RESUMEN
INTRODUCTION: Immune monitoring of monoclonal antibodies is a helpful tool in optimizing the management of patients treated with TNF blockers, especially in gastroenterology. In contrast, studies evaluating the interest of such monitoring are lacking for other monoclonal antibodies used in autoimmune diseases, including rituximab despite its widespread use in the field for almost 15 years. Hence, we conducted a study whose goal was to describe the clinical and biological characteristics of all patients who had a rituximab immune monitoring. METHODS: All the clinical, biological and therapeutic data attached to the demands (from 2015 onwards) we received for immune monitoring of rituximab (measurements of rituximab serum levels and anti-rituximab antibodies using the drug-sensitive assay LISA-TRACKER Duo Rituximab®), were retrospectively reviewed. Suspected cases of hypersensitivity and secondary non-response were included. RESULTS: Several medical specialities (nephrology, haematology, neurology, rheumatology, internal medicine) were represented among the 18 records included in the study (out of 23 demands), 10 being suspected cases of hypersensitivity and 8 secondary non-responders. All 6 patients whose symptoms were consistent with the classical presentation of serum sickness, as well as half of the secondary non-responders, were positive for antirituximab antibodies. CONCLUSION: This detailed real world case study illustrates the potential benefits of rituximab immune monitoring (especially anti-rituximab antibodies) in autoimmune diseases, suggesting it could be helpful in suspected cases of serum sickness, as well as secondary non-response (B-cell non-depletion being an early red flag). Larger and disease-specific studies are warranted to support these findings.
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Enfermedades Autoinmunes , Factores Inmunológicos , Anticuerpos Monoclonales , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/epidemiología , Humanos , Estudios Retrospectivos , Rituximab/uso terapéuticoRESUMEN
Occurrence of cancer after renal transplantation remains a major problem, and the second cause of death. We performed a retrospective analysis of first cancer, first skin cancer, and first organ cancer (including posttransplant lymphoproliferative disease [PTLD]) among 1265 cases from 1979 to 2006. The occurrence of cancer was clearly a time-dependent event justifiying the use of Kaplan-Meier survival and Cox regression methods. The 10-year cumulative incidences of first cancer, first skin cancer, and first organ cancer were 24.6%, 14.5%, and 14.5%, respectively. Recipient age was a major, independent risk factor for the 3 endpoints with a 6% increased relative risk for each year increment (P < .0001). Female gender was also a major, independent risk factor, but only for skin cancer (P = .0002). We could not demonstrate any difference between the immunosuppressive drugs used for induction or maintenance therapy, especially between antithymocyte globulin (ATG) vs anti-CD25, cyclosporine vs tacrolimus, and azathioprine vs mycophenolate mofetil. Large cohorts are needed with strict stratifications for recipient age and gender to detect any difference, if any, among the drugs.
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Trasplante de Riñón/efectos adversos , Neoplasias/epidemiología , Cadáver , Estudios de Cohortes , Femenino , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Trasplante de Riñón/inmunología , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , Prednisolona/uso terapéutico , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Cutáneas/epidemiología , Donantes de TejidosRESUMEN
Idiopathic membranous nephropathy (IMN) has a strong association with the major histocompatibility complex HLA B8DR3(17)DQ2 haplotype. The tumor necrosis factor (TNF)A gene is located within the major histocompatibility complex region on chromosome 6. We have studied the influence of two functional polymorphisms; the -308 (promoter region) and the TNFd microsatellites on initiation and/or progression of IMN. This was a case-control study comparing data from 100 Caucasians patients (67 male subjects; 67%) with IMN to 232 Caucasians local controls (171 male subjects; 74%). We have analyzed genotypes and alleles distributions and the role of these polymorphisms in disease progression towards end-stage renal failure or patient death. For -308 TNFA polymorphism, distribution of genotypes was significantly different between IMN and controls (chi(2)=16.25; P=0.0003): the A2 allele frequency was 28.0% in IMN vs 15.3% in controls (chi(2)=14.57; P=0.0001). For TNFd polymorphism, alleles distribution (from d1 to d7) was also significantly different between IMN and controls (chi(2)=56.74; P<0.0001) with both diminished d3 allele frequency (chi(2)=27.30; P<0.0001; Pc=0.001) and increased d2 allele frequency (chi(2)=29.95; P<0.0001; Pc=0.001) in IMN. We could not isolate any significant and independent influence of these different genotypes on IMN disease progression. The TNFA2 and TNFd2 alleles were strongly associated with occurrence/initiation of IMN and should be considered as susceptibility genes for this disease.
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Predisposición Genética a la Enfermedad , Glomerulonefritis Membranosa/genética , Polimorfismo Genético , Factor de Necrosis Tumoral alfa/genética , Adulto , Alelos , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Frecuencia de los Genes , Humanos , Masculino , Repeticiones de Microsatélite/genética , Persona de Mediana Edad , Regiones Promotoras Genéticas/genéticaAsunto(s)
Acidosis Tubular Renal/etiología , Síndrome de Sjögren/complicaciones , Acidosis Tubular Renal/patología , Adulto , Biopsia , Femenino , Humanos , Hipopotasemia/etiología , Riñón/patología , Nefritis Intersticial/patología , Nefrocalcinosis/diagnóstico por imagen , Nefrocalcinosis/etiología , Síndrome de Sjögren/diagnóstico , Factores de Tiempo , UrografíaRESUMEN
BACKGROUND: Arterial hypertension (HT), secondary to cyclosporine A (CsA) used as main immunosuppressive treatment in renal transplantation (RTx), is very frequent (70%), usually severe and explained mostly by vasoconstriction of the glomerular afferent arteriole with secondary sodium and water retention. MATERIAL AND METHODS: In a retrospective study, we have analyzed 294 consecutive recipients receiving a first renal cadaveric allograft and all treated with CsA (the majority with triple therapy). We studied, by molecular biology, the polymorphism of genes previously implicated in essential HT such as: angiotensin-converting enzyme (ACE: II, ID and DD), angiotensinogen (AGT: MM, MT and TT), angiotensin II type 1 receptor (AT1-R: AA, AC and CC) and endothelial constitutive nitric oxide synthase (ecNOS: aa, ab and bb), and correlated the data to the prevalence and severity of post-Tx HT. This cohort included 195 (66%) males and 99 females with a mean age of 42 years at time of Tx. The presence and severity of post-Tx HT were indicated by initial persistent blood pressure over 140/90 mmHg with the need for at least one anti-hypertensive drug and by the number of anti-HT medications required to achieve its control. RESULTS: The distribution of the specific alleles and genotypes for ACE, AGT, AT1-R, and ecNOS was not different in transplant recipients compared to 181 controls. At 5 years post-Tx, the prevalence of HT was 72% (169 out of 235) among functioning grafts. There was no significant difference for ACE, AGT, AT1R and ecNOS genotypes distribution between hypertensive vs non-HT recipients. The number of anti-hypertensive drugs prescribed was not different among ACE, AGT, and AT1-R genotypes. However, the a allele and the non-bb genotype (aa + ab) for ecNOS were significantly (p = 0.001) associated with a less severe HT, needing fewer anti-HT drugs. At 10 years post-Tx, the HT prevalence remained high 78% (67 out of 86) among functioning Tx. However, the limited numbers did not allow further correlation. CONCLUSIONS: This study produced mainly negative results except for ecNOS-a allele, which seems to protect against severe hypertension. The explanation remains speculative but probably relates to the known cyclosporine-induced upregulation of ecNOS gene and enzyme activity.
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Angiotensinógeno/genética , Ciclosporina/efectos adversos , Hipertensión/genética , Inmunosupresores/efectos adversos , Trasplante de Riñón , Óxido Nítrico Sintasa/genética , Peptidil-Dipeptidasa A/genética , Receptores de Angiotensina/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Genotipo , Supervivencia de Injerto , Humanos , Hipertensión/inducido químicamente , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Receptor de Angiotensina Tipo 1 , Estudios RetrospectivosAsunto(s)
Anticuerpos Monoclonales/uso terapéutico , Suero Antilinfocítico/uso terapéutico , Trasplante de Riñón/inmunología , Proteínas Recombinantes de Fusión , Enfermedad Aguda , Basiliximab , Infecciones por Citomegalovirus/epidemiología , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , Prueba de Histocompatibilidad , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Trasplante de Riñón/métodos , Proyectos Piloto , Complicaciones Posoperatorias/clasificación , Complicaciones Posoperatorias/epidemiologíaRESUMEN
BACKGROUND: Sensitized kidney allograft recipients require special management to improve their outcome. One strategy is heavy immunosuppression with antilymphocyte antibodies. Controversy continues about the actual advantage of induction protocols whilst infections and cancers are a constant risk. In addition, little is known about how to handle sensitized patients with low levels of sensitization. METHODS: In this study, we randomized sensitized renal transplant recipients, who received prophylactic treatment with or without antithymocyte globulin (ATG), in addition to a standard triple regimen consisting of cyclosporin, steroids and azathioprine at ATG discontinuation. The induction treatment consisted of a low-dose ATG course over 10 days. Randomization was stratified on the maximum PRA, according to the five following classes: 5% < PRA < or = 20%, 20% < PRA < or = 40%, 40% < PRA < or = 60%, 60% < PRA < or = 80% and 80% < PRA < or = 100%. RESULTS: Eighty nine patients were enrolled: 47 patients received ATG and 42 did not. ATG induction lowered the incidence of biopsy-proven acute rejection episodes from 64 to 38%, increased 1 year graft survival from 76 to 89% and was associated with a higher 1 year inulin clearance (37+/-15 vs 49+/-18 ml/min). ATG-associated side effects were restricted to leucopenia and thrombocytopenia, whereas bacterial and viral infections, gammopathies and cancers did not occur more frequently. ATG induction benefited all sensitized patients, and not only the hypersensitized patients. CONCLUSIONS: We conclude that ATG induction is beneficial for all sensitized patients, regardless of their level of sensitization, with regard to acute rejection episodes, graft survival and graft function. Low-dose ATG is sufficient and prevents additional complications.