RESUMEN

OBJECTIVE: The aim of this study was to identify any correlations between microvascular damage, assessed by nailfold videocapillaroscopy and skin impairment, evaluated by three different methods, the modified Rodnan skin score (mRSS), skin high-frequency ultrasound (US) and the plicometer skin test (PST) in systemic sclerosis (SSc) patients. METHODS: Sixty-three SSc patients and 63 healthy subjects were enrolled. Nailfold videocapillaroscopy (NVC) was used to assess the nailfold capillaroscopy pattern ("Early", "Active" or "Late"), according to the Cutolo classification. All subjects were assessed by mRSS, US and PST to evaluate their dermal thickness (DT) in the seventeen skin areas of the body usually evaluated by mRSS (zygoma, fingers, hands, dorsum of hands, forearms, arms, chest, abdomen, thighs, legs, feet). Statistical evaluation was performed by nonparametric tests. RESULTS: All the three methods demonstrated progressively higher values of skin impairment in patients with "Early", "Active" or "Late" pattern of nailfold microangiopathy (for mRSS p < 0.01, US p < 0.02 and PST p < 0.02). A positive correlation was also observed in SSc patients between the three methods used to evaluate skin involvement (mRSS vs US, mRSS vs PST, PST vs US, p < 0.0001 respectively). CONCLUSIONS: This study demonstrates that there is a correlation between two of the most important aspects to classify and monitor the SSc patients, i.e. microvascular damage progression (evaluated by NVC) and skin damage (assessed by mRss, US and PST).

Asunto(s)

Capilares/patología , Angioscopía Microscópica , Uñas/irrigación sanguínea , Esclerodermia Sistémica/patología , Piel/irrigación sanguínea , Piel/patología , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Esclerodermia Sistémica/diagnóstico por imagen , Índice de Severidad de la Enfermedad , Ultrasonografía

RESUMEN

Hashimoto's encephalopathy (HE) is an autoimmune form of encephalopathy, associated with autoimmune thyroiditis. Its prevalence is estimated to be 2:100,000. HE is characterized by behavioral changes, mental confusion, dysarthria, ataxia, psychosis, paranoia, convulsions, hallucinations, headache and hyperthermia. Elevated thyroid antibodies are necessary for diagnosis and the disease responds dramatically to glucocorticoid therapy. We describe a patient with HE and panniculitis, an association reported twice in the literature.

Asunto(s)

Encefalitis/complicaciones , Enfermedad de Hashimoto/complicaciones , Paniculitis/complicaciones , Anciano , Humanos , Masculino

RESUMEN

Inflammatory and immunologic mechanisms are important for the initiation and the progression of atherosclerotic lesions. OxLDL and HSP-60 antigens are involved in the pathogenesis of atherosclerotic disease by triggering immune cells within the plaques. Through the MHC pentamer assays, we investigated the presence of OxLDL- and HSP-60-specific CD8(+) T lymphocytes in twenty HLA-A2-positive patients suffering from coronary artery disease (10 NSTEMI and 10 stable angina). Similarly, 10 age- and sex-matched healthy subjects were enrolled as controls. Biological samples were collected within 6 h of admission to hospital, at 30 days and at 180 days. OxLDL- and HSP-60-specific CD8(+) T lymphocytes were never detectable in the peripheral blood from all the healthy controls. On the contrary, at each scheduled time point, both of these specific cells could be detected in peripheral blood from all enrolled patients. More in detail, the flow cytometric analysis of MHC-1 pentamer OxLDL-specific CD8(+) T lymphocytes revealed a sharp and significant increase at the hospital admission, within 6 h from the chest pain onset, followed by an evident decline to lower levels at 30 days and at 180 days from the enrollment in the study. On the contrary, although MHC-1 pentamer HSP-60 CD8(+) T lymphocytes were detectable in enrolled patients, almost no variance could be detectable during the follow-up scheduled evaluations. On the whole, this finding indicates that HSP-60- and OxLDL-specific CD8(+) T lymphocytes could play a role in the maintenance or worsening of the atherosclerotic coronary disease.

Asunto(s)

Linfocitos T CD8-positivos/inmunología , Chaperonina 60/inmunología , Enfermedad de la Arteria Coronaria/inmunología , Enfermedad de la Arteria Coronaria/patología , Lipoproteínas LDL/inmunología , Proteínas Mitocondriales/inmunología , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

OBJECTIVES: To measure the prevalence of, and factors associated with, left ventricular (LV) dysfunction in systemic sclerosis (SSc). METHODS: The EUSTAR database was first searched. A case-control study of a patient subset was then performed to further identify independent factors associated with LV dysfunction by simple and multiple regression. RESULTS: Of 7073 patients, 383 (5.4%) had an LV ejection fraction (EF) of <55%. By multiple regression analysis, age, sex, diffuse cutaneous disease, disease duration, digital ulcerations, renal and muscle involvement, disease activity score, pulmonary fibrosis and pulmonary arterial hypertension were associated with LV dysfunction. In the second phase, 129 patients with SSc with LVEF <55% were compared with 256 patients with SSc with normal LVEF. Male sex (OR 3.48; 95% CI 1.74 to 6.98), age (OR 1.03; 95% CI 1.01 to 1.06), digital ulcerations (OR 1.91; 95% CI 1.05 to 3.50), myositis (OR 2.88; 95% CI 1.15 to 7.19) and use of calcium channel blockers (OR 0.41; 95% CI 0.22 to 0.74) were independent factors associated with LV dysfunction. CONCLUSION: The prevalence of LV dysfunction in SSc is 5.4%. Age, male gender, digital ulcerations, myositis and lung involvement are independently associated with an increased prevalence of LV dysfunction. Conversely, the use of calcium channel blockers may be protective.

Asunto(s)

Esclerodermia Sistémica/complicaciones , Disfunción Ventricular Izquierda/etiología , Adulto , Factores de Edad , Anciano , Bloqueadores de los Canales de Calcio/uso terapéutico , Métodos Epidemiológicos , Europa (Continente)/epidemiología , Femenino , Dedos , Humanos , Masculino , Persona de Mediana Edad , Miositis/complicaciones , Miositis/epidemiología , Esclerodermia Sistémica/epidemiología , Factores Sexuales , Úlcera Cutánea/complicaciones , Úlcera Cutánea/epidemiología , Volumen Sistólico , Disfunción Ventricular Izquierda/epidemiología , Disfunción Ventricular Izquierda/prevención & control

RESUMEN

CONTEXT: The recent Third International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism (PHPT) set 60 ml/min as the precise level of glomerular filtration rate (GFR) below which surgery is recommended because it is considered a threshold of concern in patients with PHPT. OBJECTIVE: The aim of the study was to investigate the relationship between different stages of renal insufficiency and PTH levels in PHPT patients. DESIGN: We conducted a cross-sectional study. PATIENTS AND METHODS: We studied 294 consecutive PHPT patients. Biochemical evaluation included total and ionized serum calcium, phosphate, creatinine, immunoreactive intact PTH, and 25-hydroxyvitamin D3 levels in the fasting state. GFR was assessed with the Modification of Diet in Renal Disease Study formula. RESULTS: The mean GFR of the whole group of PHPT patients was 92.3 +/- 31.6 ml/min x 1.73 m(2). The patients were divided into four groups according to National Kidney Foundation Disease Outcomes Quality Initiative (K/DOQI) guidelines: group 1 with normal or increased GRF (>90 ml/min x 1.73 m(2); n = 153); group 2 with mild decreased GFR (60-89 ml/min x 1.73 m(2); n = 90); group 3 with moderately decreased GFR (30-59 ml/min x 1.73 m(2); n = 45); and group 4 with severely decreased GFR (<30 ml/min x 1.73 m(2); n = 6). PTH levels were comparable across groups 1-3, whereas group 4 showed significantly higher PTH levels (P < 0.0001). CONCLUSION: In our series of PHPT patients, only a severe impairment of GFR was characterized by a further PTH increase. These findings challenge the concept of a PTH elevation below the threshold of 60 ml/min of GFR.

Asunto(s)

Tasa de Filtración Glomerular , Hiperparatiroidismo Primario/fisiopatología , Hormona Paratiroidea/sangre , Adulto , Anciano , Presión Sanguínea , Calcifediol/sangre , Calcio/sangre , Creatinina/sangre , Estudios Transversales , Femenino , Humanos , Hiperparatiroidismo Primario/sangre , Italia , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/metabolismo , Fosfatos/sangre , Población Blanca

RESUMEN

BACKGROUND AND AIM: To evaluate cardiovascular abnormalities in highly active antiretroviral therapy (HAART) treated HIV patients with no signs or symptoms of cardiovascular impairment, and to assess the relative role of multiple concomitant risk factors. METHODS AND RESULTS: Forty-four consecutive HIV subjects (mean age 41+/-6 yrs) were enrolled. Inclusion criteria were HIV infection, CD4+cell count>150/ml, HAART treatment for at least 4 years. Metabolic serum levels, morphological and functional echocardiographic parameters were assessed in all subjects. Sixteen healthy age and sex matched subjects with no cardiovascular risk factors were recruited as controls. HIV patients showed increased left ventricular mass index with reduced mid-wall fractional shortening (mFS) when compared to controls (50.2+/-10.5 vs. 38.6+/-14.4, p=0.05 and 18.3+/-0.6 vs. 21.9+/-0.7, p<0.05, respectively). Twenty-nine patients were lipodystrophic (LD) and showed a longer HAART period (p=0.0004) and greater use of protease inhibitors (PI) (p=0.001). Coronary flow reserve (CFR) was significantly reduced in HIV patients as compared to controls (p<0.0001), as it was in LD subjects when compared to non-lipodystrophic ones (NLD) (p<0.001). Adiponectin concentrations were found to be significantly lower in LD subjects than in NLD ones (7.8+/-0.8 vs. 13.8+/-1.2 microg/ml, p=0.01), and showed a direct correlation with CFR. In multiple regression analysis, insulin, HDL and adiponectin accounted for 63% of CFR variations. CONCLUSIONS: Left ventricular hypertrophy, depressed mFS and reduced CFR represent the main signs of subclinical cardiac damage in HIV subjects treated with HAART. Hypoadiponectinemia in these subjects seems to be a metabolic risk factor of cardiovascular impairment.

Asunto(s)

Infecciones por VIH/tratamiento farmacológico , Síndrome de Lipodistrofia Asociada a VIH/sangre , Hipertrofia Ventricular Izquierda/etiología , Adiponectina/sangre , Adulto , Terapia Antirretroviral Altamente Activa/efectos adversos , Recuento de Linfocito CD4 , Estudios de Casos y Controles , Circulación Coronaria , Regulación hacia Abajo , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Síndrome de Lipodistrofia Asociada a VIH/complicaciones , Humanos , Hipertrofia Ventricular Izquierda/sangre , Hipertrofia Ventricular Izquierda/fisiopatología , Insulina/sangre , Lipoproteínas HDL/sangre , Modelos Logísticos , Masculino , Persona de Mediana Edad , Contracción Miocárdica , Medición de Riesgo , Factores de Riesgo , Función Ventricular Izquierda

RESUMEN

Systemic sclerosis (SSc) is a complex and heterogeneous autoimmune disorder with a multi-factorial pathogenesis. Like other autoimmune disorders, the possible role of specific cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms in predisposing to SSc has been hypothesized, but it remains controversial. CTLA-4 promoter (-318C/T) and exon 1 (+49 A/G) polymorphisms have been analysed in 43 Italian females with SSc and in 93 unrelated matched healthy controls by a newly designed tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method. No significant association has been found with either polymorphisms.Nevertheless, SSc patients without concomitant Hashimoto's thyroiditis (HT) were carrying both the -318T allele (P = 0.031) and the +49 G allele (P = 0.076) more frequently than SSc patients with HT [defined by positivity for anti-thyroperoxidase (TPO) and anti-thyroglobulin (TGA) autoantibodies] than controls. Haplotype analysis confirms this association (P = 0.028), and suggests the predominant role of the -318T, whereas that of the +49 G, if any, seems weak. Thus, in Italian SSc patients the CTLA-4 -318C/T promoter polymorphism appears to be associated with the susceptibility to develop SSc without thyroid involvement. Larger studies are needed to confirm these findings and to clarify whether the -318C/T polymorphism is the functional responsible or whether it reflects the presence of another linked genetic element in the same chromosomal region.

Asunto(s)

Antígenos CD/genética , Antígenos de Diferenciación/genética , Enfermedades Autoinmunes/genética , Polimorfismo de Nucleótido Simple , Esclerodermia Sistémica/genética , Adulto , Anciano , Enfermedades Autoinmunes/inmunología , Antígeno CTLA-4 , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Persona de Mediana Edad , Regiones Promotoras Genéticas , Esclerodermia Sistémica/inmunología

Asunto(s)

Ciclosporina/uso terapéutico , Inmunosupresores/uso terapéutico , Complicaciones del Embarazo/tratamiento farmacológico , Esclerodermia Sistémica/tratamiento farmacológico , Adulto , Femenino , Humanos , Embarazo , Resultado del Embarazo

RESUMEN

INTRODUCTION: The aim of the present study was to demonstrate, by nailfold videocapillaroscopy (NVC), the existence of diagnostic and follow-up parameters of microvascular damage in systemic sclerosis (SS) (grouped in the "early", "active" and "late" NVC patterns). The presence of the different subsets of skin involvement (limSS and difSS), as well as the role of some specific serum autoantibodies in the expression of the NVC parameters were investigated. METHODS: 245 consecutive SS patients were recruited and clinical data assessed. Antinuclear (ANA), antitopoisomerase I (Scl70) and anticentromere (ACA) antibodies were investigated in all patients. RESULTS: Giant capillaries and hemorrhages were confirmed to be the earliest NVC finding in SS (diagnostic parameters). The loss of capillaries, along with ramified capillaries and vascular architectural disorganization were validated as parameters of progression of SS microangiopathy. Really, both Raynaud's phenomenon (RP) and SS duration were detected longer in patients with the "late" than in those with the "active" or the "early" NVC pattern. Patients affected by limSS were found to have shorter disease duration, as well as showed more frequently the "early" or the "active" NVC patterns. Conversely, patients affected by the difSS showed longer disease duration and mostly the presence of the "active" or "late" NVC pattern. The Scl70 positivity was lower in the patients showing the "early" than in those with the "active" and the "late" NVC patterns, whereas no significant correlation was found between the Scl70 presence and both RP and SS duration. The ACA positivity was higher in patients showing the "early" NVC pattern, as well as in patients with longer disease duration. CONCLUSIONS: This study confirms that the identification of distinct NVC patterns may be useful to evaluate the severity and the stage of the SS microvascular damage. The presence of the Scl70 antibodies seems related to a more rapid progression of the SS microangiopathy. On the contrary, the presence of the ACA seems to be related to a slower progression of the SS microvascular damage. The SS peripheral microangiopathy is similar as in patients with limSS, as in those affected by difSS.

Asunto(s)

Angioscopía Microscópica , Esclerodermia Sistémica/patología , Autoanticuerpos/sangre , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Uñas , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/complicaciones , Enfermedades de la Piel/etiología , Grabación en Video

Asunto(s)

Circulación Coronaria , Enfermedad Coronaria/fisiopatología , Esclerodermia Sistémica/fisiopatología , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Enfermedad Coronaria/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Flujo Sanguíneo Regional , Esclerodermia Sistémica/sangre

RESUMEN

OBJECTIVES: We investigated whether the non-invasive determination of coronary flow reserve (CFR), as evaluated by transthoracic Doppler echocardiography, might be a potential method to detect early dysfunction of cardiovascular system in patients affected by systemic sclerosis (SSc) without clinical signs or symptoms of cardiac impairment. The possible correlations between the CFR values and the duration of the disease, specific autoantibodies and cutaneous involvement subsets were investigated. METHODS: Forty-four consecutive patients affected by SSc were analysed. The CFR was detected in the distal left anterior descending coronary artery by contrast-enhanced transthoracic second harmonic Doppler in all SSc patients and in 16 healthy controls. CFR was assessed at rest and during hyperaemia induced by administration of adenosine at 0.14 mg/kg/min over 5 min. The CFR was calculated as the ratio between hyperaemic (peak adenosine infusion) and resting peak diastolic velocity (PdvCFR) and resting velocity time integral (VtiCFR). Past medical history was carefully investigated. RESULTS: Both PdvCFR and VtiCFR were significantly reduced in SSc patients when compared with controls (P<0.0001). In particular, both PdvCFR and VtiCFR were significantly lower in patients with dSSc when compared with patients affected by lSSc (P<0.02 and P<0.04 respectively). No statistically significant correlation was found between CFR values and history of smoking, serum levels of cholesterol or triglycerides, blood pressure, age of patients, duration of SSc and serum autoantibody positivity for ANA, ACA and Scl70. CONCLUSIONS: CFR is often reduced in SSc patients. CFR was lower in patients with dSSc than in those affected by lSSc. A reduced CFR value should be considered an indirect sign of heart involvement in scleroderma, but its clinical and prognostic implications need to be clarified.

Asunto(s)

Circulación Coronaria , Esclerodermia Sistémica/fisiopatología , Adulto , Anciano , Autoanticuerpos/sangre , Velocidad del Flujo Sanguíneo , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiopatología , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerodermia Sistémica/diagnóstico por imagen

RESUMEN

BACKGROUND: The immunomodulatory effects of allogeneic blood transfusion may contribute to a poor prognosis in patients with cancer who are undergoing surgery, and clinical trials have been carried out to investigate whether these patients would benefit from autologous blood donation. As the immunomodulatory effects of allogeneic blood transfusion have been related to soluble molecules released from residual WBCs during storage, the in vitro immunomodulatory activity of soluble molecules detected in supernatants from stored autologous blood was evaluated. STUDY DESIGN AND METHODS: Blood was donated by four healthy volunteers. Packed WBC-reduced RBCs were obtained and stored for 30 days, and supernatants were collected. FFP and serum were also obtained. The concentration of soluble molecules was determined by immunoenzymatic assays. The in vitro immunomodulatory activity of undiluted blood component supernatant was assessed by antigen-specific cytotoxic T-cell activity and mixed lymphocyte reactions in autologous combinations and by apoptosis induction in Fas+ cells. RESULTS: The concentrations of soluble Fas-ligand and HLA class I molecules were higher in packed RBCs than in WBC-reduced RBCs, FFP, and serum. Undiluted supernatants of packed RBCs strongly inhibited functional assays and induced apoptosis in Fas+ cells. The immunomodulatory effects were correlated with the amount of soluble Fas ligand and HLA class I molecules. CONCLUSION: The results of the present study are comparable with those already reported in allogeneic blood components, and they indicate that undiluted supernatants of autologous blood components may exert immunosuppressive effects in vitro.

Asunto(s)

Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase I/farmacología , Glicoproteínas de Membrana/inmunología , Glicoproteínas de Membrana/farmacología , Adulto , Apoptosis/efectos de los fármacos , Transfusión de Sangre Autóloga , Pruebas Inmunológicas de Citotoxicidad , Transfusión de Eritrocitos , Eritrocitos/inmunología , Eritrocitos/metabolismo , Proteína Ligando Fas , Antígenos de Histocompatibilidad Clase I/sangre , Humanos , Cadenas Pesadas de Inmunoglobulina/análisis , Cadenas Pesadas de Inmunoglobulina/inmunología , Cadenas Pesadas de Inmunoglobulina/farmacología , Inmunosupresores/sangre , Inmunosupresores/inmunología , Inmunosupresores/farmacología , Células Jurkat , Leucaféresis , Prueba de Cultivo Mixto de Linfocitos , Glicoproteínas de Membrana/sangre , Solubilidad , Microglobulina beta-2/análisis , Microglobulina beta-2/inmunología , Microglobulina beta-2/farmacología

RESUMEN

Alteration of T cell suppression function has been recognized in patients with systemic lupus erythematosus (SLE). Recently, CD8(+) T suppressor lymphocytes (CD8(+) Ts) have been generated in vitro by incubating purified CD8(+) T cells with IL-2 and GM-CSF. Using this method, we generated CD8(+) Ts from patients affected by SLE. No major differences were found in the CD8(+) Ts phenotype between SLE patients and healthy subjects. CD8(+) Ts from SLE patients with active disease did not inhibit the anti-CD3 mAb-induced proliferation of autologous PBMC, whereas CD8(+) Ts from SLE patients in remission exerted an inhibitory activity comparable to normal subjects. The inhibitory effect of CD8(+) Ts cells was neither mediated by cytotoxic activity nor by apoptosis induction. Two cytokines, IFN-gamma and IL-6, were found to be responsible for the function of CD8(+) TS: In fact, counteraction of CD8(+) Ts suppression activity was obtained by blocking IFN-gamma with a specific Ab or by inhibiting CD8(+) Ts-mediated IL-6 secretion by an antisense oligonucleotide. Interestingly, CD8(+) Ts from SLE patients showed a peculiar cytokine pattern characterized by an impaired secretion of IL-6 and an increased secretion of IL-12. Thus, it appears that an altered balance between inhibitory (IL-6) and stimulatory (IL-12) cytokines might be responsible for the functional impairment of CD8(+) Ts in SLE patients.

Asunto(s)

Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/patología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/patología , Adulto , Anticuerpos Monoclonales/farmacología , Complejo CD3/inmunología , Sistema Libre de Células/inmunología , Células Cultivadas , Técnicas de Cocultivo , Citocinas/biosíntesis , Regulación hacia Abajo/inmunología , Femenino , Humanos , Inmunofenotipificación , Interleucina-12/biosíntesis , Interleucina-6/antagonistas & inhibidores , Interleucina-6/biosíntesis , Células K562 , Leucocitos Mononucleares/inmunología , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Solubilidad , Factores Supresores Inmunológicos/fisiología , Linfocitos T Reguladores/metabolismo , Regulación hacia Arriba/inmunología

Asunto(s)

Adyuvantes Inmunológicos/fisiología , Transfusión Sanguínea , Glicoproteínas de Membrana/fisiología , Receptor fas/fisiología , Proteína Ligando Fas , Humanos

RESUMEN

It has been known for many years that blood transfusions may have immunomodulatory effects, however an ultimate explanation of this phenomenon is lacking. In the present paper we report that the concentrations of soluble HLA class I (sHLA-I) and soluble Fas ligand (sFasL) molecules in supernatants of blood components which contain elevated numbers of residual donor leukocytes, like red blood cells and random-donor platelets, are significantly higher than in other blood components. Elevated amounts of sFasL molecules are also found in some commercial immunoglobulin preparations. sHLA-I and sFasL molecules in blood components and in immunoglobulin preparations are biologically active in vitro as they inhibit mixed lymphocyte responses and cytotoxic T cell activity in allogeneic and autologous combinations and induce apoptosis in Fas-positive cells. If these results are paralleled in vivo the amount of sHLA-I and sFasL molecules should be taken into account in clinical practice in order to select the blood component and the immunoglobulin preparation which could induce the desired immunomodulatory effect in the recipient.

Asunto(s)

Transfusión Sanguínea , Antígenos HLA/sangre , Tolerancia Inmunológica/inmunología , Glicoproteínas de Membrana/sangre , Adyuvantes Inmunológicos/sangre , Animales , Proteína Ligando Fas , Genes MHC Clase I , Antígenos HLA/inmunología , Antígenos HLA/fisiología , Humanos , Tolerancia Inmunológica/efectos de los fármacos , Glicoproteínas de Membrana/inmunología , Glicoproteínas de Membrana/fisiología

RESUMEN

Besides being present in serum in association with beta2-mu, HLA class I heavy chains are also present in serum as beta2-micro-free moieties. The increase in serum levels of beta2-micro-associated HLA class I heavy chains in conditions associated with an activation of the immune system have prompted us to measure the serum levels of beta2-mu-free HLA class I heavy chains in the course of immune responses to viral antigens and to mismatched histocompatibility antigens. The serum level of beta2-mu-free HLA class I heavy chains, like that of beta2-mu-associated HLA class I heavy chains was significantly increased in patients affected by advanced HIV-1 infection or by chronic hepatitis C (CHC). In the latter group of patients an association was found between a reduction in the beta2-mu-free HLA class I heavy chain serum level and response to therapy with interferon alpha and ribavirin. Moreover, the beta2-mu-free HLA class I heavy chain serum level was increased more than that of beta2-mu-associated HLA class I heavy chains during episodes of liver ischemia following liver transplantation and in the course of acute graft rejection and of acute graft-versus-host-disease (GVHD) after allogeneic bone marrow transplantation (BMT). These results suggest that the serum levels of beta2-mu-free and beta2-mu-associated HLA class I heavy chains are independently regulated. Furthermore, beta2-mu-free HLA class I heavy chain serum level may be a useful marker to monitor response to therapy in CHC patients and the clinical course of liver and bone marrow grafts.

Asunto(s)

Antígenos VIH/inmunología , Infecciones por VIH/inmunología , VIH-1 , Antígenos HLA/sangre , Antígenos de Histocompatibilidad Clase I/sangre , Microglobulina beta-2/sangre , Adulto , Anciano , Fármacos Anti-VIH/uso terapéutico , Trasplante de Médula Ósea/inmunología , Citometría de Flujo , Rechazo de Injerto/inmunología , Enfermedad Injerto contra Huésped/inmunología , Antígenos HLA/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Trasplante de Hígado/inmunología , Persona de Mediana Edad , Microglobulina beta-2/inmunología

RESUMEN

Allogeneic blood transfusions may have immunomodulatory effects including improved allograft acceptance and increased risk for cancer recurrence or post-operative bacterial infections. These effects are associated with the presence of leukocytes in transfused blood and are reduced by pre-storage leuko-reduction. However, the precise mechanism of this effect has not yet been elucidated. We report that the concentrations of soluble major histocompatibility complex class I and soluble Fas-ligand molecules are significantly higher in supernatants of blood components containing elevated numbers of residual donor leukocytes, such as red blood cells and random-donor platelets, than in other blood components. Elevated amounts of soluble Fas-ligand molecules are also found in some intravenous immunoglobulin preparations. Soluble molecules detected in blood components and in immunoglobulin preparations are biologically active in vitro. In fact, they inhibit mixed lymphocyte responses and cytotoxic T cell activity in allogeneic and autologous combinations and induce apoptosis in Fas-positive cells. These results should be taken into account in clinical practice to select the blood component or the immunoglobulin preparation in order to induce or prevent an immunosuppressive effect in the recipient.

Asunto(s)

Adyuvantes Inmunológicos/uso terapéutico , Transfusión Sanguínea , Inmunoglobulinas Intravenosas/inmunología , Complejo Mayor de Histocompatibilidad/inmunología , Receptor fas/inmunología , Antígenos HLA/inmunología , Humanos , Leucocitos/inmunología , Ligandos , Solubilidad

RESUMEN

In the present study, we have evaluated the apoptotic effect of soluble human MHC class I (sHLA-I) antigens on CD8(+) T lymphocytes. sHLA-I antigens and beta(2)-microglobulin-free HLA class I heavy chains, isolated from serum, induced apoptosis on phytohemagglutinin-activated CD8(+) T lymphocytes in autologous and allogeneic combinations. The extent of CD8(+) T cell apoptosis depends on the degree of activation, time of incubation with sHLA-I antigens and amount of sHLA-I antigens added to the cultures. Apoptosis is induced by the interaction of Fas (CD95)(+) cells with soluble Fas ligand which is released following binding of sHLA-I antigens to CD8 molecules. These results suggest that sHLA-I antigens may regulate immune responses by inducing apoptosis in activated CD8(+) T cells.

Asunto(s)

Apoptosis , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Antígenos de Histocompatibilidad Clase I/metabolismo , Activación de Linfocitos , Receptor fas/metabolismo , Electroforesis en Gel de Poliacrilamida , Citometría de Flujo , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Inmunoensayo , Ligandos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Solubilidad , Receptor fas/inmunología

RESUMEN

BACKGROUND: sHLA molecules are the soluble forms of their membrane bound counterparts. sHLA class I. were recently reported to be a useful marker in the prediction of graft versus host reaction (GVHR) in adults. To confirm these presumptions in children we measured sHLA class I. serum levels in children after allogeneic bone marrow transplantation (BMT). We also investigated the levels of sHLA in the supernatants of mixed lymphocyte cultures (MLC) as possible predictors of GVHR prior to BMT. METHODS AND RESULTS: Group of 6 investigated children included 1 child with severe combined immunodeficiency, 3 children with acute lymphoblastic leukemia, 1 with severe combined immunodeficiency, 3 children with acute lymphoblastic leukemia, 1 with severe aplastic anemia and 1 with non Hodgkin lymphoma. The period of follow up varied from 15 days to 21 months according to the course of the disease. In the prediction of GVHR the levels of sHLA were measured in 5 children with acute leukemia in supernatants of MLC and the results were compared with the grade of GVHR classified according Seattle criteria. Soluble HLA class I. molecules were evaluated by ELISA. Rise of the levels of sHLA preceded 1-2 days the clinical signs of GVHR, however, it could not be distinguished from the occasional rise of a different cause. The levels of sHLA found in the supernatants of MLC showed individual results, which did not correspond to the level of cytokines in the same culture, or to the grade of GVHR observed. However, twice higher levels of sHLA in the culture of donor lymphocytes correlated with the lethal outcome of GVHR despite the fact that the donors were HLA identical siblings. CONCLUSIONS: The usefulness of sHLA levels as the predictors of GVHR has to be interpreted with great caution, but they can be used as a part of the mosaic composed of the clinical image and other laboratory results indicating GVHR. The predictive value of sHLA in supernatants of MLC is still to be evaluated.

Asunto(s)

Trasplante de Médula Ósea/efectos adversos , Enfermedad Injerto contra Huésped/diagnóstico , Antígenos de Histocompatibilidad Clase I/sangre , Adolescente , Biomarcadores/sangre , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Prueba de Cultivo Mixto de Linfocitos , Masculino , Valor Predictivo de las Pruebas , Solubilidad

RESUMEN

The authors describe a clinical case of an HIV+, HBV+ and HCV+ 46-year-old male patient, with a history of drug abuse of intravenous heroin, admitted to their attention for high remittent fever (39 C), weight loss and severe dysphonia. The increasing severity of dysphonia had required a fiberlaryngoscopic examination which allowed a diagnosis of hypertrophy of vocal chords. The Wright-Giemsa stain performed on vocal chord biopsy evidenced Leishmania infantum. The same protozoon was subsequently also revealed in bone marrow aspirate. The patient underwent a course of therapy with Amphotericin B deoxycolate (0.5 mg/kg) which had to be interrupted due to insurgence of diffuse petechiae and switched to Amphotericin in cholesterinic suspension (2.5 mg/kg every 21 days). After three months, insurgence of high fever related to the infusion induced the start of therapy with liposomal Amphotericin B (3 mg/kg every 28 days) which led in 4 weeks to a complete clinical remission. Prophylaxis with liposomal Amphotericin B is continuing and remission has persisted for 40 months. This case report shows the importance of liposomal Amphotericin B therapy in order either to obtain clinical remission of visceral leishmaniasis or, in secondary prophylaxis, to reduce the risk of the disease's recurrence.