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Glicoproteína Asociada a Mielina , Rituximab , Humanos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Glicoproteína Asociada a Mielina/inmunología , Anciano , Adulto , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Alquilantes/uso terapéutico , Alquilantes/efectos adversosAsunto(s)
Abatacept/uso terapéutico , Anemia Hemolítica Autoinmune/tratamiento farmacológico , Antígeno CTLA-4/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Trombocitopenia/tratamiento farmacológico , Adolescente , Adulto , Anemia Hemolítica Autoinmune/genética , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/genética , Niño , Preescolar , Femenino , Humanos , Masculino , Trombocitopenia/genética , Adulto JovenRESUMEN
OBJECTIVES: To demonstrate the bioequivalence between 2 intravenous immunoglobulin (IVIG) preparations, TEGELINE® and ClairYg®, a ready-to-use 5% IVIG, in primary immunodeficiency (PID). Secondary objectives were to assess the efficacy, safety and pharmacokinetics of ClairYg®. METHODS: Twenty-two adult PID patients receiving stable doses of TEGELINE® (5% lyophilized IVIG) were switched to ClairYg® for 6 months. ClairYg® was administered under the same conditions as TEGELINE®, either every 3 or 4 weeks. The primary endpoint was mean average total IgG trough level at steady state with ClairYg® versus TEGELINE®. Clinical efficacy was also assessed in terms of infections and associated events. RESULTS: Bioequivalence was established with a mean average total IgG trough level at steady state being 8.05g/L with TEGELINE® and 9.17g/L with ClairYg® (i.e. geometric mean for the difference between ClairYg® and TEGELINE® was 1.136; [90% CI: 1.092-1.181] P<0.001), within the pre-specified margin to establish bioequivalence (0.80-1.25). Total IgG trough levels remained clinically adequate (>4-6g/L) throughout the study. No patient was hospitalized for infection or had serious bacterial infections while receiving ClairYg®. The median annualized infections rate per patient was similar for both products: 4.35 [0; 21.8] for TEGELINE® and 4.30 [0; 15.1] for ClairYg®. Infections were less common with higher IgG trough levels (>8.16g/L). ClairYg® showed good safety, in particular good hepatic and renal tolerance, and did not induce hemolysis. ClairYg® pharmacokinetics profile was comparable to that of TEGELINE®. CONCLUSION: ClairYg® is safe and effective in the treatment of adult PID.
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Inmunoglobulinas Intravenosas/farmacocinética , Inmunoglobulinas Intravenosas/uso terapéutico , Síndromes de Inmunodeficiencia/terapia , Adulto , Femenino , Francia/epidemiología , Humanos , Inmunoglobulina G/metabolismo , Inmunoglobulina G/uso terapéutico , Síndromes de Inmunodeficiencia/epidemiología , Síndromes de Inmunodeficiencia/metabolismo , Inmunoterapia/métodos , Masculino , Persona de Mediana Edad , Equivalencia Terapéutica , Resultado del Tratamiento , Adulto JovenRESUMEN
Monoclonal IgM anti-myelin-associated glycoprotein (MAG) antibody-related peripheral neuropathy (anti-MAG neuropathy) is predominantly a demyelinating sensory neuropathy with ataxia and distal paresthesia. The clinical course of anti-MAG neuropathy is usually slowly progressive making difficult the identification of clear criteria to start a specific treatment. Although no consensus treatment is yet available, a rituximab-based regimen targeting the B-cell clone producing the monoclonal IgM may be proposed, alone or in combination with alkylating agents or purine analogs. However, in some rare cases, an acute and severe neurological deterioration can occur in few days leading to a rapid loss of autonomy. In these cases, a treatment rapidly removing the monoclonal IgM from the circulation might be useful before initiating a specific therapy. We report successful treatment with plasma exchanges (PE) in four patients presenting with acute neurological deterioration. PE allowed a dramatic and rapid neurological improvement in all patients. PE are safe and may be useful at the initial management of these cases of anti-MAG neuropathy.
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Autoanticuerpos/sangre , Glicoproteína Asociada a Mielina/inmunología , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/terapia , Intercambio Plasmático/métodos , Polineuropatías/complicaciones , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polineuropatías/sangre , Polineuropatías/inmunología , Resultado del TratamientoAsunto(s)
Xantogranuloma Necrobiótico/diagnóstico , Anciano , Anciano de 80 o más Años , Humanos , MasculinoRESUMEN
INTRODUCTION: Common variable immunodeficiency (CVID) is characterized by a defect in antibody production and may be complicated by infectious or non-infectious respiratory disease. BACKGROUND: In addition to recurrent infectious complications, mainly due to encapsulated bacteria, CVID may be complicated by diffuse infiltrative, non-infectious lung disease. The latter may be related to granulomatosis, lymphoid interstitial pneumonia, follicular bronchiolitis, follicular nodular hyperplasia, organizing pneumonia or lymphoma. Different lymphoid histological lesions can co-exist and form a new entity called GLILD (granulomatous lymphocytic interstitial lung disease), which is associated with a poor prognosis. Replacement of immunoglobulins significantly decreases the frequency and severity of infections but has no impact on the non-infectious complications. OUTLOOK: Studies are needed to determine the modalities of follow-up and better understand the long-term progress of GLILD. These studies should improve the management of GLILD in the context of immunosuppressive treatments, which increase the risk of infection in CVID. CONCLUSION: The identification of GLILD, which reflects a variable histological spectrum, rather than a well-defined entity, necessitates revising the approach to diffuse infiltrative lung diseases in CVID.
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Inmunodeficiencia Variable Común/complicaciones , Enfermedades Pulmonares/etiología , Adulto , Humanos , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares Intersticiales/etiologíaRESUMEN
BACKGROUND: Cryofibrinogenaemia is an under-recognized cutaneous thrombotic vasculopathy that may be revealed by purpura or chronic necrotic ulcerations. We report two original cases characterized by their severity, their association with a monoclonal gammopathy and their excellent response to treatment. PATIENTS: A 38-year-old woman was admitted for large necrotic leg ulcers appearing 1 year earlier and already investigated. Non-specific signs were seen on a previous skin biopsy and the diagnosis of a factitious disorder was considered at that time. Further investigations revealed circulating cryofibrinogen associated with IgG kappa monoclonal gammopathy without cryoglobulinaemia. Plasmapheresis followed by bortezomid-dexamethasone to treat the monoclonal gammopathy resulted in rapid and complete healing of the ulcers, militating in favour of its involvement in cryofibrinogen formation. The second patient, a 91-year-old woman, was referred to our department for acute necrotic purpura of the legs. Skin biopsy revealed leukocytoclastic vasculitis. Glomerular nephropathy with acute renal failure and multiple arterial thromboses were associated with the skin condition. The cryofibrinogen assay was positive without cryoglobulinaemia and other causes of vasculitis were ruled out. The main component was monoclonal IgG lambda. Prednisone-cyclophosphamide treatment led to complete healing of the skin lesions and to recovery from the systemic consequences of cryofibrinogen without sequelae. CONCLUSION: Routine screening for cryofibrinogen in plasma should be performed to explore cutaneous symptoms of unexplained thrombotic vasculopathy, even in the presence of a non-specific skin biopsy. Specific treatment of cryofibrinogenaemia associated monoclonal gammopathy appears to be highly effective against manifestations of cryofibrinogenaemia.
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Crioglobulinemia/diagnóstico , Paraproteinemias/diagnóstico , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/patología , Lesión Renal Aguda/terapia , Adulto , Anciano de 80 o más Años , Antiinflamatorios/administración & dosificación , Antineoplásicos/administración & dosificación , Biopsia , Ácidos Borónicos/administración & dosificación , Bortezomib , Crioglobulinemia/patología , Crioglobulinemia/terapia , Crioglobulinas/metabolismo , Ciclofosfamida/administración & dosificación , Dexametasona/administración & dosificación , Quimioterapia Combinada , Femenino , Fibrinógenos Anormales/metabolismo , Humanos , Cadenas kappa de Inmunoglobulina/sangre , Cadenas lambda de Inmunoglobulina/sangre , Riñón/patología , Úlcera de la Pierna/diagnóstico , Úlcera de la Pierna/patología , Úlcera de la Pierna/terapia , Microscopía Fluorescente , Necrosis , Paraproteinemias/patología , Paraproteinemias/terapia , Plasmaféresis , Prednisona/administración & dosificación , Pirazinas/administración & dosificación , Piel/patologíaRESUMEN
Treatment of common variable immunodeficiency disorders (CVID) is based on replacement therapy using intravenous (i.v.) or subcutaneous (s.c.) immunoglobulin (Ig)G. Interindividual variation of IgG dose is common. A total of 380 CVID patients on stable IgG replacement from two prospective cohorts were analysed. An 'efficiency' index was defined as the ratio of serum IgG trough level minus IgG residual to the average weekly dose of IgG infusion. A reduced efficiency of IgG was associated independently with the i.v. route (P < 0·001) and with the presence of at least one CVID disease-related phenotype (lymphoproliferation, autoimmune cytopenia or enteropathy) (P < 0·001). High IgG efficiency was noted in patients homozygotes for the variable number tandem repeat (VNTR) 3/3 polymorphism of the neonatal Fc receptor gene [IgG Fc fragment receptor transporter alpha chain (FCGRT)] promoter, and this was particularly significant in patients treated with IVIG (P < 0.01). In a multivariate analysis, FCGRT VNTR 3/3 genotype (P = 0·008) and high serum albumin (P < 0·001) were associated independently with increased efficiency of i.v. Ig.
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Biomarcadores Farmacológicos , Inmunodeficiencia Variable Común/tratamiento farmacológico , Antígenos de Histocompatibilidad Clase I/genética , Inmunoglobulinas Intravenosas/administración & dosificación , Receptores Fc/genética , Adulto , Estudios de Cohortes , Inmunodeficiencia Variable Común/inmunología , Femenino , Humanos , Inmunoglobulinas Intravenosas/efectos adversos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Repeticiones de Minisatélite/genética , Fenotipo , Polimorfismo Genético , Regiones Promotoras Genéticas/genética , Estudios Prospectivos , Activación Transcripcional/genética , Resultado del TratamientoRESUMEN
Primary immunodeficiency with granulomatosis in the adulthood mainly concern common variable immunodeficiency (CVID). Hypogammaglobulinemia in the adulthood is usually related to a secondary immunodeficiency. When a patient presents with the association of a hypogammaglobulinemia and a granulomatosis, an opportunistic infection must first be ruled out. For unknown reasons, about 10% of the patients affected by CVID also present with granulomatosis. Lesions usually affect the pulmonary tract or the mediastinum. Half of these patients are also affected by an autoimmune cytopenia. Treatment is not codified. Severe pulmonary complications can occur in about 50% of the patients.
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Agammaglobulinemia/etiología , Inmunodeficiencia Variable Común/complicaciones , Granuloma/complicaciones , Adulto , Agammaglobulinemia/tratamiento farmacológico , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/tratamiento farmacológico , Inmunodeficiencia Variable Común/diagnóstico , Inmunodeficiencia Variable Común/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Granuloma/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéuticoRESUMEN
We retrospectively studied a series of 23 patients (median age 50 years, range 29-59 years) with multiple myeloma (MM), treated in first relapse by a sequential autologous-allogeneic tandem approach. Tandem transplantation (TT) consisted in high dose melphalan (HDT) and auto-SCT followed by an (allo-SCT) preceded by two gray TBI non-myeloablative conditioning. All patients received a first HDT as frontline treatment. At day 100 post allo-SCT, complete donor chimerism was detected in 22 patients (95%). Acute GVHD was observed in 19 patients (15 grade I-II (65%) and 4 grade III-IV (17%)). Ten patients (43%) developed an extensive chronic GVHD. The non-relapse mortality at 1 year was 17%. After TT, the overall response rate was 91% (17% partial response, 35% very good partial remission and 39% complete remission). At 2 years, OS was 61%. Median event-free survival and OS were 36.8 and 60 months, respectively. Based on the propensity score matching method, a significant survival advantage could be seen in patients treated with TT as compared with non-allografted patients. Thus, allo-SCT, in TT approach, provides a high response rate with low toxicity and may improve survival of patients with relapsing MM.
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Trasplante de Células Madre Hematopoyéticas/métodos , Mieloma Múltiple/cirugía , Acondicionamiento Pretrasplante , Adulto , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Recurrencia , Estudios Retrospectivos , Quimera por Trasplante , Trasplante Autólogo , Trasplante HomólogoRESUMEN
PURPOSE: Common variable immunodeficiency (CVID), defined by defective production of immunoglobulins, is the most common primary immunodeficiency in adulthood requiring a medical follow-up. Repeated bacterial infections and/or autoimmune manifestations and/or benign lymphoproliferation (including follicular hyperplasia and/or granulomatous disease) are the hallmark of the disease. This review aims at describing recent advances in the understanding and treatment of granulomatous disease in CVID. CURRENT KNOWLEDGE AND KEY POINTS: Clinical features of granulomatous disease in CVID can mimic sarcoidosis, remarkable by the low levels of circulating immunoglobulins. Granulomas may be found in several organs in a single patient, and the main features are pulmonary, lymphoid, cutaneous, hepatic or splenic. The features of CVID is remarkable by the high frequency of autoimmune diseases complicating the immunodeficiency. Some immunological abnormalities have been described in such patients, including lymphopenia, decreased T-cells proliferations to mitogens and antigens. Rare polymorphisms in the gene encoding TNFalpha (Tumor Necrosis Factor) have been identified in CVID patients with granulomatous disease. FUTURE PROSPECTS AND PROJECTS: The evolution of the disease is severe, particularly when the lung is involved. Treatment consists in immunoglobulins substitution, immunosuppressive agents (corticosteroids, cyclophosphamide) and anti-TNFalpha antibodies. These treatments are difficult to manage in such immunocompromised patients.
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Inmunodeficiencia Variable Común/complicaciones , Granuloma/inmunología , Anticuerpos Monoclonales/uso terapéutico , Inmunodeficiencia Variable Común/tratamiento farmacológico , Quimioterapia Combinada , Granuloma/diagnóstico , Granuloma/tratamiento farmacológico , Granuloma/fisiopatología , Humanos , Inmunoglobulinas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Resultado del TratamientoAsunto(s)
Inmunodeficiencia Variable Común/complicaciones , Farmacorresistencia Bacteriana Múltiple , Várices Esofágicas y Gástricas/terapia , Hemorragia Gastrointestinal/terapia , Gastroscopía , Hipertensión Portal/complicaciones , Infecciones por Pseudomonas/etiología , Escleroterapia/efectos adversos , Choque Séptico/etiología , Cianoacrilatos , Resultado Fatal , Femenino , Fluorodesoxiglucosa F18 , Humanos , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Adhesivos Tisulares , Tomografía Computarizada por Rayos XRESUMEN
The t(4;14)(p16;q32) translocation, found in 15% of multiple myeloma (MM) cases, indicates a poor prognosis. Plasma cells (PC) with t(4;14) ectopically express the fibroblast growth factor receptor 3 (FGFR3) tyrosine kinase receptor, which has potential transforming activity and may represent a therapeutic target. To detect FGFR3 protein expression, bone marrow (BM) aspirate from 200 consecutive newly diagnosed (n = 116) or relapsing (n = 74) MM patients was studied by flow cytometry (FC) using anti-CD138 and anti-FGFR3 antibodies. FC data was compared to real time quantitative-polymerase chain reaction (RQ-PCR) of the IGH-MMSET and FGFR3 transcripts. An IGH-MMSET transcript was found in 24/200 patients (12%). In 20 of these, FC detected CD138(+)/FGFR3(+) cells. No expression of FGFR3 was detected in the 4 FGFR3(-) cases by RQ-PCR. FGFR3 was never expressed on PC without t(4;14). Circulating PC (CPC) were detected in patients with (11/11) and patients without (13/41) t(4;14). In 2/8 t(4;14) cases studied longitudinally, coexisting FGFR3(+) and FGFR3(-) CPC were observed. Fluorescent in situ hybridisation (FISH) analysis of the FGFR3(-) subclones showed deletion of the der(14) in one patient. In conclusion, as a supplemental method to RQ-PCR or FISH, FC analysis of FGFR3 expression is a reliable and routinely available method for the detection and management of new therapeutic approaches of t(4;14) MM.
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Biomarcadores de Tumor/metabolismo , Mieloma Múltiple/metabolismo , Células Plasmáticas/metabolismo , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/metabolismo , Biomarcadores de Tumor/sangre , Células de la Médula Ósea/metabolismo , Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 4/genética , Femenino , Citometría de Flujo/métodos , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/genética , Mieloma Múltiple/terapia , Proteínas de Neoplasias/sangre , Proteínas de Neoplasias/metabolismo , Reacción en Cadena de la Polimerasa/métodos , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/sangre , Translocación Genética , Células Tumorales CultivadasRESUMEN
Hematopoietic stem cell (HSC) transplantation, whatever its conditions, is associated with an increased risk of infections and tumoral complications, because of a delayed immune reconstitution. T-cell regeneration has been mostly investigated and appears to come more from graft and/or host mature T-cells, rather than from the differentiation/maturation of reinfused progenitors. In allogeneic setting, the immune defect is enhanced by the immune host/donor conflict and the use of prophylactic or curative immunosuppressive therapy. The tools used for studying post-transplant immunity are the following: immunophenotyping (kinetics and alterations of lymphocyte subset reconstitution), functional studies of T cell proliferation, cytokine production, cytotoxicity and signal transduction, as well as studies of T cell repertoire diversity. The CD4/CD8 cell immunophenotyping might be enough for routine clinical evaluation, allowing an adapted prophylaxis of opportunistic infections in those immune-suppressed patients, while functional assays might be useful to evaluate the persistence overtime of defects in immune reconstitution. These overall assays are useful both for basic and clinical research and allow better understanding in the mechanisms for T cell regeneration in the diverse types of HSC transplants performed nowadays particularly after graft of purified HSC where immune reconstitution remains a key question.