RESUMEN
BACKGROUND: Gamma-heavy chain disease is a rare disease, described so far in approximately 150 cases. The aim of this work was laboratory dia-gnostics of immunoglobulin heavy chain disease. MATERIALS AND METHODS: A 60-year-old patient was referred to the University Hospital in Ostrava for suspected marginal zone lymphoma from gastric bio-psy. Staging examinations including bone marrow trepanobio-psy and PET/CT were added; special examinations required serum protein electrophoresis, immunofixation electrophoresis, determination of polyclonal immunoglobulins, free light chains, and immunoglobulin heavy/light chain pairs. Isoelectric focusing in agarose gel followed by affinity immunoblotting and SDS electrophoresis was added due to unclear findings. RESULTS: 0.1 % of plasma cells were found in the bone marrow, of which 87 % were clonal (pathological) plasma cells, followed by the cyt cytotype LAMBDA + CD38 + CD138 + CD45 + CD19 + CD56- CD27 + CD81- CD117-. Monoclonal heavy chains were found in the patients serum. No monoclonal immunoglobulin heavy or light chains were detected in urine. The PET/CT examination showed generalized lymphadenopathy, splenomegaly and inhomogeneous accumulation of fluorodeoxyglucose in axillary and appendicular skeleton, but without the presence of typical osteolytic lesions. CONCLUSION: Monoclonal heavy chains of immunoglobulins are a rare disease. In contrast to the detection of a complete paraprotein molecule, additional methods must be used to confirm them. The finding of monoclonal heavy chain gamma in the serum of the study patient is related to the presence of marginal zone lymphoma, which was proven from a gastric bio-psy. The study was supported by the project of MH CZ - DRO - FNOs /2017 (Biobank in Teaching Hospital Ostrava) The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Asunto(s)
Enfermedad de las Cadenas Pesadas/diagnóstico , Cadenas gamma de Inmunoglobulina/sangre , Enfermedad de las Cadenas Pesadas/sangre , Humanos , Masculino , Persona de Mediana Edad , PronósticoAsunto(s)
Xantogranuloma Necrobiótico/diagnóstico , Paraproteinemias/diagnóstico , Administración Intravenosa , Adulto , Biopsia , Sedimentación Sanguínea , Médula Ósea/patología , Ciclofosfamida/administración & dosificación , Párpados , Femenino , Humanos , Cadenas gamma de Inmunoglobulina/sangre , Inmunoglobulinas Intravenosas/administración & dosificación , Xantogranuloma Necrobiótico/sangre , Xantogranuloma Necrobiótico/tratamiento farmacológico , Xantogranuloma Necrobiótico/etiología , Paraproteinemias/sangre , Paraproteinemias/complicaciones , Paraproteinemias/tratamiento farmacológico , Piel/patologíaAsunto(s)
Anticuerpos Monoclonales/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/antagonistas & inhibidores , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Paraproteinemias/diagnóstico , Paraproteinemias/inmunología , Proteinosis Alveolar Pulmonar/tratamiento farmacológico , Anticuerpos Monoclonales/sangre , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Biopsia , Médula Ósea/patología , Cromatografía Liquida , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Cadenas gamma de Inmunoglobulina/sangre , Cadenas gamma de Inmunoglobulina/inmunología , Masculino , Gammopatía Monoclonal de Relevancia Indeterminada/sangre , Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico , Gammopatía Monoclonal de Relevancia Indeterminada/inmunología , Paraproteinemias/sangre , Proteinosis Alveolar Pulmonar/diagnóstico , Proteinosis Alveolar Pulmonar/etiología , Espectrometría de Masas en Tándem , Tomografía Computarizada por Rayos XAsunto(s)
Anticuerpos Monoclonales/uso terapéutico , Electroforesis de las Proteínas Sanguíneas/métodos , Cadenas gamma de Inmunoglobulina/sangre , Cadenas kappa de Inmunoglobulina/sangre , Mieloma Múltiple/tratamiento farmacológico , Paraproteínas/análisis , Artefactos , Humanos , Cadenas gamma de Inmunoglobulina/análisis , Estudios RetrospectivosRESUMEN
RATIONALE: The aim of the study was to use a technique that combines acid hydrolysis and matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF MS) in order to detect the serum biomarkers of patients diagnosed with schizophrenia both before and after four-week antipsychotic treatment with risperidone. METHODS: During this study's two-year period, inpatients were diagnosed with schizophrenia using the Structured Clinical Interview for DSM-IV Axis I Disorders. Severity was then evaluated using the Positive and Negative Syndrome Scale both at baseline and at endpoint following four-week treatment with risperidone. The patients' serum biomarkers were quickly measured using acid hydrolysis and MALDI-TOF MS. The resulting peptides were then analyzed using MALDI-TOF MS. We constructed a receiver operating characteristic (ROC) curve for the evaluated biomarkers. RESULTS: We recruited 20 pairs of participants for this study. The experimental group was treated with serum protein with HCl for 10 minutes to effectively hydrolyze abundant proteins. The target peptide, the immunoglobulin gamma chain (IgG), was then rapidly detected using this manner. A significant difference was found in the IgG levels of patients with schizophrenia before and after antipsychotic treatment. We constructed a ROC curve based on the IgG, and the area under said curve was 0.969. In comparison to conventional detection protocols, this method takes only minutes to complete and is also less costly. CONCLUSIONS: This study found that applying acid hydrolysis with MALDI-TOF MS technology could rapidly differentiate serum IgG levels in patients with schizophrenia before and after being treated with risperidone. This IgG difference may enhance the understanding of mechanism of antipsychotic treatment of schizophrenia. Copyright © 2016 John Wiley & Sons, Ltd.
Asunto(s)
Antipsicóticos/uso terapéutico , Cadenas gamma de Inmunoglobulina/sangre , Risperidona/uso terapéutico , Esquizofrenia/sangre , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Biomarcadores/sangre , Humanos , Esquizofrenia/tratamiento farmacológicoRESUMEN
There are limited data on serum total light chain (sTLC) in lymphoma and its relative role on the outcome of diffuse large B cell lymphoma (DLBCL) patients. Blood samples from 46 cases newly diagnosed with DLBCL were collected consecutively during chemotherapy to detect sTLC, IgG, IgA, and IgM levels. Clinical data and survival outcomes were analyzed according to the results of sTLC measurements. In summary, 22 patients (47.8 %) had abnormal k or λ light chain, respectively, and 6 patients (13.0 %) had both abnormal k and λ light chains before chemotherapy. Patients with elevated k light chain more frequently displayed multiple extra-nodal organ involvement (P = 0.01) and had an inferior overall survival (OS) (P = 0.041) and progression-free survival (PFS) (P = 0.044) compared to patients with normal level of k light chain. Furthermore, patients with elevated level of both k and λ also exhibited significant association with shorter OS (P = 0.002) and PFS (P = 0.009). Both elevated k alone and concurrent elevated k and λ had independent adverse effects on PFS (P = 0.031 and P = 0.019, respectively). sTLC level was reduced gradually by treatment in this study and reached the lowest point after the fourth cycle of chemotherapy, which was consistent with the disease behavior during chemotherapy. Considering the small sample size of this study, these results should be confirmed in a larger prospective study.
Asunto(s)
Cadenas gamma de Inmunoglobulina/sangre , Cadenas kappa de Inmunoglobulina/sangre , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores/sangre , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Rituximab , Vincristina/administración & dosificaciónRESUMEN
Gamma heavy chain disease (gHCD) is a rare lymphoproliferative disorder characterized by the production of a truncated immunoglobulin heavy chain. Although some cases of gHCD are concurrent with other lymphoid neoplasms, few have been reported. We herein present the case of a 73-year-old woman with gHCD and T-cell large granular lymphocytic leukemia. A multiparameter flow cytometry analysis revealed neoplastic cells that were positive for CD28, a marker of T-cell activation, the anti-apoptotic antigen of neoplastic plasma cells, CD38 and CD45. The results of this multiparameter flow cytometry analysis may contribute to furthering the understanding of the clinicopathological features of gHCD.
Asunto(s)
Anemia/inmunología , Fatiga/inmunología , Enfermedad de las Cadenas Pesadas/patología , Cadenas gamma de Inmunoglobulina/metabolismo , Leucemia Linfocítica Granular Grande/patología , Linfocitos/metabolismo , Anciano , Anemia/etiología , Análisis Citogenético , Fatiga/etiología , Femenino , Citometría de Flujo , Enfermedad de las Cadenas Pesadas/complicaciones , Enfermedad de las Cadenas Pesadas/inmunología , Humanos , Cadenas Pesadas de Inmunoglobulina , Cadenas gamma de Inmunoglobulina/sangre , Leucemia Linfocítica Granular Grande/complicaciones , Leucemia Linfocítica Granular Grande/inmunologíaAsunto(s)
Crioglobulinemia/inmunología , Síndrome de Guillain-Barré/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Cadenas gamma de Inmunoglobulina/inmunología , Cadenas kappa de Inmunoglobulina/inmunología , Vasculitis Leucocitoclástica Cutánea/inmunología , Vitíligo/inmunología , Biopsia , Crioglobulinemia/complicaciones , Crioglobulinemia/diagnóstico , Crioglobulinemia/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/tratamiento farmacológico , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Cadenas gamma de Inmunoglobulina/sangre , Cadenas kappa de Inmunoglobulina/sangre , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Vasculitis Leucocitoclástica Cutánea/diagnóstico , Vasculitis Leucocitoclástica Cutánea/tratamiento farmacológico , Vitíligo/diagnóstico , Vitíligo/tratamiento farmacológicoRESUMEN
The common γ-chain (γc) plays a central role in signaling by IL-2 and other γc-dependent cytokines. Here we report that activated T cells produce an alternatively spliced form of γc mRNA that results in protein expression and secretion of the γc extracellular domain. The soluble form of γc (sγc) is present in serum and directly binds to IL-2Rß and IL-7Rα proteins on T cells to inhibit cytokine signaling and promote inflammation. sγc suppressed IL-7 signaling to impair naive T cell survival during homeostasis and exacerbated Th17-cell-mediated inflammation by inhibiting IL-2 signaling upon T cell activation. Reciprocally, the severity of Th17-cell-mediated inflammatory diseases was markedly diminished in mice lacking sγc. Thus, sγc expression is a naturally occurring immunomodulator that regulates γc cytokine signaling and controls T cell activation and differentiation.
Asunto(s)
Empalme Alternativo/inmunología , Encefalomielitis Autoinmune Experimental/inmunología , Cadenas gamma de Inmunoglobulina/inmunología , Inflamación/inmunología , Células Th17/inmunología , Animales , Autoinmunidad , Diferenciación Celular/inmunología , Proliferación Celular , Supervivencia Celular/inmunología , Cadenas gamma de Inmunoglobulina/sangre , Cadenas gamma de Inmunoglobulina/genética , Inmunomodulación , Subunidad beta del Receptor de Interleucina-2/inmunología , Subunidad alfa del Receptor de Interleucina-5/inmunología , Activación de Linfocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Unión Proteica/inmunología , Isoformas de Proteínas/genética , Isoformas de Proteínas/inmunología , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Transducción de Señal/inmunologíaRESUMEN
Gamma heavy-chain disease (gHCD) is defined as a lymphoplasmacytic neoplasm that produces an abnormally truncated immunoglobulin gamma heavy-chain protein that lacks associated light chains. There is scant information in the literature regarding the morphologic findings in this rare disorder, but cases have often been reported to resemble lymphoplasmacytic lymphoma (LPL). To clarify the spectrum of lymphoproliferative disorders that may be associated with gHCD, this study reports the clinical, morphologic, and phenotypic findings in 13 cases of gHCD involving lymph nodes (n=7), spleen (n=2), bone marrow (n=8), or other extranodal tissue biopsies (n=3). Clinically, patients showed a female predominance (85%) with frequent occurrence of autoimmune disease (69%). Histologically, 8 cases (61%) contained a morphologically similar neoplasm of small lymphocytes, plasmacytoid lymphocytes, and plasma cells that was difficult to classify with certainty, whereas the remaining 5 cases (39%) showed the typical features of one of several other well-defined entities in the 2008 WHO classification. This report demonstrates that gHCD is associated with a variety of underlying lymphoproliferative disorders but most often shows features that overlap with cases previously reported as "vaguely nodular, polymorphous" LPL. These findings also provide practical guidance for the routine evaluation of small B-cell neoplasms with plasmacytic differentiation that could represent a heavy-chain disease and give suggestions for an improved approach to the WHO classification of gHCD.
Asunto(s)
Enfermedades Autoinmunes/diagnóstico , Enfermedad de las Cadenas Pesadas/diagnóstico , Cadenas gamma de Inmunoglobulina/sangre , Tejido Linfoide/patología , Linfoma de Células B/diagnóstico , Macroglobulinemia de Waldenström/diagnóstico , Adulto , Anciano , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/metabolismo , Biomarcadores de Tumor/metabolismo , Células Clonales , Comorbilidad , Análisis Citogenético , Femenino , Enfermedad de las Cadenas Pesadas/sangre , Enfermedad de las Cadenas Pesadas/epidemiología , Enfermedad de las Cadenas Pesadas/genética , Humanos , Cadenas gamma de Inmunoglobulina/genética , Inmunofenotipificación , Hibridación Fluorescente in Situ , Linfocitos/metabolismo , Linfocitos/patología , Tejido Linfoide/metabolismo , Linfoma de Células B/epidemiología , Linfoma de Células B/genética , Linfoma de Células B/metabolismo , Masculino , Persona de Mediana Edad , Células Plasmáticas/metabolismo , Células Plasmáticas/patología , Factores Sexuales , Reino Unido/epidemiología , Estados Unidos/epidemiología , Macroglobulinemia de Waldenström/epidemiología , Macroglobulinemia de Waldenström/genética , Macroglobulinemia de Waldenström/metabolismoAsunto(s)
beta-Globulinas/análisis , Enfermedad de las Cadenas Pesadas/diagnóstico , Cadenas gamma de Inmunoglobulina/sangre , Anciano de 80 o más Años , Electroforesis de las Proteínas Sanguíneas , Neoplasias Óseas/complicaciones , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/secundario , Diagnóstico Diferencial , Reacciones Falso Positivas , Fracturas del Cuello Femoral/etiología , Enfermedad de las Cadenas Pesadas/sangre , Enfermedad de las Cadenas Pesadas/orina , Humanos , Inmunoelectroforesis , Inmunoglobulina G/sangre , Inmunoglobulina G/orina , Cadenas Ligeras de Inmunoglobulina/sangre , Cadenas Ligeras de Inmunoglobulina/orina , Masculino , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patologíaAsunto(s)
beta-Globulinas/análisis , Enfermedad de las Cadenas Pesadas/diagnóstico , Cadenas gamma de Inmunoglobulina/sangre , Electroforesis de las Proteínas Sanguíneas , Reacciones Falso Positivas , Enfermedad de las Cadenas Pesadas/sangre , Enfermedad de las Cadenas Pesadas/orina , Humanos , Inmunoelectroforesis , Cadenas Ligeras de Inmunoglobulina/sangre , Cadenas Ligeras de Inmunoglobulina/orinaAsunto(s)
beta-Globulinas/análisis , Enfermedad de las Cadenas Pesadas/diagnóstico , Cadenas gamma de Inmunoglobulina/sangre , Albuminuria/diagnóstico , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/secundario , Diagnóstico Diferencial , Reacciones Falso Positivas , Enfermedad de las Cadenas Pesadas/sangre , Enfermedad de las Cadenas Pesadas/orina , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/orina , Cadenas kappa de Inmunoglobulina/sangre , Cadenas kappa de Inmunoglobulina/orina , Masculino , Mieloma Múltiple/diagnóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patologíaRESUMEN
Heavy chain diseases (HCDs) are rare B-cell lymphoproliferative neoplasias characterized by the production of a monoclonal component consisting of a truncated monoclonal Ig heavy chain without the associated light chain. Among them, patients with gamma-HCD are so rare that no more than 150 cases can be found in the literature. In this paper, we report one additional case: an 83-year-old man with a gamma-HCD, in whom a kappa light chain component was detected in the serum by using the serum free light-chain assessment and in addition monoclonal kappa cytoplasmic expression was detected in bone marrow plasma cells by flow cytometric analysis. In the work-up of the patient, the underlying anatomopathological lymphoproliferative disease corresponded to a lymphoplasmacytic lymphoma, as it is stated in the current World Health Organization classification (2008), with both lymphadenopathic and bone marrow infiltration. As in other cases, several autoimmune manifestations (antiphospholipidic syndrome and immune thrombocytopenia) were present during the course of the disease in this patient. This case report illustrates a new case of gamma-HCD, in which serum free light-chain analysis and flow cytometry represented a valuable tool for diagnosis, a finding that could be very important for the future management of these patients.
Asunto(s)
Enfermedad de las Cadenas Pesadas/sangre , Enfermedad de las Cadenas Pesadas/diagnóstico , Cadenas gamma de Inmunoglobulina/sangre , Anciano de 80 o más Años , Citometría de Flujo , Humanos , MasculinoRESUMEN
We describe the case of a 34-year-old gentleman investigated for persistent neutropaenia following two episodes of pneumonia. Specialist investigations led to the diagnosis of multiple myeloma (MM) producing a truncated monoclonal gamma(3) heavy chain (HC) immunoglobulin molecule unattached to a light chain (LC) with atypical features for both MM and HC disease. Western blot showed gamma(3)HC was truncated with a large deletion (75 kDa). Flow cytometry of the bone marrow aspirate revealed an unusual staining pattern. This plasma cell dyscrasia was also unusual in that a subpopulation (30%) secreted large quantities of free LC (FLC) as well as truncated IgG HC. This is the first description, investigation and treatment of MM with a plasma cell population producing truncated gamma(3)HC and kappaFLC M-proteins and illustrates a number of unique immunological and clinical features.
Asunto(s)
Cadenas gamma de Inmunoglobulina/sangre , Cadenas kappa de Inmunoglobulina/sangre , Mieloma Múltiple/inmunología , Adulto , Humanos , Cadenas gamma de Inmunoglobulina/química , Cadenas kappa de Inmunoglobulina/química , Masculino , Mieloma Múltiple/sangre , Mieloma Múltiple/terapia , Trasplante de Células Madre de Sangre Periférica , Resultado del TratamientoRESUMEN
BACKGROUND: The integrin alpha(IIb)beta(3) is the major mediator of platelet aggregation and has, therefore, become an important target of antithrombotic therapy. Antagonists of alpha(IIb)beta(3), for example abciximab, tirofiban and eptifibatide, are used in the treatment of acute coronary syndromes. However, in addition to effective blockade of the integrin, binding of can induce conformational changes in the integrin and can also induce integrin clustering. This class effect of RGD-ligand mimetics might, therefore, underlie paradoxical platelet activation and thrombosis previously reported. OBJECTIVES: To examine the components of signaling pathways and functional responses in platelets that may underlie this phenomenon of paradoxical platelet activation. METHODS: We assessed the effect of lotrafiban, and other alpha(IIb)beta(3) antagonists including the clinically used drug tirofiban, on tyrosine phosphorylation of key signaling proteins in platelets by immunoblotting and also platelet functional outputs such as cytosolic calcium responses, phosphatidylserine exposure (pro-coagulant activity) and dense granule release. RESULTS: In all cases, no effect of alpha(IIb)beta(3) antagonists were observed on their own, but these integrin antagonists did lead to a marked potentiation of glycoprotein VI (GPVI)-associated FcR gamma-chain phosphorylation, activation of Src family kinases and Syk kinase. This correlated with increased dense granule secretion, cytosolic calcium response and exposure of phosphatidylserine on the platelet surface. P2Y(12) antagonism abolished the potentiated phosphatidylserine exposure and dense granule secretion but not the cytosolic calcium response. CONCLUSIONS: These data provide a mechanism for enhancement of platelet activity by alpha(IIb)beta(3) inhibitors, but also reveal a potentially important signaling pathway operating from the integrin to GPVI signaling.
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Biomimética , Plaquetas/efectos de los fármacos , Oligopéptidos/sangre , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Glicoproteínas de Membrana Plaquetaria/metabolismo , Benzodiazepinas/farmacología , Coagulación Sanguínea/efectos de los fármacos , Plaquetas/metabolismo , Señalización del Calcio/efectos de los fármacos , Activación Enzimática , Humanos , Cadenas gamma de Inmunoglobulina/sangre , Péptidos y Proteínas de Señalización Intracelular/sangre , Ligandos , Fosfatidilserinas/sangre , Fosforilación , Piperidinas/farmacología , Inhibidores de Agregación Plaquetaria/efectos adversos , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/química , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo , Conformación Proteica , Proteínas Tirosina Quinasas/sangre , Antagonistas del Receptor Purinérgico P2 , Receptores Purinérgicos P2/sangre , Receptores Purinérgicos P2Y12 , Vesículas Secretoras/efectos de los fármacos , Vesículas Secretoras/metabolismo , Quinasa Syk , Factores de Tiempo , Tirofibán , Tirosina/análogos & derivados , Tirosina/sangre , Tirosina/farmacología , Familia-src Quinasas/sangreRESUMEN
AIM: To detect and evaluate the antibodies against Helicobacter pylori (H pylori) neutrophil-activating protein (HP-NAP) in patients with gastric cancer and other gastroduodenal diseases. METHODS: Recombinant HP-NAP was prepared from a prokaryotic expression system in Escherichia coli. Serum positivity and level of HP-NAP-specific antibodies in sera from 43 patients with gastric cancer, 28 with chronic gastritis, 28 with peptic ulcer, and 89 healthy controls were measured by rHP-NAP-based ELISA. rHP-NAP-stimulated production of interleukin-8 (IL-8) and growth-related oncogene (GRO(alpha)) cytokines in the culture supernatant of SGC7901 gastric epithelial cells was also detected. RESULTS: The serum positivity and mean absorbance value of HP-NAP-specific antibodies in the gastric cancer group (97.7% and 1.01 +/- 0.24) were significantly higher than those in the chronic gastritis group (85.7% and 0.89 +/- 0.14, P < 0.005) and healthy control group (27.7% and 0.65 +/- 0.18, P < 0.001). The sensitivity and specificity of ELISA for the detection of HP-NAP-specific antibodies were 95.5% and 91.5%, respectively. HP-NAP could slightly up-regulate IL-8 production in gastric epithelial cell lines but had no effect on GRO(alpha) production. CONCLUSION: Infection with virulent H pylori strains secreting HP-NAP is associated with severe gastroduodenal diseases, and HP-NAP may play a role in the development of gastric carcinoma. rHP-NAP-based ELISA can be used as a new method to detect H pylori infection. The direct effect of HP-NAP on gastric epithelial cells may be limited, but HP-NAP may contribute to inflammatory response or carcinogenesis by activating neutrophils.
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Anticuerpos Antibacterianos/sangre , Proteínas Bacterianas/metabolismo , Helicobacter pylori/inmunología , Neoplasias Gástricas/inmunología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Línea Celular , Quimiocina CXCL1/biosíntesis , Clonación Molecular , ADN Bacteriano/genética , Ensayo de Inmunoadsorción Enzimática , Células Epiteliales/metabolismo , Escherichia coli/metabolismo , Gastritis/inmunología , Helicobacter pylori/genética , Humanos , Cadenas gamma de Inmunoglobulina/sangre , Interleucina-8/biosíntesis , Persona de Mediana Edad , Datos de Secuencia Molecular , Úlcera Péptica/inmunología , Reacción en Cadena de la Polimerasa , Proteínas Recombinantes/biosíntesis , Adulto JovenRESUMEN
Erythropoietin (Epo) is the main erythropoietic hormone. Recombinant human Epo (rHuEpo) is thus used in clinical practice for the treatment of anemia. Accumulating data reveals that Epo exerts pleiotropic activities. We have previously shown an anti-neoplastic activity of Epo in murine multiple myeloma (MM) models, and in MM patients. Our findings that this anti-neoplastic effect operates via CD8+ T lymphocytes led us to hypothesize that Epo possesses a wider range of immunomodulatory functions. Here we demonstrate the effect of Epo on B lymphocyte responses, focusing on three experimental models: (i) tumor-bearing mice, (5T2 MM mouse); (ii) antigen-injected healthy mice; and (iii) antigen-injected transgenic mice (tg6), overexpressing human Epo. In the MM model, despite bone marrow dysfunction, Epo-treated mice retained higher levels of endogenous polyclonal immunoglobulins, compared to their untreated controls. In both Epo-treated wild type and tg6 mice, Epo effect was manifested in the higher levels of splenocyte proliferative response induced in vitro by lipopolysaccharide. Furthermore, these mice had increased in vivo production of anti-dinitrophenyl (DNP) antibodies following immunization with DNP-keyhole limpet hemocyanin. Epo-treated mice showed an enhanced immune response also to the clinically relevant hepatitis B surface antigen. These findings suggest a potential novel use of rHuEpo as an immunomodulator.