of patients with exophthalmos (22.9% and 29.2% compared with 7.6% and 10.1% of normal black controls). There was a significant increase in HLA-DRw6 in a subgroup of patients who were thyroid antibody-positive (26.0%). The increment in HLA-DRw6 was higher in 32 patients who had both exophthalmos and who were antibody positive (37.5%). A significant increase in HLA-DR5 was found in a subgroup of patients who did not have exophthalmos and who were antibody-negative (83.3%). Our findings support previous evidence for immunogenetic heterogeneity in patients with toxic Graves' disease. In American blacks HLA-DRw6 is in some way associated with the disease in contrast to the well-recognized HLA-DR3 association in whites.


Asunto(s)
Enfermedad de Graves/etnología , Antígenos HLA/genética , Negro o Afroamericano , Femenino , Frecuencia de los Genes , Enfermedad de Graves/genética , Antígenos HLA-A , Antígenos HLA-B , Antígenos HLA-DR/genética , Prueba de Histocompatibilidad , Humanos , Masculino , Estados Unidos
5.
J Clin Endocrinol Metab ; 51(4): 863-7, 1980 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-6932402

RESUMEN

HLA-A, -B, and -C antigens were tested by a standard lymphocyte microcytotoxicity technique in 86 Caucasians patients from western France with Graves' disease, and the data were compared with findings in 356 healthy controls. For HLA-DR antigen typing performed by lymphocyte microcytotoxicity testing using a long incubation time, the data were compared to findings in 100 healthy controls. An increase was found in the frequency of HLA-DRw3 [51.16% of patients vs. 20% of controls, corrected P (Pc) < 0.0003; relative risk (rr), 4.19) associated with an increased frequency of HLA-B8 (44.19% of patients vs. 22.47% of controls; Pc < 0.001; rr, 2.73) and HLA-A1 (40.7% of patients vs. 28.93% of controls; Pc < 0.03; rr, 1.71). In contrast, a diminished frequency was found for HLA-B12 (12.79% vs. 31.74%; Pc < 0.01). The antigen combination B8-DRw3 was noted in 37 of the 86 Graves' disease patients compared with 13 of 100 controls (Pc < 0.00003). No association was observed between HLA antigens and the different manifestations of the disease, such as the presence of goiter and/or exophthalmos, or the severity of clinical or biochemical signs. The present findings confirm the reported increase in the frequency of HLA-B8 in patients with Graves' disease. The most striking finding was the prevalence of HLA-DRw3, which, together with recent reports on lymphocyte-defined D locus determinants pointing to an increase frequency of HLA-Dw3, suggests that the gene or genes conferring susceptibility to Graves' disease may be located close to the HLA-D (DR) region of the sixth chromosome.


Asunto(s)
Enfermedad de Graves/inmunología , Antígenos HLA/análisis , Adolescente , Adulto , Anciano , Niño , Femenino , Enfermedad de Graves/genética , Antígenos HLA/genética , Antígenos de Histocompatibilidad Clase II/análisis , Humanos , Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Formación de Roseta
6.
J Clin Endocrinol Metab ; 74(6): 1460-4, 1992 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-1350589

RESUMEN

The present study aimed at determining the mono-, oligo-, or polyclonal nature of intrathyroid lymphocytes at the DNA level in patients with Graves' disease. Two techniques were used to seek monoclonal rearrangement in DNA derived from intrathyroidal lymphocytes obtained from six patients. The first was restriction fragment length polymorphism using two specific probes from the B-chain of T-cell receptor and the other from the heavy chain immunoglobulin gene; the second was polymerase chain reaction using a couple of specific primers from the variable and joining regions of heavy chain immunoglobulins. The results for the patients with Graves' disease were compared with those obtained for circulating T-and B-lymphocytes, granulocytes (negative controls), and T- and B-leukemic cells (positive controls). The results with restriction fragment length polymorphism favored a polyclonal origin for the lymphocytes in all cases, since no rearrangement was visualized. The results with polymerase chain reaction were analogous, and the technique was 10 times more sensitive in the detection of rearrangement.


Asunto(s)
Linfocitos B/inmunología , Reordenamiento Génico , Enfermedad de Graves/genética , Enfermedad de Graves/inmunología , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Receptores de Antígenos de Linfocitos B/genética , Receptores de Antígenos de Linfocitos T/genética , Linfocitos T/inmunología , Glándula Tiroides/inmunología , Adulto , Secuencia de Bases , ADN/genética , ADN/aislamiento & purificación , Desoxirribonucleasa BamHI , Desoxirribonucleasa HindIII , Femenino , Humanos , Masculino , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos
7.
J Clin Endocrinol Metab ; 57(4): 719-22, 1983 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-6688428

RESUMEN

One hundred and eleven unselected patients with hyperthyroidism due to Graves' disease received decreasing doses of carbimazole for 18 months. Clinical examination and hormonal assays (serum T3, T4, free T4 index) were done at 4, 9, and 18 months of treatment. Patients were typed for 35 HLA antigens and were followed for 2 yr after withdrawal of treatment; 39 patients were excluded for various reasons and 72 were retained for study. Of the 72 patients, 37 relapsed and 35 remained in remission; 40 patients were DR3+ (20 relapsed) and 32 were DR3- (17 relapsed). HLA frequency was not significantly different in patients who relapsed and those who remained in remission. Thus, under the conditions of this study, HLA frequency could not be used to predict relapse of hyperthyroidism due to Graves' disease.


Asunto(s)
Carbimazol/uso terapéutico , Enfermedad de Graves/inmunología , Antígenos HLA/análisis , Enfermedad de Graves/complicaciones , Enfermedad de Graves/tratamiento farmacológico , Humanos , Hipertiroidismo/tratamiento farmacológico , Hipertiroidismo/etiología , Hipertiroidismo/inmunología , Estudios Prospectivos , Recurrencia
8.
J Clin Endocrinol Metab ; 62(1): 117-21, 1986 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-3484386

RESUMEN

Markers of autoimmunity in hyperthyroid Graves' disease were studied at various stages of the disease in connection with HLA status. The 148 patients studied were included in a long term prospective evaluation of antithyroid drug treatment. The proportions of total T lymphocytes and OKT4 and OKT8 positive cells in peripheral blood and circulating thyroid-stimulating antibodies were determined before treatment (M0; 46 patients), after 6 (M6; 50 patients), and 18 months (M18; 22 patients) of carbimazole treatment, at relapse (15 patients) and after 2 yr of euthyroidism after drug withdrawal (remission; 23 patients). Twenty-seven patients were sequentially studied between M0 and M6, and M6 and M18. As compared to matched normal subjects, the mean proportion of OKT8 positive cells was significantly decreased in every group of patients, even in those in remission, and the mean OKT4/OKT8 cell ratios were increased in all groups except the patients in remission. However, OKT4/OKT8 cell ratios in individual M0 patients were widely distributed, being normal in 50%. No correlation was found between the proportions of T cell subsets and thyroid-stimulating antibody values, and the two measures varied independently in patients studied sequentially. OKT8 lymphocyte subset was dependent on HLA status. In DR3-positive patients, the mean OKT4/OKT8 cell ratio was high at all stages of the study; in DR3-negative patients it decreased significantly at M18 and was normal in those patients who had a remission. However, in the DR3-positive and -negative groups of patients, the mean OKT4/OKT8 ratios at M0 and at relapse were similar. In conclusion, the proportions of circulating OKT8 positive lymphocytes reflect only poorly the activity of the immune abnormalities in Graves' disease, but do correlate with HLA-DR3 status.


Asunto(s)
Anticuerpos/análisis , Carbimazol/uso terapéutico , Enfermedad de Graves/inmunología , Antígenos HLA/análisis , Linfocitos T/clasificación , Tirotropina/inmunología , Adolescente , Adulto , Anciano , Enfermedades Autoinmunes/inmunología , Niño , Femenino , Enfermedad de Graves/tratamiento farmacológico , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología
9.
J Clin Endocrinol Metab ; 70(3): 675-9, 1990 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-1689737

RESUMEN

A prospective randomized study was performed in patients with hyperthyroid Graves' disease (GD) in order to compare long (18 months) and short term (6 months) antithyroid drug treatment on the remission rate. A therapeutic protocol was offered to all GD patients who had not been treated for this disease previously. All patients studied who followed the protocol were rechecked 2 yr after treatment was withdrawn, or earlier in the case of relapse. Of the patients having undergone long term treatment, 61.8% still were in remission 2 yr after treatment withdrawal, whereas only 41.7% of the patients treated for 6 months were in remission (P less than 0.05). Such findings clearly establish that treatment duration has a direct beneficial incidence on the remission rate. These results were confirmed by the fact that treatment for 18 months resulted in remission in 7 of 15 patients who had previously relapsed after a 6-month course of therapy. This improvement in relation to treatment duration might be due to the immunosuppressive action of carbimazole. No significant difference was observed between relapse and remission groups, regardless of treatment duration, for HLA ABDr, serum T3 and T4, and T3/T4 ratio determined before treatment. Only the thyroid-stimulating antibody levels determined at the time of diagnosis and at the end of treatment were higher in the relapse group, a difference that was relevant only globally, due to value scattering. Furthermore, thyroid-stimulating antibody levels at the end of treatment may indicate remission or, conversely, continuance of the pathological process.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Antitiroideos/uso terapéutico , Enfermedad de Graves/tratamiento farmacológico , Adulto , Anticuerpos/análisis , Carbimazol/uso terapéutico , Femenino , Enfermedad de Graves/sangre , Enfermedad de Graves/inmunología , Antígenos HLA/análisis , Humanos , Masculino , Estudios Prospectivos , Distribución Aleatoria , Hormonas Tiroideas/sangre , Factores de Tiempo
10.
Am J Med ; 102(1): 14-20, 1997 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9209196

RESUMEN

PURPOSE: The Polycythemia Vera Study Group (PVSG) has established useful criteria for the diagnosis of polycythemia vera. In some circumstances, an increase of plasma volume (PV) masks that of red cell mass (RCM), with hemoglobin (Hb) and hematocrit (Ht) remaining normal. This defines the concept of inapparent polycythemia. PATIENTS AND METHODS: One hundred and three patients seen in the hematology unit with the diagnosis of polycythemia vera were studied. There were 55 males and 48 females with a median age of 59 years. Ninety-five patients fulfilled the PVSG criteria. Spontaneous erythroid colonies and low serum erythropoietin level confirmed the diagnosis in the 8 other cases. Patients were classified according to Hb and Ht level. RESULTS: Group A consisted of 85 patients with increased Hb and Ht defined, respectively, by Hb > 18 g/dl, Ht > 0.52 in males and Hb > 16 g/dL, Ht>0.47 in females. Group B included 18 patients (17%) with inapparent polycythemia vera (IPV) defined by a normal Hb and Ht value at diagnosis. In this group, the reasons to perform RCM were as follows: splenomegaly associated with increased platelets and/or leucocytes counts (n = 8), portal vein thrombosis (n = 5), increased platelets or leucocytes counts without splenomegaly (n = 3), and isolated splenomegaly (n = 2). The two groups were balanced in terms of age, sex, leucocyte, serum iron, and platelet level. Hemoglobin and Ht levels were significantly different between the two groups. The difference between the PV was indeed highly significant. The mean PV increase was + 9.5% (nL < +20%) in group A versus + 36.3% in group B (P < 0.00005). Red cell mass was not different between the two groups. CONCLUSIONS: Increased Hb or Ht should constitute the sole criteria for RCM determination. In the context of portal vein thrombosis, isolated hyperleucocytosis, thrombocytosis, or splenomegaly, a RCM should be performed. The frequency of IPV remains to be specified but the diagnosis of polycythemia vera is probably underestimated.


Asunto(s)
Policitemia Vera/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Recuento de Eritrocitos , Femenino , Hematócrito , Hemoglobinas/metabolismo , Humanos , Masculino , Persona de Mediana Edad
11.
Transplantation ; 30(2): 114-7, 1980 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7010705

RESUMEN

Anti-HLA-A,B and anti-B lymphocyte antibodies were screened as part of a prospective alloimmunity monitoring study in 29 renal allograft recipients using a standard microlymphocytotoxicity test. Warm-reactive and/or cold-reactive lymphocytotoxins were directed against a panel of B lymphocytes, the donor's B lymphocytes, and the recipient's own B lymphocytes. A small proportion of patients had pretransplant antibodies, whereas about one-half of the patients had post-transplant antibodies. One-year allograft survival rates were lower among the patients with warm- and cold-reactive sera than among those with nonreactive sera or pure B cold-reactive sera. The sera of 20 patients were tested against donor B lymphocytes. The presence of donor-specific antibodies correlated closely enough with graft loss to be of predictive value. Autoantibodies appeared to have an enhancing effect in this study.


Asunto(s)
Suero Antilinfocítico/inmunología , Linfocitos B/inmunología , Trasplante de Riñón , Especificidad de Anticuerpos , Rechazo de Injerto , Antígenos HLA/inmunología , Humanos , Pronóstico , Estudios Prospectivos , Trasplante Homólogo
12.
Transplantation ; 38(3): 227-30, 1984 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-6382711

RESUMEN

The outcome of 893 prospectively typed (HLA-A, B, and DR) and matched cadaveric kidney transplants--all first grafts, with patients being transfused before transplantation--was studied using actuarial survival methods. The effect of HLA-A, B and DR matching was only found to be significantly beneficial to graft survival in the group of 289 presensitized recipients: 70% and 43% graft survival at two years in the case of best-matched (4-6 HLA-A, B, and DR) identities versus mismatched (0 and 1 HLA-A, B, and DR) identities, respectively (P = 0.05). Although a cumulative effect of matching for antigens belonging to the 3 HLA-A, B, and DR series was observed among the group of preimmunized recipients, a trend arose in favor of the prominent role of the HLA-B alleles. No significant difference related to HLA matching was observed in the group of nonsensitized recipients. These results confirm previous observations and support efforts to give priority for matched kidneys to preimmunized patients.


Asunto(s)
Supervivencia de Injerto , Prueba de Histocompatibilidad , Inmunización , Trasplante de Riñón , Análisis Actuarial , Antígenos HLA/análisis , Antígenos HLA/inmunología , Antígenos HLA-A , Antígenos HLA-B , Antígenos HLA-DR , Antígenos de Histocompatibilidad Clase II/análisis , Antígenos de Histocompatibilidad Clase II/inmunología , Humanos
13.
Immunol Lett ; 5(5): 233-7, 1982 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-6984424

RESUMEN

Monoclonal antibody production recognizing the HLA-A3 antigen is described. The XI-23 antibody reacted with all of the 89 cell suspensions carrying the HLA-A3 antigen (100% cytotoxicity) among a total of 191 suspensions tested. No extra-reactivity or cross-reactivity was observed, particularly with that of HLA-A11. This antibody can thus be considered as a good HLA-typing reagent.


Asunto(s)
Anticuerpos Monoclonales/biosíntesis , Antígenos HLA/inmunología , Animales , Citotoxicidad Inmunológica , Femenino , Antígenos HLA/genética , Antígeno HLA-A3 , Hemocromatosis/genética , Hemocromatosis/inmunología , Humanos , Ratones , Ratones Endogámicos BALB C , Linaje
14.
Hum Immunol ; 59(8): 524-8, 1998 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9712358

RESUMEN

The class Ib HLA-G gene encodes for a molecule which is selectively expressed in fetal placental cells. Fetomaternal tolerance could be partially explained by the interactions between HLA-G molecules and KIR receptors of decidual NK cells. To determine whether the presence of HLA-G antigens might constitute a factor of immune tolerance during the tumoral process, we compared the expression of the HLA-G gene in normal and malignant hematopoietic cells. Despite a HLA-G transcriptional activity in several lymphocytes and monocytes, no antigens are found at the cell surface or in the cytosol using the specific HLA-G mAb, 87G. This lack of expression does not appear modified in malignant hematopoietic cells. However, treatment of the monohistiocytic cell line U937 with different cytokines enabled the expression of HLA-G antigens to be induced. We suggest that the potential induction of HLA-G molecules in monocytic malignant cells following secretion of cytokines may constitute a factor of immune tolerance in patients.


Asunto(s)
Expresión Génica , Genes MHC Clase I/genética , Antígenos HLA/genética , Antígenos de Histocompatibilidad Clase I/genética , Leucemia/genética , Linfoma de Células B/genética , Línea Celular Transformada/efectos de los fármacos , Citocinas/farmacología , Cartilla de ADN/química , Citometría de Flujo , Antígenos HLA/metabolismo , Antígenos HLA-G , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Técnicas para Inmunoenzimas , Leucemia/metabolismo , Leucocitos/metabolismo , Linfoma de Células B/metabolismo
15.
Hum Immunol ; 17(1): 3-20, 1986 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-3488984

RESUMEN

New class I antigens in linkage disequilibrium with HLA-A antigen are demonstrated in PHA T and EBV preferential target cells using human alloantisera. These new antigens are defined as class I antigens by immunoprecipitation of a 41-12 k dimer. The molecule is shown to be distinct from the HLA-A, -B, -C molecule and in particular from the A3 molecule as in sequential immunoprecipitations, the depletion of the HLA-A, -B, -C molecule or A3 molecule (44-12 k) has no effect on the new molecule (41-12 k). Being present on the PHA T cells and lymphoblast lines, these antigens are considered as new epitopes involved in the the cell activation process.


Asunto(s)
Antígenos HLA/análisis , Linfocitos/inmunología , Linfocitos B/inmunología , Células Cultivadas , Niño , ADN/análisis , Femenino , Citometría de Flujo , Antígenos HLA/genética , Humanos , Leucemia Linfoide/inmunología , Linfocitos/citología , Linfocitos T/inmunología
16.
Hum Immunol ; 38(3): 206-12, 1993 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-7906261

RESUMEN

HLA-G gene polymorphism was analyzed by RFLP using seven restriction enzymes and an HLA-G locus-specific probe. Hybridization of 55 DNAs digested with three enzymes (Taq I, Pst I, and Bgl II) revealed two polymorphic bands in each case. RFLP patterns obtained with Taq I and Pst I corresponded to the same allelic polymorphism and differed from the Bgl II polymorphism. Combining both polymorphisms enabled determination of four alleles. Allelic frequencies were calculated: 40% of the subjects tested had allele 1, 36% had allele 2, 22% had allele 3, and 2% had allele 4. Analyzing the complete HLA class I phenotype revealed strong linkage disequilibrium with the HLA-A locus. The polymorphism described is located in the 3' flanking region of the gene. Moreover, extended HLA-A haplotypes were constructed by combining the HLA-G polymorphism with other class-I-sequence polymorphisms.


Asunto(s)
Genes MHC Clase I , Antígenos HLA/genética , Antígenos de Histocompatibilidad Clase I/genética , Polimorfismo Genético , Secuencia de Bases , Frecuencia de los Genes/fisiología , Antígenos HLA-G , Humanos , Desequilibrio de Ligamiento , Datos de Secuencia Molecular , Polimorfismo de Longitud del Fragmento de Restricción
17.
Hum Immunol ; 62(2): 106-12, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11182219

RESUMEN

Tumor necrosis factor alpha (TNFalpha) is a pleiotropic cytokine involved in inflammatory responses which can trigger both cell apoptosis and cell activation. In antigen presenting cells (APC), TNFalpha increased antigen presentation, notably by up-regulation of HLA class II expression. In addition to their role in antigen presentation, HLA-DR molecules transduce intracellular signals which lead to cytokine up-regulation or cell death. We have previously observed that the susceptibility of APC to HLA-DR mediated apoptosis increase throughout their maturation. We therefore investigated the relationship between TNFalpha production and susceptibility to HLA-DR-mediated apoptosis of different APC. The hematopoietic progenitor cell line (KG1), monocytic cell line (THP-1), monocyte-derived dendritic cell (DC), and B-lymphoid cell line (Raji) have been studied. We report that apoptosis susceptibility and spontaneous TNFalpha release are correlated in these different cells. However, while autocrine TNFalpha production was critical for DC maturation, upregulation of TNFalpha release after HLA-DR crosslinking was not observed and neutralization of endogenous TNFalpha did not modify HLA-DR-mediated apoptosis. These data reveal that HLA-DR mediated apoptosis susceptibility and spontaneous TNFalpha release are regulated in a parallel manner and that while TNFalpha may induce maturation of APC to an "apoptosis sensitive" stage, there is no direct role for TNFalpha in HLA-DR-mediated apoptosis of APC.


Asunto(s)
Células Presentadoras de Antígenos/inmunología , Células Presentadoras de Antígenos/metabolismo , Apoptosis/inmunología , Antígenos HLA-DR/fisiología , Factor de Necrosis Tumoral alfa/metabolismo , Linfoma de Burkitt/inmunología , Linfoma de Burkitt/patología , Diferenciación Celular/inmunología , Supervivencia Celular/inmunología , Técnicas de Cocultivo , Células Dendríticas/citología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Antígenos HLA-DR/biosíntesis , Humanos , Inmunidad Innata , Leucemia Monocítica Aguda/inmunología , Leucemia Monocítica Aguda/patología , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/patología , Células Tumorales Cultivadas/inmunología , Células Tumorales Cultivadas/patología
18.
Hum Immunol ; 62(10): 1073-80, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11600213

RESUMEN

P-glycoprotein (P-gp), an ATP-binding cassette (ABC) drug efflux pump, has been recently shown to play an important role in the physiology of Langherans cells, a subtype of dendritic cells (DC) found in the skin. The present study was designed to investigate expression and activity of P-gp and of multidrug resistance-associated protein (MRP), another ABC efflux pump sharing numerous substrates with P-gp, in human monocyte-derived DC. Immunolabeling experiments and dye efflux assays indicated that such cells displayed elevated levels of MRP activity and expression when compared to those present in parental monocytes. Generation of DC from monocytes in the presence of the MRP inhibitor indomethacin did not, however, alter the capacity of DC to stimulate allogeneic T cells proliferation in mixed lymphocyte reaction. In addition, indomethacin did not inhibit the up-regulation of the CD1a, a marker occurring during the differentiation of monocytes into DC. In contrast to that of MRP, functional expression of P-gp was not detected in monocyte-derived DC. Such antigen presenting cells that constitute a promising tool for antitumor vaccinal therapy therefore display differential expression of the efflux pumps P-gp and MRP.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/biosíntesis , Células Dendríticas/metabolismo , Resistencia a Múltiples Medicamentos/inmunología , Monocitos/metabolismo , Transporte Biológico/efectos de los fármacos , Transporte Biológico/inmunología , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/inmunología , Células Cultivadas , Técnicas de Cocultivo , Células Dendríticas/citología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Fluoresceínas/metabolismo , Técnica del Anticuerpo Fluorescente Indirecta , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Células HL-60 , Humanos , Inmunofenotipificación , Interleucina-4/farmacología , Células K562 , Prueba de Cultivo Mixto de Linfocitos , Monocitos/citología , Monocitos/efectos de los fármacos , Monocitos/inmunología , Probenecid/farmacología
19.
Hum Immunol ; 29(2): 143-9, 1990 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-1979072

RESUMEN

Using RFLP, the present study sets off to determine the MHC class II gene polymorphism in Graves' disease, in order to define the HLA-related genetic susceptibility. Considering the preferential link between Graves' disease and the HLA-DR3 antigen, 42 HLA-DR3 Graves' disease patients were studied and compared with 42 HLA-DR-matched controls. Hybridization with a DQ alpha probe of DNAs digested by Taq I revealed a polymorphism of the DR3 haplotype with an overrepresentation of a 2.1 kb(U) fragment in patients, but this was merely a sign of the linkage disequilibrium between U and B8DR3. Hybridization with the DR beta probe of DNAs digested by Taq I yielded more facts. It revealed the overrepresentation of the Dw24 specificity (Taq I:9.8 kb) in DR3 Graves' disease patients. This study thus enabled us to determine precisely the susceptibility linked to the DR3 haplotype, implicating the DRB3 gene and its Dw24 allele, which appear to be the most reliable markers of the disease, providing a higher relative risk than B8DR3.


Asunto(s)
Enfermedades Autoinmunes/genética , Genes MHC Clase II , Enfermedad de Graves/genética , Antígenos HLA-DR/genética , Alelos , Desoxirribonucleasas de Localización Especificada Tipo II , Susceptibilidad a Enfermedades , Frecuencia de los Genes , Genotipo , Antígenos HLA-DQ/genética , Subtipos Serológicos HLA-DR , Humanos , Fenotipo , Polimorfismo de Longitud del Fragmento de Restricción , Factores de Riesgo
20.
Hum Immunol ; 60(7): 598-607, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10426277

RESUMEN

Cord blood is increasingly used in transplantation as it is a readily available source of progenitor cells and is reputed to generate less severe graft-versus-host disease (GVHD) than adult bone marrow. We have compared apoptosis of cord blood lymphocytes (CB) and adult lymphocytes (PBMC) after stimulation via HLA class I, HLA class II or CD3 in order to reproduce in vitro some of the stimuli occurring after allotransplantation. CB spontaneously apoptose more than PBMC ex vivo, stimulation via HLA class I dramatically increased CB apoptosis without altering viability of PBMC. Expression of Fas was markedly lower on CB than on PBMC and this difference was maintained even after activation. Fas ligand was expressed in CB and in PBMC. CB were activated via either HLA class I or class II molecules although proliferation was not observed. Only phorbol ester pre-activation allowed Fas to subsequently induce a death signal. Proliferation of PBMC via CD3 led to enhanced Fas signals. CB therefore differ from PBMC with regard to both spontaneous and activation induced apoptosis and either allo- or CD3 mediated stimulation. Finally, the apoptosis of CB via HLA-class I could have an important role in the moderation of graft-versus-host disease.


Asunto(s)
Apoptosis , Sangre Fetal/inmunología , Receptor fas/biosíntesis , Adulto , Complejo CD3/inmunología , Proteína Ligando Fas , Sangre Fetal/citología , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Humanos , Glicoproteínas de Membrana/biosíntesis , Modelos Inmunológicos
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