ABSTRACT
OBJECTIVE: The renin-angiotensin-aldosterone system (RAAS) and glucocorticoids (GCs) are involved in vascular remodeling and fibrosis, but have not been extensively studied in systemic sclerosis (SSc). Our aim was to investigate the RAAS and GC hormones in SSc patients. METHODS: Serum levels of renin (dosage and activity), aldosterone and its precursors (DOC, B, 18-OH-DOC, 18-OH-B), and GCs (cortisol, cortisone, 11-deoxycortisol, 18-OH-F) were assessed in 122 SSc patients and 52 healthy controls. After applying stringent inclusion criteria aimed at ensuring accurate hormone assessments (exclusion of interfering drugs, strict sampling conditions), we analyzed RAAS hormones in 61 patients, and GCs in 96 patients. Hormone levels were compared between patients and controls; and associations with disease characteristics were assessed in patients. RESULTS: Regarding RAAS hormones, SSc patients displayed significantly lower aldosterone levels (although within normal range), similar renin levels, and higher B levels than controls. Abnormal RAAS hormone levels were associated with a more severe SSc phenotype (lung and skin fibrosis, heart and pulmonary vascular involvements, inflammation). Regarding GC hormones, SSc patients had higher levels of cortisol, 11-desoxycortisol (precursor) and 18-OH-F (metabolite) but lower levels of cortisone (inactive counterpart) than controls.RAAS hormone levels were assessed in 5 SSc patients before and during scleroderma renal crisis (SRC): concentrations varied considerably between patients, but consistently included normal/increased aldosterone levels and elevated renin levels. CONCLUSION: RAAS and GC hormones are abnormally produced in SSc patients, especially in patients with severe SSc and during SRC. This could suggest a participation of these hormonal systems in SSc pathogenesis.
ABSTRACT
INTRODUCTION: Immunological checkpoint inhibitors (ICI) have led to a therapeutic revolution in the management of many cancers and indications are increasing. Neurological complications seem to have a profile quite distinct from that of toxicities related to chemotherapy, although it is possible that some manifestations remain under-reported or misdiagnosed. OBJECTIVES: (i) To evaluate the value of a self-questionnaire in screening for neurological ICI-related complications. (ii) To investigate whether, apart from the subacute complications described in the literature, neurological complications of more insidious onset might occur. METHOD: Patients followed in dermatology department for skin cancers treated with ICI, completed every infusion a neurological screening auto-questionnaire. Patients were selected for a neurological expertise based on the questionnaire's data. RESULTS: In total, 149 patients completed≥1 questionnaire, with a median delay of 174 days from the start of treatment. A total of 229 questionnaires were completed between July 2019 and December 2019. 38 patients were identified for a neurological consultation. None of these patients had a neurological event attributable to ICI. During the follow-up, only one patient had a neurological event related to ICI, which was not revealed by the questionnaire. DISCUSSION: Neurological signs in ICI-treated-skin-cancer context are more often due to tumoral progression. Neurological complications of ICI remain rare and unpredictable. The systematic neurological questionnaire has not been shown to be useful in this context. These results highlight the need to educate patients about possible subacute signs that should lead to contact the treating physicians and the need for a close cooperation between dermatologists/oncologists and neurologists.
Subject(s)
Antineoplastic Agents, Immunological , Neoplasms , Humans , Antineoplastic Agents, Immunological/adverse effects , Neoplasms/complications , Neoplasms/drug therapy , Surveys and Questionnaires , Retrospective StudiesABSTRACT
Background/Purpose Long-term anticoagulation is the standard treatment for thrombotic antiphospholipid syndrome (APS). However, in daily practice, the question of withdrawing anticoagulation may arise, without any evidence-based recommendations. This study aimed to assess outcomes in APS patients after anticoagulation withdrawal. Methods Thrombotic APS patients followed in our centre, whose anticoagulation was withdrawn after APS diagnosis, were retrospectively selected, and were match-controlled with patients under anticoagulation, based on sex, age, APS clinical phenotype and disease duration. Results Thirty cases with anticoagulation withdrawal were included. Median follow-up was 51 months (12-124). The risk of thrombotic relapse was higher in cases compared to controls (7.3% versus 1.5% patient-year ( p = 0.01); hazard ratio 4.8; 95% confidence interval (1.4-16.7)). Male gender, anti-ß2GP1 and triple positivity at inclusion were predictive factors for thrombotic relapse. Conversely, aspirin prescription was a protective factor against relapses. Persistence of LA, anti-ß2GP1 and triple positivity over time were associated with a higher risk of thrombosis and aPL disappearance with a lower risk. Conclusion In our study, anticoagulation withdrawal was associated with an increased risk of thrombotic relapse. Our findings emphasize the influence of anti-ß2GP1 and triple positivity persistence over time on the risk of relapse and the benefit of aspirin prescription when anticoagulation has been withdrawn.
Subject(s)
Anticoagulants/administration & dosage , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/drug therapy , Thrombosis/complications , Thrombosis/drug therapy , Adult , Antibodies, Antiphospholipid/immunology , Anticoagulants/therapeutic use , Aspirin/therapeutic use , Blood Coagulation/drug effects , Case-Control Studies , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Recurrence , Retrospective Studies , Risk Factors , Young AdultABSTRACT
Systemic sclerosis (SSc) is an orphan disease characterized by progressive fibrosis of the skin and internal organs. Aside from vasculopathy and fibrotic processes, its pathogenesis involves an aberrant activation of immune cells, among which B cells seem to play a significant role. Indeed, B cell homeostasis is disturbed during SSc: the memory subset is activated and displays an increased susceptibility to apoptosis, which is responsible for their decreased number. This chronic loss of B cells enhances bone marrow production of the naïve subset that accounts for their increased number in peripheral blood. This permanent activation state can be explained mainly by two mechanisms: a dysregulation of B cell receptor (BCR) signaling, and an overproduction of B cell survival signals, B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). These disturbances of B cell homeostasis induce several functional anomalies that participate in the inflammatory and fibrotic events observed during SSc: autoantibody production (some being directly pathogenic); secretion of pro-inflammatory and pro-fibrotic cytokines (interleukin-6); direct cooperation with other SSc-involved cells [fibroblasts, through transforming growth factor-ß (TGF-ß) signaling, and T cells]. These data justify the evaluation of anti-B cell strategies as therapeutic options for SSc, such as B cell depletion or blockage of B cell survival signaling.
Subject(s)
B-Lymphocytes/physiology , Scleroderma, Systemic/immunology , Animals , Autoantibodies/physiology , Cell Communication/immunology , Humans , Immunotherapy/methods , Molecular Targeted Therapy , Scleroderma, Systemic/pathology , Scleroderma, Systemic/therapy , T-Lymphocytes/immunologyABSTRACT
Introduction The long-term risk of first thrombosis and benefit of prophylaxis in antiphospholipid antibody (aPL) carriers without history of thrombosis or obstetrical morbidity is poorly known. This study aimed to evaluate the long-term rate and risk factors associated with a first thrombosis in those patients. Patients and methods After a prior study ended in December 2005 and was already published, we extended the follow-up period of our cohort of aPL carriers. Results Ninety-eight of the 103 patients of the previous study were included. The annual first thrombosis rate was 2.3% per patient-year during a median of 13 years (6-17). None of the baseline characteristics was predictive of risk of first thrombosis, but persistent aPL over time were associated with an increased risk. The stronger association was found in triple aPL-positive carriers: OR 3.38 (95% CI: 1.24-9.22). Of note, conversely to our previous findings, no benefit of aspirin prophylaxis was observed. Conclusion The risk of first thrombosis in aPL carriers without history of thrombosis or obstetrical morbidity was significant, persisted linearly over time and was associated with persistent aPL. This risk was especially increased in triple aPL-positive carriers, in whom a close follow-up seems to be necessary. Nevertheless, the benefit of aspirin prophylaxis remained unclear.
Subject(s)
Antibodies, Antiphospholipid/blood , Antiphospholipid Syndrome/blood , Thrombosis/etiology , Adult , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/drug therapy , Aspirin/administration & dosage , Biomarkers/blood , Chi-Square Distribution , Disease-Free Survival , Female , Fibrinolytic Agents/administration & dosage , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Linear Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Proportional Hazards Models , Retrospective Studies , Risk Factors , Thrombosis/blood , Thrombosis/diagnosis , Thrombosis/prevention & control , Time Factors , Treatment OutcomeABSTRACT
AIM: Morbid obesity increases the risk of cardiovascular disease (CVD). The receptor for advanced glycation end-products (RAGE) is implicated in proinflammatory processes that underlie CVD. Its soluble form (sRAGE) has been proposed as a vascular biomarker. Recently, anti-sRAGE autoantibodies were described and found to be increased in diseases where RAGE is overexpressed. This study aimed to investigate serum levels of anti-sRAGE autoantibodies in morbidly obese patients. METHODS: After exclusion based on specific criteria, 150 subjects (50 normoglycemics, 50 glucose-intolerants and 50 diabetics) were randomly recruited from a cohort of 750 obese patients (ABOS). Serum sRAGE and anti-sRAGE autoantibodies were measured before bariatric surgery. Sixty-nine patients were followed for up to 1year after gastric bypass, and their levels of sRAGE and anti-sRAGE autoantibodies measured. The control group consisted of healthy blood donors. RESULTS: Compared with controls, baseline levels of sRAGE and anti-sRAGE autoantibodies were significantly higher in all obese patients independently of glucose regulation (P<0.001). At 1year after gastric bypass, sRAGE and anti-sRAGE were decreased (P<0.001). The decrease in anti-sRAGE autoantibodies was correlated with an increase in high-density lipoprotein (HDL; P=0.02). CONCLUSION: Independently of previous diabetic status, morbid obesity increases sRAGE and anti-sRAGE levels. Weight loss after gastric bypass is followed by a decrease in both titres. The decrease in anti-sRAGE correlates with an increase in HDL.
Subject(s)
Autoantibodies/blood , Cardiovascular Diseases/immunology , Diabetic Angiopathies/immunology , Gastric Bypass , Insulin Resistance/immunology , Lipoproteins, HDL/metabolism , Obesity, Morbid/immunology , Receptors, Immunologic/immunology , Adult , Biomarkers/blood , Blood Glucose/metabolism , Cardiovascular Diseases/prevention & control , Diabetic Angiopathies/prevention & control , Down-Regulation , Female , Follow-Up Studies , Humans , Inflammation/immunology , Male , Obesity, Morbid/surgery , Receptor for Advanced Glycation End Products , Receptors, Immunologic/blood , Weight Loss/immunologyABSTRACT
BACKGROUND: Melanoma is an immunogenic tumour type frequently associated with spontaneous auto-immune manifestations such as spontaneous regression, vitiligo-like reactions or auto-immune retinopathy, which seem to be associated with better prognosis. OBJECTIVES: The aim of this prospective study was to evaluate the correlation between spontaneous autoimmunity and survival in patients with stage IV melanoma. METHODS: From 2007 to 2008, 103 patients were studied with antithyroid and antinuclear auto antibody assays performed every 6 months. Any detectable occurrence of a spontaneous self antibody (SpSA) at the upper detection limit, at least for one assay, was considered to be a biological marker of autoimmunity. RESULTS: Univariate and multivariate analyses confirmed significantly longer survival in the absence of known primary melanoma (P = 0.044) and in the presence of marker of biologic autoimmunity, independently of previous immunotherapy (P = 0.045). CONCLUSIONS: This prospective and comparative study is, to our knowledge, the first to report the frequency of SpSA in stage IV melanoma. Our results suggest that spontaneous autoimmunity, through a rupture of self-tolerance, is a good prognostic factor in a subgroup of patients with stage IV melanoma.
Subject(s)
Autoantibodies/immunology , Melanoma/immunology , Melanoma/mortality , Skin Neoplasms/immunology , Skin Neoplasms/mortality , Adult , Aged , Analysis of Variance , Autoimmunity/physiology , Biomarkers/analysis , Cohort Studies , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Melanoma/secondary , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness/pathology , Neoplasm Metastasis , Neoplasm Staging , Prognosis , Prospective Studies , Skin Neoplasms/pathology , Survival AnalysisABSTRACT
The impact of autoimmunity on malaria-infection evolution reported by various works has led us to compare reactive patterns of self-dependent systemic IgG from 54 patients aged less than 15 years old to those from 46 subjects older than 15 years. These subjects were divided into 34 Plasmodium falciparum asymptomatic carriers (ACs), 30 cases of uncomplicated malaria (UM), and 36 patients suffering from cerebral malaria (CM) living in the same endemic area. The reactivity of the plasma antibodies against human brain tissue extract was assessed by western blotting. Comparative analysis of reactive bands (linear discriminant analysis, LDA) revealed the existence of patterns that distinguish, among the more susceptible subjects aged less than 15 years old, the different clinical forms. In contrast, in less susceptible subjects aged more than 15 years old, the patterns are homogenous and do not allow the separation of these clinical forms. This self-reactive repertoire might be witnessed as an imprint of the clinical tolerance acquired during the years of living in endemic areas. The singularity of this profile under the age of 15 years might have a prognostic value.
Subject(s)
Aging/immunology , Autoantibodies/immunology , Immunoglobulin G/immunology , Malaria, Cerebral/immunology , Malaria, Falciparum/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibody Specificity , Autoantibodies/blood , Autoantigens/immunology , Brain/immunology , Carrier State/epidemiology , Carrier State/immunology , Child , Child, Preschool , Cote d'Ivoire/epidemiology , Disease Progression , Disease Susceptibility , Endemic Diseases , Environmental Exposure , Female , Humans , Immune Tolerance , Immunoglobulin G/blood , Infant , Malaria, Cerebral/epidemiology , Malaria, Cerebral/etiology , Malaria, Falciparum/epidemiology , Male , Middle Aged , Nerve Tissue Proteins/immunology , Prognosis , Young AdultABSTRACT
Systemic lupus erythematosus (SLE) is an autoimmune disease, which primarily affects skin and joints. Peripheral neurologic syndrome and central nervous system (CNS) manifestations are common in lupus patients but are not always attributable to lupus itself. A classification, published in 1999 by the American College of Rheumatology (ACR) research committee, described 12 CNS syndromes and seven peripheral neurologic syndromes compatible with "neuropsychiatric systemic lupus erythematosus" (NPSLE). Despite this consensus, studies which have been published since 1999 have reported a prevalence of NPSLE varying from 20 to 97 %, which shows the diagnosis difficulty and the heterogeneity of neuropsychiatric manifestations in SLE. In order to understand the limits of this classification, we propose in this first part an exhaustive review of publications describing neuropsychiatric manifestations according to the ACR 1999 classification. We also detail case definitions, prevalence and risk factors, clinical characteristics and diagnosis of each lupus-related psychiatric and CNS manifestation.
Subject(s)
Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/therapy , Lupus Vasculitis, Central Nervous System/diagnosis , Lupus Vasculitis, Central Nervous System/therapy , Anxiety Disorders/diagnosis , Anxiety Disorders/epidemiology , Anxiety Disorders/etiology , Cognition Disorders/diagnosis , Cognition Disorders/epidemiology , Cognition Disorders/etiology , Diagnosis, Differential , Epilepsy/diagnosis , Epilepsy/epidemiology , Epilepsy/etiology , Humans , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/epidemiology , Lupus Vasculitis, Central Nervous System/epidemiology , Lupus Vasculitis, Central Nervous System/etiology , Neuropsychological Tests , PrevalenceABSTRACT
Neurological and psychiatric manifestations of systemic lupus erythematosus are a heterogeneous set of clinical manifestations grouped under the term of "neuropsychiatric systemic lupus erythematosus". The classification of these manifestations published in 1999 has harmonized the definitions cases used in the studies but did not help the clinician to positively identify a specific manifestation of lupus or a neurological or psychiatric event occurred independently of the disease. Published cases series help us to identify neurological or psychiatric manifestations of lupus but modern diagnosis tools contribution have to be evaluated in order to optimize diagnosis management of such manifestations and to distinguish specific events related to lupus and independent manifestations. In this second part of our literature review about neuropsychiatric lupus, we propose to identify arguments, which could be in favor of lupus responsibility in front of a neurological or psychiatric event, and immunosuppressive treatments which are recommended.
Subject(s)
Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/therapy , Lupus Vasculitis, Central Nervous System/diagnosis , Lupus Vasculitis, Central Nervous System/therapy , Neuropsychological Tests , Algorithms , Central Nervous System/physiopathology , Diagnostic Techniques, Neurological , Humans , Incidence , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/epidemiology , Lupus Vasculitis, Central Nervous System/epidemiology , Lupus Vasculitis, Central Nervous System/etiologyABSTRACT
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by arterial and/or venous thromboses and/or pregnancy-associated morbidity. Some patients develop only obstetric complications (obstetric APS), but data on the frequency of thrombotic events during the follow-up of these patients are scarce. This study was undertaken to evaluate the rate of thrombotic events after obstetric APS diagnosis according to the 2006 revised criteria. In total, 32 obstetric APS patients were retrospectively studied, with mean follow-up of 50 ± 37 months. After delivery, aspirin was prescribed to all patients as primary thrombosis prevention. The thrombosis rate was 3.3/100 patient-years and was 4.6, 4.5 and 10/100 patient-years when we considered at least two antiphospholipid antibody positivities (among lupus anticoagulant, anticardiolipin and anti-ß2-glycoprotein-I), antinuclear antibody positivity or systemic lupus erythematosus-associated APS patients, respectively. The thrombosis rate was high after obstetric APS diagnosis, even for patients taking aspirin. Larger, prospective studies are needed to confirm this high frequency and determine the associated risk factors.
Subject(s)
Antiphospholipid Syndrome/complications , Pregnancy Complications/immunology , Thrombosis/etiology , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Antibodies, Antiphospholipid/blood , Antibodies, Antiphospholipid/immunology , Antiphospholipid Syndrome/immunology , Antiphospholipid Syndrome/physiopathology , Aspirin/therapeutic use , Female , Fibrinolytic Agents/therapeutic use , Follow-Up Studies , Humans , Pregnancy , Retrospective Studies , Risk Factors , Thrombosis/immunology , Thrombosis/prevention & control , Young AdultSubject(s)
Inflammation/immunology , Threonine-tRNA Ligase/immunology , Adult , Aged , Antibodies , Cell Line , Echocardiography/methods , Female , Humans , Male , Middle Aged , Myositis/blood , Myositis/immunology , Phenotype , Prevalence , Prognosis , Retrospective StudiesABSTRACT
BACKGROUND: Autoimmune polyendocrine syndrome type 1 (APS1) has been poorly evaluated in France. We focused on the north-western part of the country to describe clinical phenotypes, especially severe forms of the disease, and AIRE gene mutations. METHODS: Clinical and immunological data were collected, and pathological mutations were identified by DNA sequencing. RESULTS: Nineteen patients were identified with APS1. Clinical manifestations varied greatly, showing 1-10 components. Mucocutaneous candidiasis, adrenal failure, hypoparathyroidism, alopecia and other severe infections were the most frequent components. Four patients had severe forms, needing immunosuppressive therapy: 2 for hepatitis; 1 for severe malabsorption, and 1 for a T cell large granular lymphocytic leukemia. These therapies were very effective but caused general discomfort. One patient died of septicemia. Four different AIRE gene mutations were identified, and a 13-bp deletion in exon 8 (c.967-979del13) was the most prevalent. There was at least one allele correlating with this mutation and alopecia occurrence (p = 0.003). No novel mutation was detected. CONCLUSION: APS1 appears to be rare in north-western France. We identified 4 cases with a severe form needing immunosuppressive therapy. The AIRE gene mutations are more like those found in north-western Europe than those found in Finland.
Subject(s)
Immunosuppression Therapy , Polymorphism, Genetic , Transcription Factors/genetics , Adolescent , Adult , Alopecia/epidemiology , Alopecia/genetics , Child , DNA Mutational Analysis , Female , France/epidemiology , Genotype , Humans , Immunosuppressive Agents , Male , Middle Aged , Mutation , Phenotype , Polyendocrinopathies, Autoimmune/epidemiology , Polyendocrinopathies, Autoimmune/genetics , Polyendocrinopathies, Autoimmune/physiopathology , Polyendocrinopathies, Autoimmune/therapy , Severity of Illness Index , Young Adult , AIRE ProteinABSTRACT
OBJECTIVE: We previously showed that serum IgG repertoires distinguished multiple sclerosis (MS) patients from healthy subjects and from patients with other inflammatory neurological diseases (OIND). We questioned whether the serum IgG repertoire of patients presenting a clinically isolated syndrome (CIS) could predict MS. METHODS: The global IgG immune responses against brain antigens in sera from 50 CIS patients were evaluated by immunoblotting. The IgG reactivities were compared with those from MS sera (n = 82), healthy sera (n = 27), and sera from OIND (n = 42). A linear discriminant analysis (LDA) defined a score for each individual. RESULTS: About 78% of scores obtained from CIS patients were located in the "MS area." During the follow-up (3.5 +/- 1.3 years), 28 patients fulfilled the McDonald criteria for MS, 15 patients remained CIS, and 7 patients developed OIND. Among the patients with an LDA score in the "MS area," 61.5% converted to MS. DISCUSSION: Our results suggest that a pathological distortion of the self-reactive IgG repertoire occurs early so that immunomodulating treatment should be started as early as possible; they also highlight the early involvement of B cells in the physiopathological process in MS.
Subject(s)
B-Lymphocytes/immunology , Biomarkers/blood , Immunoglobulin G/blood , Multiple Sclerosis/epidemiology , Multiple Sclerosis/immunology , Antibody Specificity , Brain/immunology , Female , Humans , Male , Nerve Tissue Proteins/immunology , Predictive Value of Tests , Risk Factors , Seroepidemiologic StudiesABSTRACT
One hundred and three consecutive asymptomatic anti-phospholipid (aPL) antibody-positive carriers, taking aspirin (n=75) or not (n=28), were studied retrospectively to determine whether aspirin could provide primary prevention of anti-phospholipid syndrome (APS) symptoms. All patients positive for anti-cardiolipin antibodies (aCL; >25 UGPL or UMPL) and/or lupus anti-coagulant were followed for a mean of 64+/-24.7 months.Among aPL-positive patients, 37 had systemic lupus erythematosus (SLE), 20 had prolonged activated partial thromboplastin times, 19 had other connective tissue diseases, 16 had autoimmune thrombocytopenia (AIT), 11 had diverse diseases. Nineteen patients experienced thrombotic event(s) during follow-up. Clinical features, biological parameters and hydroxychloroquine use were comparable for the two groups, but thrombotic events differed (log-rank test; P=0.02). Four of the 10 SLE patients not taking aspirin developed thrombosis compared with 3/27 SLE patients taking aspirin (log-rank test; P=0.03). Anti-phospholipid -positive patients with AIT developed fewer thromboses while taking aspirin (log-rank test; P=0.01). In conclusion, aPL-positive SLE and AIT patients should take aspirin to prevent APS manifestations. Prospective therapeutic trials are needed to confirm aspirin's prophylactic role in such patients.
Subject(s)
Antibodies, Anticardiolipin/blood , Antiphospholipid Syndrome/drug therapy , Aspirin/therapeutic use , Fibrinolytic Agents/therapeutic use , Lupus Coagulation Inhibitor/blood , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Thrombosis/prevention & control , Adult , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/immunology , Antiphospholipid Syndrome/mortality , Disease Progression , Female , Follow-Up Studies , Humans , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/mortality , Male , Middle Aged , Purpura, Thrombocytopenic, Idiopathic/complications , Purpura, Thrombocytopenic, Idiopathic/immunology , Purpura, Thrombocytopenic, Idiopathic/mortality , Retrospective Studies , Thrombosis/immunology , Thrombosis/mortality , Time Factors , Treatment OutcomeSubject(s)
Autoimmunity , Melanoma/secondary , Adult , Aged , Autoantibodies/blood , Disease Progression , Female , Humans , Male , Middle Aged , PrognosisABSTRACT
OBJECTIVE: Some studies have highlighted the potential benefits of switching from infliximab to etanercept, or after failure of one or the other treatment. To our knowledge, no study has assessed the potential benefits of using the three anti-TNF-alpha agents that are currently available. The objective of this retrospective study was to assess the response to treatment in RA patients who had received the three anti-TNF-alpha agents, namely infliximab, etanercept and adalimumab. METHODS: Among a cohort of 364 patients undergoing biological treatments since the year 2000, 284 had been treated with only one anti-TNF-alpha agent. Our assessment focused on the records of 70 patients who had received at least two anti-TNF-alpha agents. Twenty of the 70 patients had received all three anti-TNF-alpha agents (infliximab, etanercept and adalimumab). Effectiveness was assessed using the 28-joint Disease Activity Score (DAS28), and adverse events were reported for each anti-TNF-alpha treatment. RESULTS: Of the 70 patients who had received two anti-TNF-alpha agents, 32 had switched from an antibody to a soluble receptor; 45% of them had a good clinical response to the soluble receptor. Thirty patients had switched from a soluble receptor to an antibody; 45% of them had a good clinical response to the antibody. Only eight patients had switched from an antibody to another antibody with an efficiency score of 33%. Of the 20 patients who had received three anti-TNF-alpha agents, seven had stopped receiving the third anti-TNF-alpha agent due to lack of effectiveness. In this group of non-responders to the third anti-TNF-alpha treatment, all patients except one had stopped receiving the two previous anti-TNF-alpha agents, without adverse events, for lack of effectiveness. These patients were deemed resistant to anti-TNF-alpha therapy. CONCLUSIONS: Resistance to anti-TNF-alpha agents is rare. The lack of effectiveness of a soluble receptor and of one of the anti-TNF-alpha antibodies predicts the lack of effectiveness of the third anti-TNF-alpha treatment.
Subject(s)
Arthritis, Rheumatoid/drug therapy , Immunologic Factors/administration & dosage , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Drug Administration Schedule , Drug Therapy, Combination , Etanercept , Female , Humans , Immunoglobulin G/administration & dosage , Immunoglobulin G/therapeutic use , Immunologic Factors/therapeutic use , Infliximab , Male , Middle Aged , Receptors, Tumor Necrosis Factor/administration & dosage , Receptors, Tumor Necrosis Factor/therapeutic use , Retrospective Studies , Statistics, Nonparametric , Treatment FailureABSTRACT
INTRODUCTION: Over the last years, the functions of the immune system have radically been revised. It has been illustrated how the different responses of the innate defense and the adaptative system were intimately intricated. STATE OF KNOWLEDGE: Innate immunity is an elaborate strategy, switched on by an invariant receptor-based response that is able to develop a specific defense against some pathogens. Moreover, this innate immunity governs T- and B-cell-dependent adaptive immune response, mediated via dendritic cells whose maturation is controlled by immune specificity. The concepts of autoreactivity have also strongly progressed and the functions of the physiological autoimmune response have been highlighted. The notion of T- and B-cell self-antigens not only shapes the immune repertoire, but also the self-recognition process which is a tool for the control of the immune response itself. PERSPECTIVE: New concepts of the pathophysiology of autoimmune diseases have emerged from a better understanding of the immune response, balancing between an intrinsic deregulation of the immune system and system deficiency to mount an effective response against an initial injury. CONCLUSION: Of course, therapeutic strategies are challenged by these data. We should expect that control of several autoimmune processes will be achieved in a few years, e.g. in rheumatoid arthritis or Crohn's disease controlled with biotherapies.
Subject(s)
Autoimmune Diseases/immunology , Autoimmunity , Nervous System Diseases/immunology , Autoimmunity/physiology , Humans , Immunity, Innate , Inflammation/immunologyABSTRACT
INTRODUCTION: In the past decade, intravenous immunoglobulins (IVIG) have been widely used and their administration has grown throughout the world. The current indications of IVIG in neurological diseases are discussed on the basis of the passed and current trials. Unlike other immuomodulatory agents, IVIG are well tolerated and have very few side effects and a good viral safety. STATE OF ART: There is clinical evidence, based on controlled trials, for the effectiveness of IVIG in Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy and multifocal neuropathy with conduction blocks. In myasthenia gravis, the IVIG are effective especially in myasthenic crisis, but their synergistic effect with other treatments, the steroid sparing effect, and their long-term effect are unknown. These issues need to be addressed in further controlled clinical trials. In dermatoploymyositis, IVIG are reserved for steroid resistant patients. There is actually no support or no significant clinical benefit for the routine use of IVIG in other neurological diseases. PERSPECTIVES: Further controlled trials are warranted to assess the quality of life, the dose-finding effect and their long-term efficacy in order to improve clinical practices. CONCLUSION: Routine use of IVIG should be reserved for diseases in which positive controlled trials are available. For the remaining dysimmune diseases, IVIG should be assess in comparison with the other available therapies, taking into consideration the age of the patients, the safety of the IVIG and, in our country, the economic aspect.