RESUMEN
Fabry disease (FD) is an X-linked disease characterized by an accumulation of glycosphingolipids, notably of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lysoGb3) leading to renal failure, cardiomyopathy, and cerebral strokes. Inflammatory processes are involved in the pathophysiology. We investigated the immunological phenotype of peripheral blood mononuclear cells in Fabry patients depending on the clinical phenotype, treatment, Gb3, and lysoGb3 levels and the presence of anti-drug antibodies (ADA). Leucocytes from 41 male patients and 20 controls were analyzed with mass cytometry using both unsupervised and supervised algorithms. FD patients had an increased expression of CD27 and CD28 in memory CD45- and CD45 + CCR7-CD4 T cells (respectively p < 0.014 and p < 0.02). Percentage of CD45RA-CCR7-CD27 + CD28+ cells in CD4 T cells was correlated with plasma lysoGb3 (r = 0.60; p = 0.0036) and phenotype (p < 0.003). The correlation between Gb3 and CD27 in CD4 T cells almost reached significance (r = 0.33; p = 0.058). There was no immune profile associated with the presence of ADA. Treatment with agalsidase beta was associated with an increased proportion of Natural Killer cells. These findings provide valuable insights for understanding FD, linking Gb3 accumulation to inflammation, and proposing new prognostic biomarkers.
Asunto(s)
Linfocitos T CD4-Positivos , Enfermedad de Fabry , Trihexosilceramidas , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral , Humanos , Enfermedad de Fabry/inmunología , Masculino , Trihexosilceramidas/metabolismo , Adulto , Linfocitos T CD4-Positivos/inmunología , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/metabolismo , Persona de Mediana Edad , Adulto Joven , Adolescente , Esfingolípidos/metabolismo , Estudios de Casos y Controles , Antígenos Comunes de Leucocito , Células T de Memoria/inmunología , Células T de Memoria/metabolismo , Citometría de Flujo , Antígenos CD28 , Memoria Inmunológica , Receptores CCR7/metabolismo , GlucolípidosRESUMEN
OBJECTIVES: Hand involvement in patients with systemic sclerosis (SSc) is responsible for 75% of the overall disability but varies greatly among individuals. No study has yet compared the functionalities between the two hands of SSc patients. We thus evaluated the joint limitations and extent of skin involvement in the dominant and contralateral hands. METHODS: This prospective, descriptive, comparative single-centre study enrolled SSc patients diagnosed using the ACR/EULAR criteria. We assessed limitations in the joint range of motion during active and passive mobilisation; the first commissure opening angles; the Kapandji scale and Rodnan hand scores; the digital pressures; the finger brachial pressure indices; and the number of telangiectasias, calcinosis, digital ulcerations, and painful joints on each hand. RESULTS: Thirty patients were included. Spontaneous flexion joint limitations were significantly greater in the dominant hand (p<0.0001). The Kapandji score was lower (p<0.001) and the Rodnan hand score significantly higher, for the dominant hand (p<0.001). The digital pressure was similar between the hands. CONCLUSIONS: The dominant hand exhibited significantly more skin sclerosis and mean flexion deterioration, a lower Kapandji score, and a tendency toward reduced mean extension, compared with the other hand. No vascular pathology was noted in either hand. Larger studies are needed to confirm these results and to draw therapeutic conclusions.
Asunto(s)
Evaluación de la Discapacidad , Rango del Movimiento Articular , Esclerodermia Sistémica , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Prospectivos , Esclerodermia Sistémica/fisiopatología , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnóstico , Anciano , Adulto , Mano/fisiopatología , Índice de Severidad de la Enfermedad , Telangiectasia/fisiopatología , Telangiectasia/etiología , Piel/patología , Piel/irrigación sanguínea , Articulaciones de la Mano/fisiopatología , Estado FuncionalRESUMEN
OBJECTIVES: Giant cell arteritis (GCA) often features upper respiratory tract (URT) and orofacial manifestations, which signal the involvement of external carotid artery branches. In this study, we aimed to describe the frequency of various URT/orofacial symptoms at GCA onset, as well as the main characteristics of patients presenting these symptoms. METHODS: We included all patients who were newly diagnosed with GCA between 1976 and April 2022 at the Internal Medicine Department of a tertiary-care hospital. Ten URT or orofacial symptoms were prospectively examined systematically in each patient. We used multivariate analyses to identify the GCA characteristics, including URT/orofacial symptoms, associated with temporal artery biopsy (TAB) positivity. RESULTS: At least 1 URT/orofacial symptom was present in 68.6% of the 599 patients (3 or more symptoms in 30% of cases). Jaw claudication, maxillary pain, and pain during mouth opening were the most prevalent symptoms. Dry cough was recorded in 17% of cases. GCA patients with URT/orofacial symptoms had more clinical abnormalities of the temporal artery bed and ischaemic ophthalmological complications, but less large-vessel vasculitis according to imaging. The likelihood of a positive TAB was increased in patients with an abnormal temporal artery upon clinical examination (OR 4.16; CI 2.75-6.37, p < 0.001) or jaw claudication (OR 2.18; CI 1.35-3.65, p = 0.002), and decreased in those with hoarseness (OR 0.47; CI 0.26-0.87, p = 0.02) or earache (OR 0.54; CI 0.31-0.95, p = 0.03). Isolated URT/orofacial presentation (i.e., without headache or visual signs) accounted for 5.2% of the entire cohort. CONCLUSIONS: Oral-facial symptoms were present in two-thirds of GCS cases. Thus, they could serve as leading clinical clues for a GCA diagnosis, and are a risk factor for permanent visual loss. Several URT/orofacial symptoms such as jaw claudication, hoarseness, and earache influenced the likelihood of a positive TAB. Isolated URT/orofacial presentation of GCA is a rare but potentially challenging occurrence.
RESUMEN
OBJECTIVES: To describe the characteristics of 18F-fluorodeoxyglucose positron-emission tomography/computed-tomography (18FDG-PET/CT) findings before surgery in patients with active, histologically confirmed aortitis, and to correlate the degree of arterial wall inflammation with PETVAS score. METHODS: This was a multiple-centre retrospective study including cases with histologically proven active, non-infectious aortitis who had a 18FDG-PET/CT performed within one year before surgery for aneurysm repair. PETVAS score was determined by radiologists blinded to the pathology findings. Cardiovascular pathologists reviewed aortic tissue samples and graded the degree of inflammation in the vessel wall. RESULTS: Sixteen patients were included (8 giant cell arteritis, 4 clinically isolated aortitis, 2 Takayasu's arteritis, 1 relapsing polychondritis, and 1 rheumatoid arthritis). In 5/16 (31%) patients, 18FDG-PET/CT did not detect the presence of aortic inflammation; two of whom were being treated with glucocorticoids at the time of procedure. Ascending thoracic and abdominal aorta had the highest FDG uptake among the affected territories. Patients without active aortitis on 18FDG-PET/CT were significantly older (p=0.027), had a lower PETVAS score (p=0.007), and had a lower degree of adventitial inflammation (p=0.035). In contrast, there was no difference between 18FDG-PET/CT active and inactive aortitis patients as regards the timing between PET/CT and surgery, serum CRP level (during 18FDG-PET/CT) and, FDG uptake per study site. CONCLUSIONS: In histologically proved aortitis, 18FDG-PET/CT before surgery did not detect vascular inflammation in 31% patients, and PETVAS score correlated with the degree of adventitial histopathologic inflammation.
Asunto(s)
Aortitis , Humanos , Aortitis/diagnóstico por imagen , Aortitis/etiología , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Retrospectivos , Radiofármacos , Tomografía de Emisión de Positrones/métodos , Aorta Abdominal , InflamaciónRESUMEN
INTRODUCTION: Biopsy-proven giant cell arteritis (GCA) occasionally presents without acute-phase reaction. In this setting, GCA may be initially overlooked and glucocorticoid treatment unduly delayed, potentially increasing ischemic risk. PATIENTS AND METHODS: From an inception cohort of patients with newly diagnosed, biopsy-verified GCA, we retrieved all cases without elevation of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level before starting glucocorticoid treatment. We compared the baseline features and outcomes of these patients and two additional patients recruited after GCA diagnosis with those of 42 randomly selected patients with high baseline ESR and CRP. RESULTS: Of 396 patients, 14 (3.5%) had lower baseline values of both ESR and CRP. Lower baseline ESR and CRP were associated with fewer American College of Rheumatology criteria met (p < 0.001, 95% CI - 1.1; - 0.9), and less jaw claudication (p = 0.06, 95% CI 0.8; 44.9), but similar rates of permanent blindness (p = 1.0). Patients with lower ESR and CRP also showed obvious differences regarding mean blood cell counts and mean hemoglobin level, but also less anti-cardiolipin antibody positivity (p = 0.04, 95% CI 0.8; ∞) and hepatic cholestasis (p = 0.03, 95% CI 1.0; 422). Patients with lower ESR and CRP had fewer GCA relapses (p = 0.03, 95% CI - 1.1; - 0.1), fewer glucocorticoid-induced complications (p = 0.01, 95% CI - 2.0; - 0.1), and successfully stopped glucocorticoids sooner than the other patients (18.3 months vs 34 months in average, p = 0.02, 95% CI - 27;- 0.9). CONCLUSION: Biopsy-proven GCA presenting with lower ESR and CRP is not an exceptional occurrence. It is clinically less typical but carries similar ischemic risk to other forms of the disease. Conversely, the late GCA prognosis of these patients is excellent.
Asunto(s)
Arteritis de Células Gigantes , Humanos , Arteritis de Células Gigantes/complicaciones , Arteritis de Células Gigantes/tratamiento farmacológico , Arteritis de Células Gigantes/diagnóstico , Sedimentación Sanguínea , Glucocorticoides/uso terapéutico , Estudios de Casos y Controles , Proteína C-Reactiva/análisisRESUMEN
OBJECTIVES: New permanent visual loss (PVL) in treated patients with giant cell arteritis (GCA) is a rare but worrisome occurrence. In this study, we aimed to describe the frequency and main features of new PVL occurring after the beginning of glucocorticoid therapy in patients with newly diagnosed GCA. METHODS: We included in an inception cohort all consecutive patients newly diagnosed with GCA in the internal medicine department of a tertiary-care hospital between 1976 and May 2020. The study population comprised all the patients without bilateral PVL before treatment who were followed for at least one year. Only well-documented visual events that set after the initiation of glucocorticoid treatment were regarded as new PVL. RESULTS: Eleven out of 502 patients (2.2%) experienced a new PVL including 6 occurrences during the initial therapeutic phase and 5 during the tapering phase. Patients with new PVL during treatment had higher mean age, more often displayed temporal artery abnormalities on physical examination, and had higher mean platelet counts at GCA onset. There was a strong excess risk of contralateral recurrence during treatment in patients with unilateral loss at GCA onset compared with patients with uncomplicated GCA (10.5% vs 1.1%, OR=10.26, p<0.001). CONCLUSIONS: New PVL in treated GCA is a rare, but significant occurrence. Older patients and patients who already had unilateral PVL at diagnosis have higher risk of new ischaemic visual loss during treatment compared to the other patients. Close clinical, laboratory, and eye monitoring of these high-risk patients is of paramount importance.
Asunto(s)
Arteritis de Células Gigantes , Ceguera , Arteritis de Células Gigantes/complicaciones , Arteritis de Células Gigantes/diagnóstico , Arteritis de Células Gigantes/tratamiento farmacológico , Glucocorticoides/efectos adversos , Humanos , Estudios Retrospectivos , Factores de Riesgo , Arterias Temporales , Trastornos de la Visión/epidemiología , Trastornos de la Visión/etiologíaRESUMEN
OBJECTIVES: The treatment of GCA relies on corticosteroids but is burdened by a high rate of relapses and adverse effects. Anti-IL-6 treatments show a clear benefit with a significant steroid-sparing effect, but late relapses occur after treatment discontinuation. In addition to IL-6, IL-1 also appears to play a significant role in GCA pathophysiology. We report herein the efficacy of anakinra, an IL-1 receptor antagonist, in six GCA patients exhibiting corticosteroid dependence or resistance, specifically analysing the outcome of aortitis in four of them. METHODS: This retrospective study analysed the cases of all GCA patients treated with anakinra from the French Study Group for Large Vessel Vasculitis. RESULTS: After a median duration of anakinra therapy of 19 (18-32) months, all six patients exhibited complete clinical and biological remission. Among the four patients with large-vessel involvement, one had a disappearance of aortitis under anakinra and three showed a decrease in vascular uptake. After a median follow-up of 56 (48-63) months, corticosteroids were discontinued in four patients, and corticosteroid dosage could be decreased to 5 mg/day in two patients. One patient relapsed 13 months after anakinra introduction in the context of increasing the daily anakinra injection interval to every 48 h. Three patients experienced transient injection-site reactions, and one patient had pneumonia. CONCLUSION: In this short series, anakinra appears to be an efficient and safe steroid-sparing agent in refractory GCA, with a possible beneficial effect on large-vessel involvement.
Asunto(s)
Corticoesteroides/uso terapéutico , Antirreumáticos/uso terapéutico , Arteritis de Células Gigantes/tratamiento farmacológico , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Anciano , Femenino , Humanos , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Giant cell arteritis (GCA) is a systemic vasculitis of large and medium vessels characterized by an inflammatory arterial infiltrate. GCA begins in the adventitia and leads to vascular remodeling by promoting proliferation of myofibroblasts in the intima. The morphology of the fibroblasts in the adventitia in GCA is unclear. Access to temporal artery biopsies allows morphological studies and evaluation of the microenvironment of the arterial wall. We evaluated the distribution of vascular fibroblasts and of markers of their activation in GCA. METHODS: Formalin-fixed paraffin-embedded tissue sections from 29 patients with GCA and 36 controls were examined. Immunohistochemistry was performed for CD90, vimentin, desmin, alpha-smooth muscle actin (ASMA), prolyl-4-hydroxylase (P4H), and myosin to evaluate the distribution of fibroblasts within the intima, media, and adventitia. RESULTS: Temporal arteries from patients with GCA showed increased levels of CD90, vimentin, and ASMA in the adventitia and intima compared to the controls. Desmin was expressed only in the media in both groups. P4H was expressed similarly in the adventitia and intima in the two groups. Adventitial and intimal CD90+ cells co-expressed P4H, ASMA, and myosin at a high level in GCA. CONCLUSION: The results suggest a role for adventitial fibroblasts in GCA. Inhibiting the differentiation of adventitial fibroblasts to myofibroblasts has therapeutic potential for GCA.
Asunto(s)
Fibroblastos/metabolismo , Arteritis de Células Gigantes/patología , Inmunohistoquímica/métodos , Arterias Temporales/patología , Actinas/metabolismo , Adventicia/metabolismo , Anciano , Biomarcadores/metabolismo , Biopsia , Estudios de Casos y Controles , Proliferación Celular , Desmina/metabolismo , Femenino , Arteritis de Células Gigantes/diagnóstico , Arteritis de Células Gigantes/fisiopatología , Humanos , Masculino , Arterias Temporales/metabolismo , Antígenos Thy-1/metabolismo , Microambiente Tumoral , Túnica Íntima/metabolismo , Remodelación Vascular , Vimentina/metabolismoRESUMEN
OBJECTIVE: The aims of this study were to describe and assess the vascular outcomes of patients with giant cell arteritis (GCA) presenting with only symptomatic isolated limb involvement (LI-GCA). METHODS: We recruited patients from 5 tertiary centers who were diagnosed with GCA based on histology or vasculitis demonstration on imaging and who presented with isolated symptomatic limb involvement at diagnosis. For each included patient, we randomly selected 3 control patients who satisfied the 5 criteria from the American College of Rheumatology at diagnosis. RESULTS: We included 27 LI-GCA patients and 81 control patients. Compared with the controls, the patients with LI-GCA were younger (p = 0.005), exhibited a more delayed diagnosis (p = 0.006), and had lower C-reactive protein levels (p = 0.001), but they did not show more cardiovascular risk factors. Glucocorticoid use (starting and tapering doses) and relapse rates did not differ in the 2 groups, but the patients with LI-GCA received longer treatment (p = 0.02). Cardiovascular complications occurred in 67% of the patients with LI-GCA versus 21% of the control patients (p < 0.0001), especially ischemic events (p < 0.0001) including stroke (p = 0.03) and myocardial infarction (p = 0.01). Vascular surgery was required in 44% of the patients with LI-GCA versus 2% of the controls (p < 0.0001). Excluding vascular surgery, the cumulative incidence of cardiovascular complications was higher in the patients with LI-GCA (log-rank test: p < 0.0001) than in the controls (hazard ratio, 5.73; 95% confidence interval, 2.94-11.28; p < 0.0001). CONCLUSIONS: Compared with the typical cranial form of GCA, LI-GCA has a worse cardiovascular-related prognosis. Further studies are required to determine the best management of these patients.
Asunto(s)
Arteritis de Células Gigantes , Accidente Cerebrovascular , Arteritis de Células Gigantes/complicaciones , Arteritis de Células Gigantes/diagnóstico , Arteritis de Células Gigantes/tratamiento farmacológico , Glucocorticoides , Humanos , Pronóstico , Estudios RetrospectivosRESUMEN
Large-vessel involvement (LVI) in giant cell arteritis (GCA) includes different clinical and imaging patterns that are rarely described separately at diagnosis and whose specific cardiovascular outcomes are unknown. We conducted a nationwide retrospective study and included GCA patients with LVI demonstrated on imaging at diagnosis between 2007 and 2017. We analyzed the prognosis of three different imaging patterns of LVI present at diagnosis, with some of them overlapping but with the first one present in all patients: 1) inflammation of the aorta and/or its branches; 2) dilation of the aorta; and 3) stenosis of the aortic branches. A control group of GCA patients without LVI was constituted. We included 183 patients with LVI and 105 controls without LVI. Altogether, among the 183 patients who all showed inflammation of the aorta and/or its main branches, concomitant aortic dilation and large-vessel stenosis were observed in 27 (15%) and 55 (30%) patients, respectively. During the follow-up period, new cardiovascular events occurred in 49% and 11% of LVI patients and controls, respectively (pâ¯<â¯0.0001). Inflammation of the aorta and/or its branches (HR: 3.42 [2.09-5.83], pâ¯<â¯0.0001) and large-artery stenosis (HR: 2.75 [1.80-4.15], pâ¯<â¯0.0001) were independent predictive factors of new cardiovascular events. Conversely, the use of an immunosuppressant besides corticosteroids was a protective factor against new cardiovascular events (HR: 0.44 [0.29-0.66], pâ¯<â¯0.0001) and the development of aortic dilation (HR: 0.43 [0.23-0.77], pâ¯=â¯0.005). This study suggests different forms of cardiovascular events according to the initial imaging pattern of LVI.
Asunto(s)
Aorta/patología , Enfermedades Cardiovasculares/diagnóstico , Diagnóstico por Imagen/métodos , Arteritis de Células Gigantes/diagnóstico , Inflamación/diagnóstico , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/epidemiología , Constricción Patológica , Femenino , Estudios de Seguimiento , Francia/epidemiología , Arteritis de Células Gigantes/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVES: To estimate the frequency of different clinical patterns in giant-cell arteritis (GCA) at onset. METHODS: All GCA patients consecutively followed-up in two referral centers for GCA with a biopsy-proven diagnosis and/or large-vessel vasculitis (LVV) demonstrated on imaging were analysed. RESULTS: We analysed the initial clinical presentation of 693 patients with a median age of 75 [48-94] years and including 486 (70%) women. We identified four different clinical patterns: isolated cranial GCA (in 80%), symptomatic LVV with or without associated cranial signs (9%), isolated fever or inflammatory response (9%), and isolated polymyalgia rheumatica with vasculitis (2%). A silent LVV was found in 110 (45%) out of the 247 patients without large-vessel symptoms who underwent imaging at GCA diagnosis. Symptomatic LVV patients were more frequently GC-dependent compared to other patterns (p=0.03) and showed the longest treatment duration (median: 37 [15-212] months versus <30 months for other clinical phenotypes; p=0.001). CONCLUSIONS: This study suggests that 80% of GCA patients display a typical presentation, whereas the other 20% showed rarer presentations. Patients with symptomatic LVV required longer treatment duration.
Asunto(s)
Arteritis de Células Gigantes , Polimialgia Reumática , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Arteritis de Células Gigantes/diagnóstico , Arteritis de Células Gigantes/patología , Humanos , Masculino , Persona de Mediana Edad , FenotipoRESUMEN
PURPOSE: The purpose of our study was to assess the concordance of aortic CT angiography (CTA) and FDG-PET/CT in the detection of large-vessel involvement at diagnosis in patients with giant-cell arteritis (GCA). METHODS: We created a multicenter cohort of patients with GCA diagnosed between 2010 and 2015, and who underwent both FDG-PET/CT and aortic CTA before or in the first ten days following treatment introduction. Eight vascular segments were studied on each procedure. We calculated concordance between both imaging techniques in a per-patient and a per-segment analysis, using Cohen's kappa concordance index. RESULTS: We included 28 patients (21/7 women/men, median age 67 [56-82]). Nineteen patients had large-vessel involvement on PET/CT and 18 of these patients also presented positive findings on CTA. In a per-segment analysis, a median of 5 [1-7] and 3 [1-6] vascular territories were involved on positive PET/CT and CTA, respectively (p = 0.03). In qualitative analysis, i.e., positivity of the procedure suggesting a large-vessel involvement, the concordance rate between both procedures was 0.85 [0.64-1]. In quantitative analysis, i.e., per-segment analysis in both procedures, the global concordance rate was 0.64 [0.54-0.75]. Using FDG-PET/CT as a reference, CTA showed excellent sensitivity (95%) and specificity (100%) in a per-patient analysis. In a per-segment analysis, sensitivity and specificity were 61% and 97.9%, respectively. CONCLUSIONS: CTA and FDG-PET/CT were both able to detect large-vessel involvement in GCA with comparable results in a per-patient analysis. However, PET/CT showed higher performance in a per-segment analysis, especially in the detection of inflammation of the aorta's branches.
Asunto(s)
Aorta/diagnóstico por imagen , Angiografía por Tomografía Computarizada , Fluorodesoxiglucosa F18 , Arteritis de Células Gigantes/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
OBJECTIVES: To analyse the 10-year outcomes of 64 patients with non-HBV polyarteritis nodosa (PAN) or microscopic polyangiitis (MPA) and Five-Factor Score-defined poor-prognosis factors enrolled (1994-2000) in the prospective, randomised, open-label CHUSPAN trial. METHODS: The 64 patients were randomised to receive 12 (33: 23 MPA, 10 PAN) or 6 (31: 17 MPA, 14 PAN) cyclophosphamide (CYC) pulses combined with glucocorticoids. Ten-year follow-up of these patients included times to relapse(s), failure(s) and/or deaths calculated from treatment onset. Data were censored after 120 months of follow-up. RESULTS: Eleven patients were lost to-follow-up (mean±SD follow-up: 61.9±35.2 months), with no between-group difference. As previously reported, baseline clinical characteristics and laboratory values were comparable for the 2 groups. After induction, 53/64 (83%) entered remission, with comparable percentages for both groups. The regimen was intensified for 11 initial non-responders: 4 achieved remission and 8 died before doing so. During extended follow-up, 26 patients experienced ≥1 relapse(s): 12 in the 12-pulse group and 14 in the 6-pulse group (p=0.47). At 10 years, overall and disease-free survival rates were 57.4% and 29.9%, with no between-group differences (p=0.185 and p=0.367, respectively). Factors associated with shorter disease-free survival were age ≥65 years and alveolar haemorrhage at diagnosis. CONCLUSIONS: Although the 3-year CHUSPAN trial results indicated the superiority of 12 vs. 6 CYC pulses, that early advantage progressively declined and became non-significant by 10 years.
Asunto(s)
Ciclofosfamida/administración & dosificación , Glucocorticoides/administración & dosificación , Inmunosupresores/administración & dosificación , Poliangitis Microscópica/tratamiento farmacológico , Poliarteritis Nudosa/tratamiento farmacológico , Adulto , Anciano , Bélgica , Ciclofosfamida/efectos adversos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Quimioterapia Combinada , Femenino , Francia , Glucocorticoides/efectos adversos , Humanos , Inmunosupresores/efectos adversos , Masculino , Poliangitis Microscópica/diagnóstico , Poliangitis Microscópica/mortalidad , Persona de Mediana Edad , Poliarteritis Nudosa/diagnóstico , Poliarteritis Nudosa/mortalidad , Estudios Prospectivos , Quimioterapia por Pulso , Recurrencia , Inducción de Remisión , Factores de Tiempo , Resultado del TratamientoRESUMEN
Vascular smooth muscle cells (VSMCs) are highly specialized cells that regulate vascular tone and participate in vessel remodeling in physiological and pathological conditions. It is unclear why certain vascular pathologies involve one type of vessel and spare others. Our objective was to compare the proteomes of normal human VSMC from aorta (human aortic smooth muscle cells, HAoSMC), umbilical artery (human umbilical artery smooth muscle cells, HUASMC), pulmonary artery (HPASMC), or pulmonary artery VSMC from patients with pulmonary arterial hypertension (PAH-SMC). Proteomes of VSMC were compared by 2D DIGE and MS. Only 19 proteins were differentially expressed between HAoSMC and HPASMC while 132 and 124 were differentially expressed between HUASMC and HAoSMC or HPASMC, respectively (fold change 1.5≤ or -1.5≥, p < 0.05). As much as 336 proteins were differentially expressed between HPASMC and PAH-SMC (fold change 1.5≤ or -1.5≥, p < 0.05). HUASMC expressed increased amount of α-smooth muscle actin compared to either HPASMC or HAoSMC (although not statistically significant). In addition, PAH-SMC expressed decreased amount of smooth muscle myosin heavy chain and proliferation rate was increased compared to HPASMC thus supporting that PAH-SMC have a more synthetic phenotype. Analysis with Ingenuity identified paxillin and (embryonic lethal, abnormal vision, drosophila) like 1 (ELAVL1) as molecules linked with a lot of proteins differentially expressed between HPASMC and PAH-SMC. There was a trend toward reduced proliferation of PAH-SMC with paxillin-si-RNA and increased proliferation with ELAVL1-siRNA. Thus, VSMCs have very diverse protein content depending on their origin and this is in link with phenotypic differentiation. Paxillin targeting may be a promising treatment of PAH. ELAVL1 also participate in the regulation of PAH-SMC proliferation.
Asunto(s)
Hipertensión Pulmonar/patología , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/patología , Mapas de Interacción de Proteínas , Proteoma/análisis , Arteria Pulmonar/patología , Proliferación Celular , Células Cultivadas , Proteína 1 Similar a ELAV/genética , Proteína 1 Similar a ELAV/metabolismo , Regulación de la Expresión Génica , Humanos , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Paxillin/genética , Paxillin/metabolismo , Proteoma/genética , Proteoma/metabolismo , Arteria Pulmonar/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/genéticaRESUMEN
CD8(+) T cells participate in the pathogenesis of some vasculitides. However, little is known about their role in Giant Cell Arteritis (GCA). This study was conducted to investigate CD8(+) T cell involvement in the pathogenesis of GCA. Analyses were performed at diagnosis and after 3 months of glucocorticoid treatment in 34 GCA patients and 26 age-matched healthy volunteers. Percentages of CD8(+) T-cell subsets, spectratype analysis of the TCR Vß families of CD8(+) T cells, levels of cytokines and chemokines and immunohistochemistry of temporal artery biopsies (TAB) were assessed. Among total CD8(+) T cells, percentages of circulating cytotoxic CD8 T lymphocytes (CTL, CD3(+)CD8(+)perforin(+)granzymeB(+)), Tc17 (CD3(+)CD8(+)IL-17(+)), CD63(+)CD8(+) T cells and levels of soluble granzymes A and B were higher in patients than in controls, whereas the percentage of Tc1 cells (CD3(+)CD8(+)IFN-γ(+)) was similar. Moreover, CD8(+) T cells displayed a restricted TCR repertoire in GCA patients. Percentages of circulating CTL, Tc17 and soluble levels of granzymes A and B decreased after treatment. CXCR3 expression on CD8(+) T cells and its serum ligands (CXCL9, -10, -11) were higher in patients. Analyses of TAB revealed high expression of CXCL9 and -10 associated with infiltration by CXCR3(+)CD8(+) T cells expressing granzyme B and TiA1. The intensity of the CD8 T-cell infiltrate in TAB was predictive of the severity of the disease. This study demonstrates the implication and the prognostic value of CD8(+) T-cells in GCA and suggests that CD8(+) T-cells are recruited within the vascular wall through an interaction between CXCR3 and its ligands.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Citocinas/inmunología , Arteritis de Células Gigantes/inmunología , Anciano , Anciano de 80 o más Años , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/metabolismo , Células Cultivadas , Quimiocina CXCL10/inmunología , Quimiocina CXCL10/metabolismo , Quimiocina CXCL11/inmunología , Quimiocina CXCL11/metabolismo , Quimiocina CXCL9/inmunología , Quimiocina CXCL9/metabolismo , Citocinas/metabolismo , Femenino , Arteritis de Células Gigantes/tratamiento farmacológico , Arteritis de Células Gigantes/metabolismo , Glucocorticoides/uso terapéutico , Granzimas/inmunología , Granzimas/metabolismo , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Prednisona/uso terapéutico , Pronóstico , Estudios Prospectivos , Receptores CXCR3/inmunología , Receptores CXCR3/metabolismoRESUMEN
BACKGROUND: Complementary and alternative medicine (CAM) is composed of a wide range of interventions and frequently used in parallel with conventional medicine. The aim of this study was to assess the prevalence, modalities, and association factors of CAM utilization in patients treated for systemic lupus erythematosus, primary Sjögren's syndrome, or systemic sclerosis. PATIENTS AND METHODS: This was a prospective single-center observational study conducted in a French university hospital center. Inclusion criteria were patients followed for systemic lupus erythematosus, primary Sjögren's syndrome, or systemic sclerosis. Data were collected with a survey which assessed sociodemographic, disease characteristics, CAM use details, life quality, and anxiety score. RESULTS: A total of 121 patients were included, mostly women (87%), with an average age of 56 years. Proportion of patients seeking CAM was 55%. A total of 186 CAM interventions were recorded: most common were osteopathy, homeopathy, and acupuncture. Patients were looking for well-being (22%), reducing their fatigue (18%) and pain (33%). Concerning physical and mental feeling after CAM use, a subjective improvement was reported in 89% of cases. In multivariate analysis, CAM use by patient was associated with these 3 variables: coming from a Western culture, being professionally active, and having a poor quality of life and anxiety scores. CONCLUSION AND OUTLOOK: This is the first study to focus on CAM use in patients followed for three AID in a French rural region. The current challenge is to enrich conventional medicine with CAM that is effective and safe through supervised programs to move toward an integrative medicine.
Asunto(s)
Terapias Complementarias , Lupus Eritematoso Sistémico , Esclerodermia Sistémica , Síndrome de Sjögren , Humanos , Femenino , Síndrome de Sjögren/terapia , Persona de Mediana Edad , Masculino , Terapias Complementarias/estadística & datos numéricos , Esclerodermia Sistémica/terapia , Lupus Eritematoso Sistémico/terapia , Francia , Estudios Prospectivos , Adulto , Anciano , Población Rural , Calidad de VidaRESUMEN
BACKGROUND: Angioedema (AE) due to acquired C1-inhibitor (C1-INH) deficiency (AAE-C1-INH) is related to excessive consumption of C1-INH or to anti-C1-INH antibodies, and is frequently associated with lymphoproliferative syndromes or monoclonal gammopathies. Standard of care for prophylactic treatment in this condition is not established. Rituximab may be effective to prevent attacks, especially if the lymphoid hemopathy is controlled, but data are scarce. OBJECTIVE: To evaluate efficacy of rituximab in AAE-C1-INH. METHODS: A retrospective multicenter study was carried out in France, including patients with AAE-C1-INH treated with rituximab between April 2005 and July 2019. RESULTS: Fifty-five patients with AAE-C1-INH were included in the study, and 23 of them had an anti-C1-INH antibody. A lymphoid malignancy was identified in 39 patients, and a monoclonal gammopathy in 9. There was no associated condition in 7 cases. Thirty patients received rituximab alone or in association with chemotherapy (n = 25). Among 51 patients with available follow-up, 34 patients were in clinical remission and 17 patients had active AE after a median follow-up of 3.9 years (interquartile range, 1.5-7.7). Three patients died. The presence of anti-C1-INH antibodies was associated with a lower probability of AE remission (hazard ratio, 0.29 [95% CI, 0.12-0.67]; P = .004). Relapse was less frequent in patients with lymphoma (risk ratio, 0.27 [95% CI, 0.09-0.80]; P = .019) and in patients treated with rituximab and chemotherapy (risk ratio, 0.31 [95% CI, 0.12-0.79]; P = .014). CONCLUSIONS: Rituximab is an efficient and well-tolerated therapeutic option in AE, especially in lymphoid malignancies and in the absence of detectable anti-C1-INH antibodies.
Asunto(s)
Angioedema , Angioedemas Hereditarios , Humanos , Angioedema/tratamiento farmacológico , Angioedemas Hereditarios/tratamiento farmacológico , Proteína Inhibidora del Complemento C1/genética , Francia , Estudios Retrospectivos , Rituximab/uso terapéuticoRESUMEN
INTRODUCTION: Giant cell arteritis (GCA) is complicated in 10 to 20% of cases by permanent visual ischemia (PVI). International guidelines advocate the use of intravenous pulse of methylprednisolone from 250 to 1000mg per day, for three days, followed by oral prednisone at 1mg/kg per day. The aim of this study is to assess whether this strategy significantly reduces the risk of early PVI of the second eye, compared with direct prednisone at 1mg/kg per day. METHODS: We conducted a multicentre retrospective observational study over the past 15 years in 13 French hospital centres. Inclusion criteria included: new case of GCA; strictly unilateral PVI, prednisone at dose greater than or equal to 0.9mg/kg per day; for the intravenous methylprednisolone (IV-MP) group, total dose between 900 and 5000mg, close follow-up and knowledge of visual status at 1 month of treatment, or earlier, in case of contralateral PVI. The groups were compared on demographic, clinical, biological, iconographic, and therapeutic parameters. Statistical analysis was optimised using propensity scores. RESULTS: One hundred and sixteen patients were included, 86 in the IV-MP group and 30 in the direct prednisone group. One patient in the direct prednisone group and 13 in the IV-MP group bilateralised, without significant difference between the two strategies (3.3% vs 15.1%). Investigation of the association between IV-MP patients and contralateral PVI through classical logistic regression, matching or stratification on propensity score did not show a significant association. Weighting on propensity score shows a significant association between IV-MP patients and contralateral PVI (OR=12.9 [3.4; 94.3]; P<0.001). Improvement in visual acuity of the initially affected eye was not significantly associated with IV-MP (visual acuity difference 0.02 vs -0.28 LogMar), even in the case of early management, i.e., within the first 48hours after the onset of PVI (n=61; visual acuity difference -0.11 vs 0.25 LogMar). Complications attributable to corticosteroid therapy in the first month were significantly more frequent in the IV-MP group (31.8 vs 10.7%; P<0.05). DISCUSSION: Our data do not support the routine use of pulse IV-MP for GCA complicated by unilateral PVI to avoid bilateral ophthalmologic damage. It might be safer to not give pulse IV-MP to selected patients with high risks of glucocorticoids pulse side effects. A prospective randomised multicentre study comparing pulse IV-MP and prednisone at 1mg/kg per day is desirable.
Asunto(s)
Arteritis de Células Gigantes , Metilprednisolona , Humanos , Arteritis de Células Gigantes/complicaciones , Arteritis de Células Gigantes/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Metilprednisolona/uso terapéutico , Prednisona/uso terapéutico , Puntaje de Propensión , Estudios RetrospectivosRESUMEN
Temporal artery biopsy (TAB) is a surgical procedure that enables the histological diagnosis of giant cell arteritis (GCA). Performing a TAB requires expertise and a precise approach. Nevertheless, available data supports the value of tissue diagnosis in managing GCA. The current therapeutic recommendation for GCA is long-term glucocorticoid therapy, with an increasing emphasis on the addition of immunosuppressants/biotherapies. Though effective, immunosuppressants and other such biotherapies may put the patient at more risk. Optimizing the diagnosis through tissue evaluation is therefore important in weighing the risks and benefits of initiating therapeutic intervention. We evaluate the evidence supporting the importance of TAB and its indications. We also describe what technical approaches should be used to maximize sensitivity and to avoid possible complications during the procedure.