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1.
Lancet Rheumatol ; 6(7): e447-e459, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38878780

RESUMEN

BACKGROUND: Systemic lupus erythematosus (SLE) is characterised by increased cardiovascular morbidity and mortality risk. We aimed to examine the prevalence of traditional cardiovascular risk factors and their control in an international survey of patients with systemic lupus erythematosus. METHODS: In this multicentre, cross-sectional study, cardiovascular risk factor data from medical files of adult patients (aged ≥18) with SLE followed between Jan 1, 2015, and Jan 1, 2020, were collected from 24 countries, across five continents. We assessed the prevalence and target attainment of cardiovascular risk factors and examined potential differences by country income level and antiphospholipid syndrome coexistence. We used the Systemic Coronary Risk Evaluation algorithm for cardiovascular risk estimation, and the European Society of Cardiology guidelines for assessing cardiovascular risk factor target attainment. People with lived experience were not involved in the research or writing process. FINDINGS: 3401 patients with SLE were included in the study. The median age was 43·0 years (IQR 33-54), 3047 (89·7%) of 3396 patients were women, 349 (10.3%) were men, and 1629 (48·1%) of 3390 were White. 556 (20·7%) of 2681 patients had concomitant antiphospholipid syndrome. We found a high cardiovascular risk factor prevalence (hypertension 1210 [35·6%] of 3398 patients, obesity 751 [23·7%] of 3169 patients, and hyperlipidaemia 650 [19·8%] of 3279 patients), and suboptimal control of modifiable cardiovascular risk factors (blood pressure [target of <130/80 mm Hg], BMI, and lipids) in the entire SLE group. Higher prevalence of cardiovascular risk factors but a better blood pressure (target of <130/80 mm Hg; 54·9% [1170 of 2132 patients] vs 46·8% [519 of 1109 patients]; p<0·0001), and lipid control (75·0% [895 of 1194 patients] vs 51·4% [386 of 751 patients], p<0·0001 for high-density lipoprotein [HDL]; 66·4% [769 of 1158 patients] vs 60·8% [453 of 745 patients], p=0·013 for non-HDL; 80·9% [1017 of 1257 patients] vs 61·4% [486 of 792 patients], p<0·0001 for triglycerides]) was observed in patients from high-income versus those from middle-income countries. Patients with SLE with antiphospholipid syndrome had a higher prevalence of modifiable cardiovascular risk factors, and significantly lower attainment of BMI and lipid targets (for low-density lipoprotein and non-HDL) than patients with SLE without antiphospholipid syndrome. INTERPRETATION: High prevalence and inadequate cardiovascular risk factor control were observed in a large multicentre and multiethnic SLE cohort, especially among patients from middle-income compared with high-income countries and among those with coexistent antiphospholipid syndrome. Increased awareness of cardiovascular disease risk in SLE, especially in the above subgroups, is urgently warranted. FUNDING: None.


Asunto(s)
Síndrome Antifosfolípido , Enfermedades Cardiovasculares , Factores de Riesgo de Enfermedad Cardiaca , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/complicaciones , Estudios Transversales , Masculino , Femenino , Adulto , Persona de Mediana Edad , Prevalencia , Enfermedades Cardiovasculares/epidemiología , Síndrome Antifosfolípido/epidemiología , Síndrome Antifosfolípido/complicaciones , Factores de Riesgo , Hipertensión/epidemiología
2.
Lupus ; 33(4): 340-346, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38334100

RESUMEN

BACKGROUND: Systemic lupus erythematosus (SLE) often mimics symptoms of other diseases, and the interval between symptom onset and diagnosis may be long in some of these patients. Aims: To describe the characteristics associated with the time to SLE diagnosis and its impact on damage accrual and mortality in patients with SLE from a Latin American inception cohort. METHODS: Patients were from a multi-ethnic, multi-national Latin-American SLE inception cohort. All participating centers had specialized lupus clinics. Socio-demographic, clinical/laboratory, disease activity, damage, and mortality between those with a longer and a shorter time to diagnosis were compared using descriptive statistical tests. Multivariable Cox regression models with damage accrual and mortality as the end points were performed, adjusting for age at SLE diagnosis, gender, ethnicity, level of education, and highest dose of prednisone for damage accrual, plus highest dose of prednisone, baseline SLEDAI, and baseline SDI for mortality. RESULTS: Of the 1437 included in these analyses, the median time to diagnosis was 6.0 months (Q1-Q3 2.4-16.2); in 721 (50.2%) the time to diagnosis was longer than 6 months. Patients whose diagnosis took longer than 6 months were more frequently female, older at diagnosis, of Mestizo ethnicity, not having medical insurance, and having "non-classic" SLE symptoms. Longer time to diagnosis had no impact on either damage accrual (HR 1.09, 95% CI 0.93-1.28, p = 0.300) or mortality (HR 1.37, 95% CI 0.88-2.12, p = 0.200). CONCLUSIONS: In this inception cohort, a maximum time of 24 months with a median of 6 months to SLE diagnosis had no apparent negative impact on disease outcomes (damage accrual and mortality).


Asunto(s)
Lupus Eritematoso Sistémico , Femenino , Humanos , Progresión de la Enfermedad , Hispánicos o Latinos , América Latina/epidemiología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , Prednisona/uso terapéutico , Índice de Severidad de la Enfermedad , Masculino
3.
Lupus ; 32(5): 658-667, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36916674

RESUMEN

OBJECTIVE: To determine the predictors of the occurrence of severe autoimmune hemolytic anemia (AIHA) and its impact on damage accrual and mortality in SLE patients. METHODS: Factors associated with time to severe AIHA (hemoglobin level ≤7 g/dL) occurring from the onset of SLE symptoms were examined by Cox proportional hazards regressions. The association of severe AIHA with mortality was examined by logistic regression analyses while its impact on damage was by negative binomial regression. RESULTS: Of 1,349 patients, 49 (3.6%) developed severe AIHA over a mean (SD) follow-up time of 5.4 (3.8) years. The median time from the first clinical manifestation to severe AIHA was 111 days (IQR 43-450). By multivariable analysis, male sex (HR 2.26, 95% CI 1.02-4.75, p = 0.044), and higher disease activity at diagnosis (HR 1.04, 95% CI 1.01-1.08, p = 0.025) were associated with a shorter time to severe AIHA occurrence. Of the SLEDAI descriptors, only hematologic (leukopenia and/or thrombocytopenia) showed a certain trend toward significance in the multivariable analysis (HR 2.36, 95% CI 0.91-6.13, p = 0.0772). Severe AIHA contributed neither to damage nor to mortality. CONCLUSIONS: Severe AIHA occurs during the early course of SLE. Male sex and higher disease activity at diagnosis emerged as independent predictors of a shorter time to severe AIHA occurrence. Although not statistically significant, hematological abnormalities at SLE diagnosis could predict the occurrence of severe AIHA in a shorter time. Damage and mortality did not seem to be impacted by the occurrence of severe AIHA.


Asunto(s)
Anemia Hemolítica Autoinmune , Leucopenia , Lupus Eritematoso Sistémico , Trombocitopenia , Humanos , Masculino , Lupus Eritematoso Sistémico/complicaciones , América Latina , Hispánicos o Latinos , Anemia Hemolítica Autoinmune/complicaciones , Trombocitopenia/complicaciones
4.
Lupus ; 30(9): 1481-1491, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34082589

RESUMEN

INTRODUCTION: Factors related to presentation of neuropsychiatric (NP) SLE manifestations, early in the course of the disease, and during follow up have not been clearly established. PURPOSE: To identify disease and non-disease related factors associated with NP manifestations in early SLE. METHODS: We included 1193 patients from the GLADEL inception cohort free of NP involvement at cohort entry. We evaluated the association of demographic, clinical and laboratory data with NP involvement during follow-up. STATISTICAL METHODS: Independent factors associated with NP involvement were identified using a multivariable Cox regression model. RESULTS: Factors independently associated with NP manifestations were: mestizo ethnicity (HR 1.701, 95% CI 1.282-2.258, p = 0.0002), myalgias/myositis (HR 1.832, 95% CI 1.335-2.515, p = 0.0002), pneumonitis (HR 2.476, 95% CI 1.085-5.648, p = 0.0312), shrinking lung (HR 2.428, 95% CI 1.074-5.493, p = 0.0331) and hemolytic anemia (HR 1.629, 95% CI 1.130-2.347, p = 0.0089). Longer disease duration at cohort entry (13 to 24 months) was associated with a lower risk of developing NP manifestations (HR 0.642, 95% CI 0.441-0.934, p = 0.0206). CONCLUSIONS: Patients with myalgias/myositis, pneumonitis, shrinking lung and hemolytic anemia are at higher risk of NP involvement, whereas longer disease duration at cohort entry is associated with a lower risk of developing NP involvement.


Asunto(s)
Vasculitis por Lupus del Sistema Nervioso Central/epidemiología , Anemia Hemolítica/epidemiología , Anemia Hemolítica/etiología , Femenino , Humanos , América Latina/epidemiología , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/etiología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , Vasculitis por Lupus del Sistema Nervioso Central/etiología , Masculino , Enfermedades Musculares/epidemiología , Enfermedades Musculares/etiología , Prevalencia , Factores de Tiempo
5.
RMD Open ; 6(3)2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33310863

RESUMEN

AIM: A decrease in proteinuria has been considered protective from renal damage in lupus nephritis (LN), but a cut-off point has yet to be established. The aim of this study was to identify the predictors of renal damage in patients with LN and to determine the best cut-off point for a decrease in proteinuria. METHODS: We included patients with LN defined clinically or histologically. Possible predictors of renal damage at the time of LN diagnosis were examined: proteinuria, low complement, anti-double-stranded DNA antibodies, red cell casts, creatinine level, hypertension, renal activity (assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)), prednisone dose, immunosuppressive drugs and antimalarial use. Sociodemographic variables were included at baseline. Proteinuria was assessed at baseline and at 12 months, to determine if early response (proteinuria <0.8 g/day within 12 months since LN diagnosis) is protective of renal damage occurrence. Renal damage was defined as an increase of one or more points in the renal domain of The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI). Cox regression models using a backward selection method were performed. RESULTS: Five hundred and two patients with systemic lupus erythematosus patients were included; 120 patients (23.9%) accrued renal damage during their follow-up. Early response to treatment (HR=0.58), antimalarial use (HR=0.54) and a high SES (HR=0.25) were protective of renal damage occurrence, whereas male gender (HR=1.83), hypertension (HR=1.86) and the renal component of the SLEDAI (HR=2.02) were risk factors for its occurrence. CONCLUSIONS: Early response, antimalarial use and high SES were protective of renal damage, while male gender, hypertension and higher renal activity were risk factors for its occurrence in patients with LN.


Asunto(s)
Lupus Eritematoso Sistémico , Nefritis Lúpica , Estudios de Cohortes , Humanos , América Latina/epidemiología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/epidemiología , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/epidemiología , Masculino , Prednisona/uso terapéutico
6.
BMC Biol ; 18(1): 164, 2020 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-33158444

RESUMEN

BACKGROUND: Cognitive dysfunction (CD) is common among patients with the autoimmune disease systemic lupus erythematosus (SLE). Anti-ribosomal P autoantibodies associate with this dysfunction and have neuropathogenic effects that are mediated by cross-reacting with neuronal surface P antigen (NSPA) protein. Elucidating the function of NSPA can then reveal CD pathogenic mechanisms and treatment opportunities. In the brain, NSPA somehow contributes to glutamatergic NMDA receptor (NMDAR) activity in synaptic plasticity and memory. Here we analyze the consequences of NSPA absence in KO mice considering its structural features shared with E3 ubiquitin ligases and the crucial role of ubiquitination in synaptic plasticity. RESULTS: Electrophysiological studies revealed a decreased long-term potentiation in CA3-CA1 and medial perforant pathway-dentate gyrus (MPP-DG) hippocampal circuits, reflecting glutamatergic synaptic plasticity impairment in NSPA-KO mice. The hippocampal dentate gyrus of these mice showed a lower number of Arc-positive cells indicative of decreased synaptic activity and also showed proliferation defects of neural progenitors underlying less adult neurogenesis. All this translates into poor spatial and recognition memory when NSPA is absent. A cell-based assay demonstrated ubiquitination of NSPA as a property of RBR-type E3 ligases, while biochemical analysis of synaptic regions disclosed the tyrosine phosphatase PTPMEG as a potential substrate. Mice lacking NSPA have increased levels of PTPMEG due to its reduced ubiquitination and proteasomal degradation, which correlated with lower levels of GluN2A and GluN2B NMDAR subunits only at postsynaptic densities (PSDs), indicating selective trafficking of these proteins out of PSDs. As both GluN2A and GluN2B interact with PTPMEG, tyrosine (Tyr) dephosphorylation likely drives their endocytic removal from the PSD. Actually, immunoblot analysis showed reduced phosphorylation of the GluN2B endocytic signal Tyr1472 in NSPA-KO mice. CONCLUSIONS: NSPA contributes to hippocampal plasticity and memory processes ensuring appropriate levels of adult neurogenesis and PSD-located NMDAR. PTPMEG qualifies as NSPA ubiquitination substrate that regulates Tyr phosphorylation-dependent NMDAR stability at PSDs. The NSPA/PTPMEG pathway emerges as a new regulator of glutamatergic transmission and plasticity and may provide mechanistic clues and therapeutic opportunities for anti-P-mediated pathogenicity in SLE, a still unmet need.


Asunto(s)
Antígenos de Superficie/genética , Proteínas del Tejido Nervioso/genética , Neuronas/fisiología , Proteína Tirosina Fosfatasa no Receptora Tipo 4/genética , Receptores de N-Metil-D-Aspartato/genética , Animales , Antígenos de Superficie/metabolismo , Masculino , Ratones , Proteínas del Tejido Nervioso/metabolismo , Plasticidad Neuronal , Proteína Tirosina Fosfatasa no Receptora Tipo 4/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Ubiquitinación
8.
Lupus ; 29(9): 1140-1145, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32605527

RESUMEN

OBJECTIVES: This study aimed to compare the clinical features, damage accrual, and survival of patients with familial and sporadic systemic lupus erythematosus (SLE). METHODS: A multi-ethnic, multinational Latin American SLE cohort was studied. Familial lupus was defined as patients with a first-degree SLE relative; these relatives were interviewed in person or by telephone. Clinical variables, disease activity, damage, and mortality were compared. Odds ratios (OR) and 95% confidence intervals (CI) were estimated. Hazard ratios (HR) were calculated using Cox proportional hazard adjusted for potential confounders for time to damage and mortality. RESULTS: A total of 66 (5.6%) patients had familial lupus, and 1110 (94.4%) had sporadic lupus. Both groups were predominantly female, of comparable age, and of similar ethnic distribution. Discoid lupus (OR = 1.97; 95% CI 1.08-3.60) and neurologic disorder (OR = 1.65; 95% CI 1.00-2.73) were significantly associated with familial SLE; pericarditis was negatively associated (OR = 0.35; 95% CI 0.14-0.87). The SLE Disease Activity Index and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) were similar in both groups, although the neuropsychiatric (45.4% vs. 33.5%; p = 0.04) and musculoskeletal (6.1% vs. 1.9%; p = 0.02) domains of the SDI were more frequent in familial lupus. They were not retained in the Cox models (by domains). Familial lupus was not significantly associated with damage accrual (HR = 0.69; 95% CI 0.30-1.55) or mortality (HR = 1.23; 95% CI 0.26-4.81). CONCLUSION: Familial SLE is not characterized by a more severe form of disease than sporadic lupus. We also observed that familial SLE has a higher frequency of discoid lupus and neurologic manifestations and a lower frequency of pericarditis.


Asunto(s)
Etnicidad , Lupus Eritematoso Sistémico/mortalidad , Adolescente , Adulto , Factores de Edad , Niño , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , América Latina/epidemiología , Lupus Eritematoso Discoide/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pericarditis/epidemiología , Modelos de Riesgos Proporcionales , Índice de Severidad de la Enfermedad , Factores Sexuales , Adulto Joven
9.
RMD Open ; 6(1)2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31958284

RESUMEN

OBJECTIVE: To evaluate the performance of the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) criteria in terms of earlier patients' classification in comparison to the 1982/1997 ACR or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria. MATERIALS AND METHODS: Patients from a Latin America, multiethnic, multicentre cohort, where SLE was defined using the physicians' diagnosis, were included. To calculate the sensitivity of the 2019 EULAR/ACR criteria, the 1982/1997 ACR criteria were considered the gold standard. Additionally, comparison of the 1982/1997 ACR criteria and the 2012 SLICC criteria with the 2019 EULAR/ACR criteria was performed. RESULTS: The sensitivity of the 2019 EULAR/ACR criteria when compared with the 1982/1997 ACR criteria as the gold standard was 91.3%. This new set of criteria allowed an earlier SLE patient classification in 7.4% (mean 0.67 years) and 0.6% (mean 1.47 years) than the 1982/1997 ACR and the 2012 SLICC criteria, respectively. Patients accruing the 2019 EULAR/ACR earlier than the 1982/1997 ACR criteria were more likely to have high anti-dsDNA titres; those accruing them later were less likely to have mucocutaneous and joint manifestations; this was not observed when comparing them with the 2012 SLICC criteria. CONCLUSIONS: The 2019 EULAR/ACR criteria classified earlier only a small proportion of Latin America patients than with the two other criteria sets in real-life clinical practice scenarios. Further studies in different patient populations are needed before these new criteria are adopted worldwide.


Asunto(s)
Lupus Eritematoso Sistémico/clasificación , Lupus Eritematoso Sistémico/diagnóstico , Reumatología/métodos , Sociedades Médicas , Adolescente , Adulto , Europa (Continente) , Femenino , Humanos , América Latina , Masculino , Reumatología/normas , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Estados Unidos , Adulto Joven
10.
J Rheumatol ; 47(7): 951-958, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-31474598

RESUMEN

OBJECTIVE: Genetic and environmental backgrounds influence the development of rheumatoid arthritis (RA). In Latin America, epidemiologic data are scarce. We aimed to determine the prevalence of RA in Chile in a population-based study. METHODS: The National Health Survey was a cross-sectional household survey with a stratified multistage probability sample of 6233 participants performed between August 2016 and March 2017. A screening instrument for RA was applied to a random sample of 3847 subjects > 30 years old. Positive screening was defined by at least 1 of the following: 2 swollen joints for at least 4 consecutive weeks (past/present), and/or a diagnosis of arthritis in the past. Individuals with positive screening had rheumatoid factor, anticitrullinated protein antibodies, and C-reactive protein measured, as well as clinical examination performed by a rheumatologist. Self-report of doctor-diagnosed RA was also performed. RESULTS: The screening questionnaire was applied to 2998 subjects. A positive screening was found for 783 (22.1%). Among subjects with positive screening, 493 (66%) had a clinical evaluation performed by a rheumatologist. Using the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria, prevalence was 0.6% (95% CI 0.3-1.2). Prevalence was higher in women, and 3.3% of subjects self-reported having RA. CONCLUSION: According to this national population-based study, RA prevalence in Chile is 0.6% (0.3-1.2), a value similar to what has been found in developed countries and slightly lower than some Latin American countries. Self-reporting leads to overestimating RA.


Asunto(s)
Artritis Reumatoide , Adulto , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/epidemiología , Chile/epidemiología , Estudios Transversales , Femenino , Encuestas Epidemiológicas , Humanos , Prevalencia
12.
Clin Rheumatol ; 38(11): 3129-3137, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31367942

RESUMEN

OBJECTIVE: Central nervous system disease occurs in over 20% of patients with systemic lupus erythematosus (SLE) resulting in major morbidity and damage. Cognitive dysfunction is common in SLE, but the cause remains uncertain and treatment options are limited. This study explores the influence of clinical, neuropsychological factors and anti-neuronal antibodies on lupus damage accrual. METHOD: A prospective cohort with 99 SLE patients recruited between 2008 and 2013 and followed up in 2016 was established. Baseline evaluations were depression (MINI-Plus), cognitive function evaluating attention, visuospatial memory and executive functions, and anti-neuronal antibodies. Activity index (SLEDAI-2K) and SLICC/ACR Damage Index (SDI) were assessed at baseline and last follow-up. RESULTS: At baseline, median (interquartile range) age was 36.0 years (27.0-45.0), disease duration 3.7 years (0.4-12.4), SLEDAI-2K 6.0 (3.0-12.0), and SDI score 1.0 (0-1.0). Major depression was present in 23%, cognitive deficit in 18%, and received immunomodulators in 36%. Anti-dsDNA/N-methyl-D-aspartate receptor antibodies were present in 19%, anti-ribosomal P in 12%, and anti-neuronal surface P antigen (NSPA) in 5%. After a median follow-up of 55 months (interquartile range 39-78), 11% had damage accrual. In a multivariate analysis, baseline SDI, SLEDAI-2K, and immunomodulators use were associated with final damage, whereas SLEDAI-2K and immunomodulator use were also associated with accrual damage. Models including anti-NSPA showed impact on final and accrual damage. Cognitive deficit, depression, and other autoantibodies were not predictors. CONCLUSIONS: Disease activity and immunomodulator use associate with lupus damage. Of the anti-neuronal antibodies examined, anti-NSPA emerged as a potential poor prognostic factor, probably related to severe SLE onset requiring elevated corticosteroid doses. Key Points • Anti-NSPA may be a worse prognostic factor in SLE. • Other neuropsychological factors do not influence damage.


Asunto(s)
Lupus Eritematoso Sistémico/psicología , Neuronas/inmunología , Adulto , Disfunción Cognitiva/etiología , Depresión/etiología , Femenino , Humanos , Factores Inmunológicos/efectos adversos , Estudios Longitudinales , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Persona de Mediana Edad
13.
Mol Neurobiol ; 56(11): 7774-7788, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31119556

RESUMEN

Galectin-8 (Gal-8) is a glycan-binding protein that modulates a variety of cellular processes interacting with cell surface glycoproteins. Neutralizing anti-Gal-8 antibodies that block Gal-8 functions have been described in autoimmune and inflammatory disorders, likely playing pathogenic roles. In the brain, Gal-8 is highly expressed in the choroid plexus and accordingly has been detected in human cerebrospinal fluid. It protects against central nervous system autoimmune damage through its immune-suppressive potential. Whether Gal-8 plays a direct role upon neurons remains unknown. Here, we show that Gal-8 protects hippocampal neurons in primary culture against damaging conditions such as nutrient deprivation, glutamate-induced excitotoxicity, hydrogen peroxide (H2O2)-induced oxidative stress, and ß-amyloid oligomers (Aßo). This protective action is manifested even after 2 h of exposure to the harmful condition. Pull-down assays demonstrate binding of Gal-8 to selected ß1-integrins, including α3 and α5ß1. Furthermore, Gal-8 activates ß1-integrins, ERK1/2, and PI3K/AKT signaling pathways that mediate neuroprotection. Hippocampal neurons in primary culture produce and secrete Gal-8, and their survival decreases upon incubation with human function-blocking Gal-8 autoantibodies obtained from lupus patients. Despite the low levels of Gal-8 expression detected by real-time PCR in hippocampus, compared with other brain regions, the complete lack of Gal-8 in Gal-8 KO mice determines higher levels of apoptosis upon H2O2 stereotaxic injection in this region. Therefore, endogenous Gal-8 likely contributes to generate a neuroprotective environment in the brain, which might be eventually counteracted by human function-blocking autoantibodies.


Asunto(s)
Anticuerpos Neutralizantes/farmacología , Autoanticuerpos/farmacología , Encéfalo/metabolismo , Galectinas/metabolismo , Neuroprotección , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Hipocampo/patología , Humanos , Peróxido de Hidrógeno/metabolismo , Integrina beta1/metabolismo , Neuronas/efectos de los fármacos , Neuronas/patología , Neuroprotección/efectos de los fármacos , Unión Proteica/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos
14.
J Clin Rheumatol ; 25(1): 54-58, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29596208

RESUMEN

BACKGROUND: By 2015, the World Health Organization reported that 1% of the world population suffered from rheumatoid arthritis (RA) and in Latin America (LA) between 0.5% and 1%. Previously, in May 2014, a consensus meeting was held in Barranquilla, Colombia, where the Project for Implementation and Accreditation of Centers of Excellence (CoE) in RA in LA was established, which then became an official special group of the Pan American League of Associations for Rheumatology (PANLAR). OBJECTIVE: The aim of this study was to define the methodological approach for the accreditation process of CoE in RA in LA. METHODS: A meeting was held in April 2015 with participation of the members of the REAL-PANLAR Steering Committee, and representatives of several LA countries, with the support of 2 experts in accreditation processes and models in Colombia. Then, in November 2015 in San Francisco and in November 2016 in Washington, the REAL-PANLAR Steering Committee met to discuss some final aspects of the project. RESULTS: The following steps for accreditation were defined: application for accreditation, issuance of the concept of assessment of the entity, accreditation decision, and monitoring accreditation. CONCLUSIONS: This is the second REAL-PANLAR consensus paper with the purpose to define the parameters for the accreditation process for future CoE in RA in LA.


Asunto(s)
Acreditación , Artritis Reumatoide/terapia , Atención a la Salud , Reumatología , Consenso , Humanos , América Latina , Sociedades Médicas
15.
Rev. argent. reumatol ; 29(3): 6-10, set. 2018. tab
Artículo en Español | LILACS | ID: biblio-977290

RESUMEN

Objetivos: Estimar el efecto de los antimaláricos (AM) sobre los diferentes dominios del índice de daño SLICC (SDI). Métodos: Se estudiaron pacientes con diagnóstico clínico reciente (≤2 años) de lupus eritematoso sistémico (LES) de la cohorte GLADEL. Variable de estudio: aumento en los dominios del SDI desde el ingreso a la cohorte. Variables independientes: características sociodemográficas, clínicas, laboratorio y tratamientos. El efecto de los AM, como variable dependiente del tiempo, sobre los dominios más frecuentes del SDI (ajustado por factores de confusión) fue examinado con un modelo de regresión de Cox multivariado. Resultados: De 1466 pacientes estudiados, 1049 (72%) recibieron AM con un tiempo medio de exposición de 30 meses (Q1-Q3: 11-57) y 665 pacientes (45%) presentaron daño durante un seguimiento medio de 24 meses (Q1-Q3: 8-55); 301 eventos fueron cutáneos, 208 renales, 149 neuropsiquiátricos, 98 musculoesqueléticos, 88 cardiovasculares y 230 otros. Después de ajustar por factores de confusión, el uso de AM se asoció a un menor riesgo de daño renal (HR 0,652; IC 95%: 0,472-0,901) y en el límite de la significancia estadística (HR 0,701, IC 95%: 0,481-1,024) para el dominio neuropsiquiátrico. Conclusión: En GLADEL, el uso de AM se asoció independientemente a un menor riesgo de daño acumulado renal.


Objective: To assess the effects of antimalarials (AM) over the items of the SLICC Damage Index (SDI). Methods: Patients with recent (≤2 years) diagnosis of systemic lupus erythematosus (SLE) from the GLADEL cohort were studied. End-point: increase in items SDI since cohort entry. Independent variables (socio-demographic, clinical, laboratory and treatment) were included. The effect of AM as a time dependent variable on most frequent SDI items (adjusting for potential confounders) was examined with a multivariable Cox regression model. Results: Of the 1466 patients included in this analysis, 1049 (72%) received AM with a median exposure time of 30 months (Q1-Q3: 11-57). Damage occurred in 665 (45%) patients during a median follow-up time of 24 months (Q1-Q3: 8-55). There were 301 integument, 208 renal, 149 neuropsychiatric, 98 musculoskeletal, 88 cardiovascular and 230 others less frequently represented damages. After adjusting for potential confounders at any time during follow-up, a lower risk of renal damage (HR 0.652; 95% CI: 0.472-0.901) and borderline for neuropsychiatric damage (HR 0.701, 95% CI: 0.481-1.024) was found. Conclusion: In the GLADEL cohort, after adjustment for possible confounding factors, AM were independently associated with a reduced risk of renal damage accrual.


Asunto(s)
Lupus Eritematoso Sistémico , Antimaláricos
16.
Ann Rheum Dis ; 77(11): 1549-1557, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30045853

RESUMEN

Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an 'overarching' treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings.


Asunto(s)
Síndrome Antifosfolípido/tratamiento farmacológico , Enfermedades Hematológicas/tratamiento farmacológico , Enfermedades Renales/tratamiento farmacológico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Síndrome Antifosfolípido/etiología , Cardiopatías/tratamiento farmacológico , Cardiopatías/etiología , Enfermedades Hematológicas/etiología , Humanos , Enfermedades Renales/etiología , América Latina , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/etiología , Lupus Eritematoso Sistémico/complicaciones , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/etiología , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/etiología , Enfermedades Musculoesqueléticas/tratamiento farmacológico , Enfermedades Musculoesqueléticas/etiología , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/etiología , Nivel de Atención
17.
Rev Med Chil ; 146(2): 241-248, 2018 Feb.
Artículo en Español | MEDLINE | ID: mdl-29999161

RESUMEN

Renal involvement is a frequent complication in antineutrophil cytoplasmic antibodies (ANCA)associated vasculitides, adding morbidity and mortality, such as chronic kidney disease and the need for renal replacement therapy. With the aim of reaching a consensus on relevant issues regarding the diagnosis, treatment and follow-up of patients with these diseases, the Chilean Societies of Nephrology and Rheumatology formed a working group that, based on a critical review of the available literature and their experience, raised and answered consensually a set of questions relevant to the subject. This document includes aspects related to the clinical diagnosis, the histological characteristics, the therapeutic alternatives to induce and maintain the remission of the disease, relapse surveillance strategies and complementary therapies.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Enfermedades Renales/etiología , Enfermedades Renales/terapia , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/sangre , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Chile , Humanos , Quimioterapia de Mantención , Inducción de Remisión , Sociedades Médicas
18.
Curr Opin Neurol ; 31(3): 300-305, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29461425

RESUMEN

PURPOSE OF REVIEW: Analysis of antiribosomal P protein autoantibodies (anti-P) pathogenicity in diffuse brain manifestations of neuropsychiatric lupus, emphasizing cognitive dysfunction and the recently emerged role of cross-reacting neuronal surface P antigen (NSPA) in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-Methyl-D-Aspartate receptor glutamatergic transmission. RECENT FINDINGS: Circulating anti-P antibodies associate with executive planning dysfunction and attention impairments in lupus patients and perturb glutamatergic transmission through NSPA in mice hippocampus, translating into impaired synaptic plasticity and spatial memory. Planning impairment impacts quality of life. SUMMARY: In addition to the known association with lupus psychosis, new clinical and experimental evidence reveal a pathogenic role of anti-P antibodies in cognitive dysfunction, mechanistically explained by the anti-P interaction with NSPA as a target involved in glutamatergic synaptic plasticity.


Asunto(s)
Autoanticuerpos , Encéfalo/inmunología , Lupus Eritematoso Sistémico/inmunología , Proteínas Ribosómicas/inmunología , Animales , Disfunción Cognitiva/inmunología , Humanos , Ratones
19.
Rev. méd. Chile ; 146(2): 241-248, feb. 2018.
Artículo en Español | LILACS | ID: biblio-961383

RESUMEN

Renal involvement is a frequent complication in antineutrophil cytoplasmic antibodies (ANCA)associated vasculitides, adding morbidity and mortality, such as chronic kidney disease and the need for renal replacement therapy. With the aim of reaching a consensus on relevant issues regarding the diagnosis, treatment and follow-up of patients with these diseases, the Chilean Societies of Nephrology and Rheumatology formed a working group that, based on a critical review of the available literature and their experience, raised and answered consensually a set of questions relevant to the subject. This document includes aspects related to the clinical diagnosis, the histological characteristics, the therapeutic alternatives to induce and maintain the remission of the disease, relapse surveillance strategies and complementary therapies.


Asunto(s)
Humanos , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Enfermedades Renales/etiología , Enfermedades Renales/terapia , Sociedades Médicas , Inducción de Remisión , Chile , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/sangre , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Quimioterapia de Mantención
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