RESUMEN
CD1d-restricted invariant natural killer T (iNK T) cells activated by their experimental ligand alpha-galactosylceramide (alpha-GC) can produce both T helper 1 (Th1) and Th2 cytokines and display regulatory functions. Recent studies identified CD4(+) and CD4(-) CD8(-) double-negative (DN) iNK T cells as the two major components of the human population and suggest that they display a Th2 and a Th1 profile, respectively. We compared the Th2-promoting activity of freshly isolated human CD4(+) and DN iNK T cells in terms of their capacity to induce Ig production by autologous B cells. Secretion of IgG and IgE but not IgM was enhanced by the CD4(+) T cell subset (including iNK T cells) but not by its DN counterpart. iNK T cells were directly responsible for this pro-Th2 effect, as demonstrated by the requirement for both alpha-GC stimulation and CD1d presentation, as well as by its disappearance upon iNK T cell depletion. Interaction with iNK T cells led to progressive accumulation of isotype-switched and activated B cells. Myeloid dendritic cells (DC) completely block the induction of Ig production in co-culture. This dominant inhibitory effect of myeloid DC was concomitant with a specific loss of interleukin (IL)-4 production by CD4(+) iNK T but not by conventional T cells. These data support the conclusion that, conversely to the interferon (IFN)-gamma-producing DN human iNK T cell population, interleukin (IL)-4-producing CD4(+) iNK T cells can activate and help B cells to produce both IgG and IgE through a CD1d-dependent mechanism, in keeping with a functional Th1/Th2 dichotomy between these subsets.
Asunto(s)
Linfocitos B/inmunología , Galactosilceramidas/inmunología , Inmunoglobulina G/biosíntesis , Células Asesinas Naturales/inmunología , Linfocitos T CD4-Positivos/inmunología , Proliferación Celular , Técnicas de Cocultivo , Citocinas/biosíntesis , Células Dendríticas/inmunología , Humanos , Inmunoglobulina E/biosíntesis , Activación de Linfocitos/inmunología , Cooperación Linfocítica/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/análisis , Subgrupos de Linfocitos T/inmunología , Células Th2/inmunologíaRESUMEN
The expression of the apoptosis inducer Fas (CD95/APO-1) surface receptor by human foetal neurons was investigated in vitro and ex vivo. Immunofluorescence studies of brain and spinal cord cells in primary cultures and of cryosections obtained from 9- and 10-week-old human foetuses, respectively, showed that all Fas-expressing cells were motoneurons (5.3 and 4.2% of the neurons in brain or spinal cord cultures, respectively) on the basis of morphology, reactivity with the monoclonal antibody SMI-32, a mostly motoneuronal marker and acetylcholine esterase expression. Fas was undetectable on the other cell types in culture. The ability of Fas to induce apoptosis of cultured cells from both tissues was determined by using the terminal transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) method combined with the same double-staining procedure. Under basal culture conditions, about 9% of cells, all glial fibrillary acidic protein-expressing astrocytes, were apoptotic. After a 48-h incubation with Fas ligand, mean 28.5% of brain motoneurons and 29.4% of spinal motoneurons underwent apoptosis, with an inhibition by Z-IETD-FMK, a caspase-8 inhibitor. Hence, Fas appears to be functional through a caspase-8-dependent pathway in a subpopulation of human foetal motoneurons.
Asunto(s)
Péptidos y Proteínas de Señalización Intracelular , Neuronas Motoras/metabolismo , Receptor fas/metabolismo , Feto Abortado/fisiología , Acetilcolinesterasa/metabolismo , Apoptosis , Astrocitos/metabolismo , Western Blotting/métodos , Encéfalo/citología , Encéfalo/metabolismo , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD , Proteínas Portadoras/farmacología , Células Cultivadas , Interacciones Farmacológicas , Proteína Ligando Fas , Técnica del Anticuerpo Fluorescente/métodos , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Etiquetado Corte-Fin in Situ/métodos , Técnicas In Vitro , Células Jurkat/efectos de los fármacos , Células Jurkat/metabolismo , Glicoproteínas de Membrana/farmacología , Neuronas Motoras/efectos de los fármacos , Proteínas de Neurofilamentos/metabolismo , Médula Espinal/citología , Médula Espinal/metabolismo , Factores de TiempoRESUMEN
Sera from 26% of patients with sporadic amyotrophic lateral sclerosis (ALS) induced in vitro apoptosis of a human neuroblastoma cell line, as detected by two methods, and most contained anti-Fas autoantibodies. In contrast, Alzheimer sera (studied as controls) very rarely induced apoptosis and did not contain detectable anti-Fas antibodies. Soluble Fas-ligand levels in ALS sera were not different from those in normal sera, except for slightly higher levels in a single case. In mixed cultures of rat embryonic brain and spinal cord cells, ALS sera (and agonistic anti-Fas monoclonal antibodies and soluble Fas-ligand) induced the apoptosis of a subpopulation of neurons. These neurons were motoneurons on the basis of staining with the monoclonal antibody SMI 32 and Fas expression was restricted to these SMI 32-positive neurons. These data are compatible with the hypothesis of the participation of an autoimmune mechanism possibly related to anti-Fas autoantibodies in certain ALS patients.
Asunto(s)
Esclerosis Amiotrófica Lateral/inmunología , Apoptosis/inmunología , Neuronas Motoras/citología , Neuronas Motoras/inmunología , Receptor fas/inmunología , Animales , Anticuerpos Monoclonales/farmacología , Apoptosis/efectos de los fármacos , Autoanticuerpos/análisis , Autoanticuerpos/farmacología , Western Blotting , Caspasa 3 , Caspasa 8 , Caspasa 9 , Inhibidores de Caspasas , Sistema Nervioso Central/citología , Inhibidores Enzimáticos/farmacología , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Sueros Inmunes/farmacología , Etiquetado Corte-Fin in Situ , Técnicas In Vitro , Células Jurkat , Masculino , Persona de Mediana Edad , Neuroblastoma , Ratas , Proteínas Recombinantes/inmunología , Células Tumorales CultivadasAsunto(s)
Inmunoglobulina D/sangre , Adulto , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana EdadRESUMEN
The prevalence of serum anti-phospholipid antibodies (aPL) was evaluated in multiple sclerosis (MS) patients to search for a possible association with a distinct form of the disease. Anti-cardiolipin antibodies (Ab) (aCL) and anti-beta 2 glycoprotein I Ab (abeta2GPI) were measured together with antinuclear Ab (ANA), anti-double-stranded DNA Ab (anti-ds DNA) and anti-myelin Ab in 89 patients. Twenty-nine (32.6%) patients had serum aPL, 19xaCL (15 of the IgG and four of the IgM isotype), 14 abeta2GPI (two IgG and 12 IgM) (four of these patients had both Ab). Prevalence of aCL correlated with that of ANA, which were positive in 52 patients (P=0. 005) and with anti-myelin Ab detected in two patients (P=0.046) but not with that of anti-ds DNA (mostly of the IgM class) detected in 28% of case by ELISA. No correlation could be found between aPL and age, sex, duration of the disease from diagnosis, category of MS, clinical course, clinical symptoms, serum IgM levels nor atypical lesions by magnetic resonance imaging. Hence, aCL and abeta2GPI are neither rare in MS nor associated with a specific clinical form of the disease and they cannot be a diagnosis exclusion criteria.
Asunto(s)
Anticuerpos Antifosfolípidos/inmunología , Esclerosis Múltiple/inmunología , Adulto , Anticuerpos Anticardiolipina/sangre , Anticuerpos Anticardiolipina/inmunología , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunología , Anticuerpos Antifosfolípidos/sangre , Femenino , Francia/epidemiología , Glicoproteínas/inmunología , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/fisiopatología , Vaina de Mielina/inmunología , Prevalencia , beta 2 Glicoproteína IRESUMEN
Pathogenic mechanisms of the demyelinating encephalopathy featuring the nervous phase of human African trypanosomiasis (HAT) are largely unknown. They might include autoimmune disorders. A variety of autoantibodies is detected during the disease and we have previously evidenced anti-galactocerebroside (GalC) antibodies in the serum and cerebrospinal fluid (CSF) from patients in the nervous stage (stage II) of HAT. We now show that anti-GalC antibodies recognize an antigen located on the parasite membrane and common to different strains of trypanosomes. By using affinity chromatography with a rabbit anti-GalC antiserum, a 52-kD proteolipid was isolated from the membrane of Trypanosoma brucei (T. b.) brucei AnTat 1.9, AnTat 1. 1E, and T. b. rhodesiense Etat 1.2/R and Etat 1.2/S. Antibodies directed against this antigen were found in the CSF from patients with nervous stage HAT. These CSF also contained anti-GalC antibodies and adsorption with the proteolipid decreased anti-GalC reactivity. Immunization of mice with this antigen induced the production of antibodies which cross-reacted with GalC but no protection from experimental infection with T. b. brucei. These data support the hypothesis that anti-GalC antibodies detected in the CSF from HAT patients might be induced by molecular mimicry with a parasite antigen.
Asunto(s)
Autoanticuerpos/inmunología , Galactosilceramidas/inmunología , Trypanosoma brucei brucei/inmunología , Tripanosomiasis Africana/inmunología , Animales , Especificidad de Anticuerpos , Reacciones Cruzadas , Humanos , Ratones , ConejosRESUMEN
More than 35 years ago, study of an unknown immunoglobulin (Ig) in the serum from a myeloma patient led to the discovery of IgD. Subsequently, the finding that it also exists as a membrane-bound Ig stimulated a large number of studies during the 70s. Then, the interest on IgD shrank, largely because of the lack of known function of secretory IgD (secIgD) and of a stagnating knowledge of the functions of surface IgD. In the recent years, very significant advances followed the tremendous accumulation of data on the physiology of the B cell receptor, of which IgD is the major component, on the role of secIgD in normal and diseased individuals. This review, which is focused on human IgD but integrates data in the mouse and other species when needed, summarizes present data on the structure, synthesis and functions of both membrane and secIgD, IgD receptors and the involvement of IgD in various diseases, especially the hyperIgD syndrome.
Asunto(s)
Inmunoglobulina D/genética , Inmunoglobulina D/fisiología , Animales , Membrana Celular/inmunología , Membrana Celular/metabolismo , Humanos , Inmunoglobulina D/biosíntesis , Inmunoglobulina D/inmunología , Receptores de Superficie Celular/inmunología , Receptores Fc/inmunología , Receptores Inmunológicos/inmunologíaRESUMEN
In stage II human african trypanosomiasis (HAT), which is characterized by central nervous system (CNS) involvement, neurones and oligodendrocytes might be targets of dysimmune processes. Nitric oxide (NO) production by peripheral macrophages is documented in HAT. We studied the production of NO by murine astrocytes and microglia cocultured with Trypanosoma brucei (T. b.) brucei AnTat 1.9. Purified astrocytes or microglia from mouse brains were cocultured with T. b. brucei, and in some instances with interferon (IFN)-gamma, which is known to be released during the disease and also to be a growth factor for trypanosomes. Inducible NO synthase (iNOS) expression was studied by indirect immunofluorescence and reverse transcriptase-polymerase chain reaction. NO production was determined by measuring nitrite generation in culture. Detection of iNOS in astrocytes and microglia in the presence of T. b. brucei, was closely associated with nitrite production and was strongly enhanced by the addition of IFN-gamma to the culture medium. The stimulation of iNOS activity required parasite-cell contact and likely occurred at the transcriptional level. This study demonstrates the induction of iNOS in CNS-related macrophage cells in the presence of trypanosomes and its potentiation by IFN-gamma.
Asunto(s)
Astrocitos/enzimología , Microglía/enzimología , Óxido Nítrico Sintasa/biosíntesis , Trypanosoma brucei brucei/inmunología , Animales , Encéfalo/citología , Comunicación Celular , Separación Celular , Células Cultivadas , Técnicas de Cocultivo , Inducción Enzimática , Interferón gamma/farmacología , Ratones , Óxido Nítrico Sintasa de Tipo IIRESUMEN
IgD is a minor component of serum Ig and the control of IgD secretion is virtually unknown. We measured concentrations of IgD (and IgE and IgM as controls) in culture supernatants of peripheral blood mononuclear cells (PBMC) from 60 normal donors as well as mononuclear cells from 10 tonsils following culture in the absence or presence of CD40 mAb and cytokines. Low levels of IgD were measured in cultures of PBMC, either unstimulated or stimulated by anti-CD40 antibodies. IL-4 and IL-10 significantly increased IgD production by CD40 mAb-stimulated cells in the majority of normal subjects studied, whereas in a limited number of individuals, spontaneous IgD production was either low or high, but with no increase upon stimulation. Spontaneous IgD production by tonsil-derived mononuclear cells was higher than by PBMC and increased after CD40 stimulation and even more in the presence of IL-10, but not IL-4. IL-2 and IFN-gamma exerted a dose-dependent inhibition on spontaneous as well as CD40- and cytokine-induced IgD production by PBMC, but not by tonsil mononuclear cells. Activation by IL-4 of CD40-stimulated purified B cells from tonsil and PBMC, and by IL-10 of tonsil B cells increased IgD production, whereas IL-2 and IFN-gamma had no detectable inhibitory effect. This suggests that accessory cells indirectly regulate IgD synthesis. IgD production induced in PBMC by IL-4 or IL-10 appeared to result from an active synthesis, and correlated with an increase in the number of IgD-containing plasma cells as demonstrated by immunofluorescence and increased expression of secreted IgD transcripts. These findings suggest that IgD production by normal peripheral blood human B cells is regulated positively by T(h)2 cytokines and negatively by T(h)1 cytokines.
Asunto(s)
Linfocitos B/inmunología , Citocinas/fisiología , Inmunoglobulina D/biosíntesis , Células Th2/inmunología , Anticuerpos Monoclonales/inmunología , Antígenos CD40/inmunología , Células Cultivadas , ADN Complementario , Técnica del Anticuerpo Fluorescente , Humanos , Inmunoglobulina E/biosíntesis , Inmunoglobulina M/biosíntesis , Activación de Linfocitos/inmunología , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células TH1/inmunologíaRESUMEN
We have designed an in vivo model in which murine hybridoma cell clones producing human Ig light chains (LC) are administered to mice. Depending on which monoclonal LC is expressed, this model mimics either cast myeloma nephropathy or the pathological condition defined as myeloma-associated Fanconi's syndrome (FS) with LC crystallization. Morphological alterations of the kidney cells are thus obtained in mice. All studied LC are closely related human monoclonal VkappaI proteins, which differ by a limited number of substitutions within the variable region. In the case of an FS monoclonal LC, we show that limited changes introduced through site-directed mutagenesis in the variable domain may suppress formation of intracellular crystals within tubular cells. We also show that multiple peculiarities of the variable region are simultaneously needed to allow LC crystallization; this property thus likely results from a unique LC tridimensional conformation imposed by concomitant somatic mutations of a specific germinally encoded framework.
Asunto(s)
Síndrome de Fanconi/genética , Cadenas Ligeras de Inmunoglobulina/genética , Secuencia de Aminoácidos , Animales , Cristalización , Análisis Mutacional de ADN , Humanos , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Homología de Secuencia de AminoácidoRESUMEN
A 33-year-old man presented an acute motor demyelinating neuropathy following Campylobacter jejuni enteritis. The patient was improved with an IgIV treatment. Clinical features and course time were compatible with the diagnosis of a Guillain-Barré syndrome. The electrophysiologic studies were in favor of multifocal motor neuropathy with conduction blocks. We discuss the nosologic group of this neuropathy.
Asunto(s)
Enfermedades Desmielinizantes/patología , Enfermedad de la Neurona Motora/patología , Polirradiculoneuropatía/patología , Enfermedad Aguda , Adulto , Infecciones por Campylobacter/complicaciones , Infecciones por Campylobacter/terapia , Enfermedades Desmielinizantes/fisiopatología , Electrofisiología , Humanos , Inmunización Pasiva , Masculino , Enfermedad de la Neurona Motora/fisiopatología , Neurología , Polirradiculoneuropatía/fisiopatologíaRESUMEN
The occurrence of abnormally low serum immunoglobulin (Ig) levels is well-known in B chronic lymphocytic leukemia (CLL), but published data on IgG subclass levels are virtually absent. We measured serum IgG subclass levels in 52 B CLL outpatients, most in stage A and untreated, using an indirect immunoenzymatic assay with monoclonal antibodies. Mean levels of all Ig isotypes were lower than in normal controls in the whole group of patients, except for IgG2 in those studied at diagnosis. Levels of IgG1, IgG2, IgA, and IgM were lower in patients with a long disease duration than in those studied earlier. IgG subclass deficiencies occurred in 54% of cases and the most frequently affected isotype was IgG1. Every possible combination of IgG subclass and Ig class deficiencies from the selective deficiency of a single subclass to a combined deficiency of all isotypes was observed. This marked heterogeneity argues against the occurrence of isolated defects of one of the cytokines involved in Ig switching as a cause of hypoimmunoglobulinemia in CLL.
Asunto(s)
Deficiencia de IgG/sangre , Inmunoglobulina G/sangre , Inmunoglobulina G/clasificación , Isotipos de Inmunoglobulinas/sangre , Leucemia Linfocítica Crónica de Células B/inmunología , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Deficiencia de IgG/etiología , Leucemia Linfocítica Crónica de Células B/sangre , Leucemia Linfocítica Crónica de Células B/complicaciones , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To search for a relationship between serum anti-beta2 glycoprotein I (anti-beta2GPI) antibodies and the occurrence of ischaemic complications in giant cell arteritis (GCA), since the latter do not correlate with anti-cardiolipin antibodies (ACL), which are frequently observed in GCA. METHODS: IgG and IgM anti-beta2GPI antibodies and ACL were measured by enzyme-linked immunosorbent assays in sera, collected before treatment, from 45 unselected patients with biopsy-proven GCA, including 15 patients with ischaemic events. RESULTS: IgG and IgM anti-beta2GPI antibodies were not detected in any of the patients, contrasting with the presence of ACL in 51%, of them, without correlation with ischaemia. CONCLUSION: Anti-beta2GPI antibodies are not detectable in GCA, contrasting with the occurrence of ACL, and ischaemic complications are apparently unrelated to the most frequent anti-phospholipid antibodies.
Asunto(s)
Anticoagulantes/inmunología , Autoanticuerpos/análisis , Arteritis de Células Gigantes/inmunología , Glicoproteínas/inmunología , Trombosis/inmunología , Anciano , Anciano de 80 o más Años , Anticuerpos Anticardiolipina/análisis , Biopsia , Cardiolipinas/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Arteritis de Células Gigantes/complicaciones , Humanos , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Masculino , Persona de Mediana Edad , beta 2 Glicoproteína IRESUMEN
We herein report on the first two primary sequences (BOU and RAC) of monoclonal light chains of the lambda type responsible for nonamyloid lambda light chain deposition disease. Both patients were affected with severe forms of myeloma complicated with renal failure. The pathological presentation typically featured Congo red-negative deposits along tubular basement membranes but differed somewhat from the typical "Randall-type" kappa light chain deposition disease: they lacked the prominent glomerulosclerosis pattern often featuring nonamyloid kappa deposits and were associated with cylinders or myeloma casts. Both protein sequences were deduced from those of the corresponding complementary DNAs in the bone marrow plasma cells. For each chain, products of three independent amplifications by polymerase chain reaction were sequenced and found to be identical. BOU and RAC lambda mRNAs had a normal overall structure consisting of Vlambda2 segments rearranged to Jlambda2Clambda2 but displayed a number of unusual features within their primary sequences. These substitutions are likely responsible for changes in light chain conformation that promote their aggregation and deposition along renal tubule basement membranes.
Asunto(s)
Disgammaglobulinemia/genética , Cadenas lambda de Inmunoglobulina/genética , Enfermedades Renales/genética , Mieloma Múltiple/genética , Secuencia de Aminoácidos , Secuencia de Bases , Resultado Fatal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Transcripción GenéticaRESUMEN
Anti-neurofilament (NF) autoantibodies were searched for by enzyme-linked immunosorbent assays (ELISA) in the serum from 85 sporadic amyotrophic lateral sclerosis (ALS) patients, 98 healthy controls and 79 patients with unrelated immunological diseases (Guillain-Barré syndrome, myasthenia gravis and multiple sclerosis). ELISA cutoff value was determined as mean control levels +2 SD and it corresponded to a specificity of 94%. Such high level antibodies were detected in 24.7% of ALS patients contrasting with 12.6% of neurological controls (P<0.05) and only 6.1% of healthy subjects (P<5.10[-4]). In ALS, anti-NF antibodies were significantly associated with a slow evolution, as measured by the mean time spent in the initial functional states. They did not relate with age, sex and clinical form. The predominant isotype of the anti-NF antibodies was IgM lambda by ELISA. In contrast to negative sera, indirect immunohistochemical studies demonstrated that most sera positive for anti-NF antibodies reacted with axons with predominant isotypes restricted to IgM lambda. By using Western blotting, small amounts of serum monoclonal IgM were found with a high frequency in anti-NF antibody-positive patients. These results suggest the possible involvement of anti-NF antibodies in an autoimmune process in a subgroup of ALS patients.
Asunto(s)
Esclerosis Amiotrófica Lateral/inmunología , Autoanticuerpos/sangre , Proteínas de Neurofilamentos/inmunología , Periodicidad , Anciano , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Interleukin 10 (IL-10) has been described as a cytokine inhibitory factor downregulating IL-2 secretion and inducing T cell anergy. The data reported in this study show that preincubation of resting T cells from the human CD4+ clone SP-B21 (and clone TA-23.6) with IL-10 strongly enhances their capacity to further produce IL-2, interferon gamma (IFN-gamma), IL-4 and tumour necrosis factor alpha (TNF-alpha) after subsequent activation. In contrast, when IL-10 was added during the activation step, the previously reported specific inhibition of IL-2 synthesis was observed. Flow cytometric analysis of intracellular IL-2- and IL-4-producing cells revealed that preincubation with IL-10 increased the number of cytokine-producing cells, but did not affect their individual ability to produce these cytokines. We further show that IL-10 plays a dose-dependent role of viability maintenance factor. This effect relates to a direct anti-apoptotic effect of IL-10, which is likely independent of the expression of bcl-2, bcl-x and fas. Such paradoxal properties of IL-10 on T cells should be considered when aiming at using IL-10 as an immunosuppressive molecule in the treatment of diseases.
Asunto(s)
Citocinas/biosíntesis , Interleucina-10/farmacología , Activación de Linfocitos/efectos de los fármacos , Linfocitos T/metabolismo , Células Clonales , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Humanos , Linfocitos T/inmunologíaRESUMEN
The occurrence of kidney diseases was very rarely reported in heavy chain diseases (HCD). At variance with gamma and alpha HCD in which there is no free light chain secretion, about two-thirds of mu HCD patients have urinary Bence Jones (BJ) proteins. We report on a 66 year-old man affected with typical mu HCD who developed renal failure after a 3-year follow-up. He had presented with chronic lymphocytic leukemia with bone marrow vacuolated plasma cells, serum mu HCD protein and serum and urine BJ protein. After an apparent hematological remission following fludarabine therapy, anemia and blood hyperlymphocytosis recurred together with microscopic hematuria, proteinuria and increased creatininemia. Kidney biopsy showed numerous tubular eosinophilic casts which stained for kappa chain determinants by immunofluorescence and an interstitial infiltration by lymphocytes and plasma cells. The hematological and renal condition improved after reinitiation of chemotherapy. This appears to be the first documented report of a light chain-dependent visceral complication in HCD.
Asunto(s)
Enfermedad de las Cadenas Pesadas/complicaciones , Enfermedades Renales/complicaciones , Anciano , Proteína de Bence Jones/metabolismo , Biopsia , Médula Ósea/patología , Estudios de Seguimiento , Enfermedad de las Cadenas Pesadas/inmunología , Enfermedad de las Cadenas Pesadas/metabolismo , Humanos , Inmunoelectroforesis , Cadenas mu de Inmunoglobulina/sangre , Cadenas mu de Inmunoglobulina/orina , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/metabolismo , Leucemia Linfocítica Crónica de Células B/patología , MasculinoRESUMEN
Measurement of serum IgG subclass levels in 3005 patients disclosed abnormally low IgG1 levels with normal levels of the other IgG subclasses and of IgM and IgA in 119 patients, predominantly adults. Not all patients were hypogammaglobulinemic due to nonrare increases of other isotypes, mostly IgM. A familial context of immunodeficiency was frequent, more often combined than selective IgG1 deficiency. A familial association with IgG2 deficiency was found also and IgG1 replaced IgG2 deficiency in 3 cases (and succeeded to or preceded more complex IgG defects in 3 cases, whereas IgG1 deficiency was consistently found at examinations repeated in the absence of therapy in 10 additional cases). Most but not all (83.2%) patients suffered infections, generally moderate, similar to those observed in other selective IgG subclass deficiencies (IgGSD), with predominantly sinorespiratory infections. Other clinical manifestations such as atopy, congenital cardiopathy, and autoimmune diseases were already known in IgGSD but the incidence of asthma was strikingly high (one-fifth of the cases).