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B and T cell responses were evaluated in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) after 1 or 2 weeks of methotrexate (MTX) withdrawal following each COVID-19 vaccine dose and compared with those who maintained MTX. Adult RA and PsA patients treated with MTX were recruited and randomly assigned to 3 groups: MTX-maintenance (n = 72), MTX-withdrawal for 1 week (n = 71) or MTX-withdrawal for 2 weeks (n = 73). Specific antibodies to several SARS-CoV-2 antigens and interferon (IFN)-γ and interleukin (IL)-21 responses were assessed. MTX withdrawal in patients without previous COVID-19 was associated with higher levels of anti-RBD IgG and neutralising antibodies, especially in the 2-week withdrawal group and with higher IFN-γ secretion upon stimulation with pools of SARS-CoV-2 S peptides. No increment of RA/PsA relapses was detected across groups. Our data indicate that two-week MTX interruption following COVID-19 vaccination in patients with RA or PsA improves humoral and cellular immune responses.
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ITGAM-ITGAX (rs11150612, rs11574637), VAV3 rs17019602, CARD9 rs4077515, DEFA (rs2738048, rs10086568), and HORMAD2 rs2412971 are mucosal immune defence polymorphisms, that have an impact on IgA production, described as risk loci for IgA nephropathy (IgAN). Since IgAN and Immunoglobulin-A vasculitis (IgAV) share molecular mechanisms, with the aberrant deposit of IgA1 being the main pathophysiologic feature of both entities, we assessed the potential influence of the seven abovementioned polymorphisms on IgAV pathogenesis. These seven variants were genotyped in 381 Caucasian IgAV patients and 997 matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of these seven polymorphisms when the whole cohort of IgAV patients and those with nephritis were compared to controls. Similar genotype and allele frequencies of all polymorphisms were disclosed when IgAV patients were stratified according to the age at disease onset or the presence/absence of gastrointestinal or renal manifestations. Likewise, no ITGAM-ITGAX and DEFA haplotype differences were observed when the whole cohort of IgAV patients, along with those with nephritis and controls, as well as IgAV patients, stratified according to the abovementioned clinical characteristics, were compared. Our results suggest that mucosal immune defence polymorphisms do not represent novel genetic risk factors for IgAV pathogenesis.
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Glomerulonefritis por IGA , Vasculitis por IgA , Inmunidad Mucosa , Nefritis , Humanos , Antígeno CD11c , Frecuencia de los Genes , Genotipo , Glomerulonefritis por IGA/genética , Vasculitis por IgA/genética , Polimorfismo Genético , Inmunidad Mucosa/genéticaRESUMEN
This study aimed to analyze the factors that influence anti-citrullinated protein antibody (ACPA) titers in a seropositive early arthritis (EA) population under non-protocolized treatment with disease-modifying anti-rheumatic drugs (DMARDs). A total of 130 ACPA-positive patients from the PEARL (Princesa Early Arthritis Longitudinal) study were studied along a 5-year follow-up. Sociodemographic, clinical, and therapeutic variables, along with serum samples, were collected at five visits by protocol. Anti-cyclic citrullinated peptide 2 (CCP2) ACPA titers were measured by ELISA. The effect of different variables on anti-CCP2 titers was estimated using longitudinal multivariate analysis models, nested by visit and patient. Data from 471 visits in 130 patients were analyzed. A significant decrease in anti-CCP2 titers was observed at all time-points, compared to baseline, following the decline of disease activity. In the multivariate analysis, active or ever smoking was significantly associated with the highest anti-CCP2 titers while reduction in disease activity was associated with titer decline. After adjusting for these variables, both conventional synthetic (cs) and biologic (b) DMARDs accounted for the decline in anti-CCP2 titers as independent factors. Conclusion: In patients with EA, an early and sustained reduction in ACPA titers can be detected associated with the decline in disease activity, irrespective of the treatment used.
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BACKGROUND: Plasma concentrations of lipoprotein (a) (Lp(a)), a lipoprotein with atherogenic and thrombogenic properties, have a strong genetic basis, although high concentrations of Lp(a) have also been reported in the context of inflammation, as in rheumatoid arthritis (RA). Few studies evaluate the impact of biologic therapies (BT) on Lp(a) in RA, taking into account that with these new therapies a better control of inflammation is achieved. OBJECTIVE: The aim of the study was to evaluate the plasma concentrations of Lp(a) in Spanish RA patients on BT attending rheumatology outpatient clinics. METHODS: Baseline analysis of the CARdiovascular in rheuMAtology project, a 10-year prospective study, evaluating the risk of cardiovascular events in RA and other forms of inflammatory arthritis. RA patients were classified according to treatment: no biologic, anti-tumor necrosis factor, anti-interleukin-6 receptor tocilizumab (TCZ), and other biologic (rituximab or abatacept). A model of linear multivariate regression was built in which the dependent variable was Lp(a) concentration and the explanatory variable was BT. The model was adjusted for confounding factors. RESULTS: Seven hundred and seventy-five RA patients were analyzed. Plasma concentrations of total cholesterol and triglyceride were significantly higher in TCZ-treated patients. Nevertheless, no significant difference in the atherogenic index between TCZ-treated patients and patients without BT was found. After adjusting for confounding factors, patients with BT had lower concentrations of Lp(a) than those without BT; however, only TCZ-treated patients achieved statistically significant differences (ß: -0.303, 95% confidence interval: -0.558 to -0.047; P = .02). CONCLUSIONS: RA patients treated with TCZ show lower plasma concentrations of Lp(a) compared with patients without BT.
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Artritis Reumatoide/sangre , Artritis Reumatoide/terapia , Terapia Biológica , Lipoproteína(a)/sangre , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , RiesgoRESUMEN
OBJECTIVE: Describe the demographic characteristics and disorders of patients with diagnosis of Macrophage Activation Syndrome (MAS) in the December 2008 - January 2014 period. METHODS: Medical records were reviewed from diagnosis of MAS and after discharge until January 2014. Patients were divided into 4 groups according to the primary disease: Autoimmune (AI), Hemato - oncologic (HO), Infectious (Inf) and Oncologic (Onc). The variables were analyzed among the 4 groups and between AI and HO. RESULTS: Thirteen patients [7 men, with a median of 54 years (32-63)] were studied. The etiologies were: 5 AI, 5 HO, 2 Inf. and 1 Onc. disease. Hemophagocitc cells were found in the ascitic fluid of one patient. A patient with MAS secondary to IgG4-related disease was found. CONCLUSIONS: Mortality, prognosis and disease progression may be influenced by the delay in diagnosis, treatment initiation and etiology of MAS. HO ill patients had a worse prognosis.
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Enfermedades Autoinmunes/complicaciones , Enfermedades Hematológicas/complicaciones , Infecciones/complicaciones , Síndrome de Activación Macrofágica/etiología , Neoplasias/complicaciones , Adulto , Enfermedades Autoinmunes/diagnóstico , Progresión de la Enfermedad , Femenino , Enfermedades Hematológicas/diagnóstico , Humanos , Infecciones/diagnóstico , Síndrome de Activación Macrofágica/diagnóstico , Síndrome de Activación Macrofágica/mortalidad , Síndrome de Activación Macrofágica/terapia , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico , PronósticoRESUMEN
INTRODUCTION: Hemophagocytic syndrome (HS) occurs in autoimmune diseases and belongs to the hemophagocytic lymphohistiocytosis group of diseases. This paper describes the features of 2 patients with systemic lupus erythematosus (SLE) who presented HS as the initial clinical manifestation. CLINICAL OBSERVATIONS: Both patients had prolonged fever not associated to an infectious process and did not respond to broad-spectrum antibiotics. DISCUSSION: The diagnosis of HS secondary to SLE is complicated, because it has some features in common, but HS is characterized by hyperferritinemia, hipofibrinogemia, hypertriglyceridemia and a decrease in the erythrocyte sedimentation rate, unlike SLE. HS treatment when associated to SLE is not well established, but steroids and/or immunoglobulins are effective as the initial treatment, and in refractory cases, cyclosporine or cyclophosphamide may be associated. CONCLUSIONS: HS can be the initial manifestation of SLE and should be suspected in patients with organ enlargement, cytopenias, clotting disorders, liver disorders and prolonged fever unresponsive to antibiotics. Anakinra may be a treatment option in adult HS associated to SLE.