Humoral and T Cell Response to SARS-CoV-2 Vaccination in Patients With Rheumatoid Arthritis.

OBJECTIVE: The objective of this study was to assess the SARS-CoV-2-specific humoral and T cell response after a two-dose regimen of SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA). METHODS: In this observational study, patients with RA who are ≥18 years of age and vaccinated for SARS-CoV-2 according to the Argentine National Health Ministry's vaccination strategy were included. Anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies (ELISA-COVIDAR test), neutralizing activity (cytotoxicity in VERO cells), and specific T cell response (IFN-γ ELISpot Assay) were assessed after the first and second dose. RESULTS: A total of 120 patients with RA were included. Mostly, homologous regimens were used, including Gam-COVID-Vac (27.5%), ChAdOx1 (24.2%), and BBIBP-CorV (22.5%). The most frequent combination was Gam-COVID-Vac/mRNA-1273 (21.7%). After the second dose, 81.7% presented with anti-SARS-CoV-2 antibodies, 70.0% presented with neutralizing activity, and 65.3% presented with specific T cell response. The use of BBIBP-CorV and treatment with abatacept (ABA) and rituximab (RTX) were associated with undetectable antibodies and no neutralizing activity after two doses. BBIBP-CorV was also associated with the absence of T cell response. The total incidence of adverse events was 357.1 events per 1,000 doses, significantly lower with BBIBP-CorV (166.7 events per 1,000 doses, P < 0.02). CONCLUSION: In this RA cohort vaccinated with homologous and heterologous regimens against COVID-19, 2 out of 10 patients did not develop anti-SARS-CoV-2 IgG, 70% presented with neutralizing activity, and 65% presented with specific T cell response. The use of BBIBP-CorV was associated with deficient humoral and cellular response, whereas treatment with ABA and RTX resulted in an impaired anti-SARS-CoV-2 IgG formation and neutralizing activity.

Immune Response to SARS-CoV-2 Third Vaccine in Patients With Rheumatoid Arthritis Who Had No Seroconversion After Primary 2-Dose Regimen With Inactivated or Vector-Based Vaccines.

OBJECTIVE: The aim of this study was to assess the immune response after a third dose of SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA) with undetectable antibody titers after the primary regimen of 2 doses. METHODS: Patients with RA with no seroconversion after 2 doses of SARS-CoV-2 vaccine and who received a third dose of either an mRNA or vector-based vaccine were included. Anti-SARS-CoV-2 IgG antibodies, neutralizing activity, and T cell responses were assessed after the third dose. RESULTS: A total of 21 nonresponder patients were included. At the time of vaccination, 29% were receiving glucocorticoids and 85% biologic disease-modifying antirheumatic drugs (including 6 taking abatacept [ABA] and 4 taking rituximab [RTX]). The majority (95%) received the BNT162b2 vaccine and only one of them received the ChAdOx1 nCoV-19 vaccine. After the third dose, 91% of the patients presented detectable anti-SARS-CoV-2 IgG and 76% showed neutralizing activity. Compared to other treatments, ABA and RTX were associated with the absence of neutralizing activity in 4 out of 5 (80%) patients and lower titers of neutralizing antibodies (median 3, IQR 0-20 vs 8, IQR 4-128; P = 0.20). Specific T cell response was detected in 41% of all patients after the second dose, increasing to 71% after the third dose. The use of ABA was associated with a lower frequency of T cell response (33% vs 87%, P = 0.03). CONCLUSION: In this RA cohort, 91% of patients who failed to seroconvert after 2 doses of SARS-CoV-2 vaccine presented detectable anti-SARS-CoV-2 IgG after a third dose. The use of ABA was associated with a lower frequency of specific T cell response.

Impacto de la presencia de depresión y ansiedad en pacientes con artritis psoriásica / Impact of depression and anxiety in patients with psoriatic arthritis

Introducción: un tercio de los pacientes con artritis psoriásica (APs) sufre ansiedad y/o depresión, lo que podría impactar negativamente en la actividad de la enfermedad. Los objetivos de este estudio fueron: evaluar la prevalencia de depresión y ansiedad en pacientes con APs, estudiar su asociación con diferentes factores sociodemográficos y clínicos, y determinar el efecto sobre los diferentes componentes de los índices compuestos de la actividad de la APs. Materiales y métodos: se incluyeron pacientes con APs que cumplían criterios de la Classification criteria of psoriatic arthritis (CASPAR). La depresión se definió según el Patient Health Questionnaire-9 (PHQ-9) y la ansiedad según el cuestionario General Anxiety Disorder-7 (GAD-7). Se realizó regresión logística múltiple para identificar variables asociadas a ansiedad y depresión. Resultados: se incluyeron 100 pacientes con APs, de los cuales el 26% y el 59% presentaron depresión mayor y ansiedad respectivamente. Los pacientes con depresión mayor tuvieron mayor actividad de la enfermedad, dolor, fatiga, ansiedad, y menor educación formal y peor calidad de vida. Aquellos con ansiedad manifestaron mayor actividad de la enfermedad, dolor y fatiga, y peor calidad de vida y capacidad funcional. La alta actividad de la enfermedad y la menor educación formal se asociaron independientemente con depresión mayor. Conclusiones: la presencia de depresión mayor y ansiedad se asoció con mayor actividad de la enfermedad en pacientes con APs.

Introduction: nearly one-third of psoriatic arthritis (PsA) patients suffer from anxiety and/or depression. The objectives of this study were to estimate the prevalence of depression and anxiety in patients with PsA, establish the relationship with different socio-demographic and clinical factors, and determine the effect of depression and anxiety on various components of disease activity scores. Materials and methods: patients with PsA who met the Classification criteria of psoriatic arthritis (CASPAR) criteria were included. Depression was defined according to the Patient Health Questionnaire-9 (PHQ-9) and anxiety according to the General Anxiety Disorder-7 (GAD-7) questionnaire. Multiple logistic regression was performed to identify variables associated with anxiety and depression. Results: 100 patients were included. The prevalence of major depression and anxiety was 26% and 59%, respectively. Patients with major depression had higher disease activity, pain, fatigue and anxiety, less formal education and worse quality of life. In comparison those patients with anxiety showed higher disease activity, pain and fatigue and worse quality of life and functional capacity. High disease activity and low formal education were independently associated with the existence of major depression. Conclusions: patients with PsA who suffer from major depression and anxiety show higher disease activity levels.

Adherencia al tratamiento con tofacitinib en pacientes con artritis reumatoide en la práctica clínica diaria / Adherence to Treatment with Tofacitinib in Patients with Rheumatoid Arthritis in Daily Clinical Practice

Objetivos: Evaluar la adherencia al tratamiento con tofacitinib en pacientes con artritis reumatoide (AR) mediante las dos versiones del autocuestionario Compliance Questionnaire Rheumatology, CQR19 y CQR5, determinar las variables asociadas a la adherencia a tofacitinib y comparar el rendimiento de ambos cuestionarios. Material y métodos: Estudio de corte transversal. Se incluyeron pacientes ≥18años de edad con AR (ACR/EULAR 2010) en tratamiento con tofacitinib. Se consignaron datos sociodemográficos, características clínicas de la enfermedad, tratamientos y datos sobre la evaluación de los pacientes. Todos los pacientes completaron los autocuestionarios CQR19 y CQR5. Análisis estadístico: Estadística descriptiva. T-test o Mann Whitney para variables continuas y test de chi cuadrado o test exacto de Fisher para las categóricas. Índice de concordancia kappa. Regresión logística múltiple. Resultados: Se incluyeron 52 pacientes, 82,7% mujeres, con una edad mediana (m) de 57,7años, tiempo de evolución de la enfermedad m 16años. El 63,5% presentaban comorbilidades. El 86,5% de los pacientes estaban tratados con tofacitinib (5mg dos veces/día) y el 48% recibía tofacitinib en monoterapia. El tiempo m de tratamiento con tofacitinib fue de 13meses. El 42,3% suspendieron el tratamiento y un solo paciente suspendió definitivamente por falta de provisión. La m de CQR19 fue del 89,5%, y el 84,6% de los pacientes presentaron una adherencia ≥80%. Las variables significativamente asociadas con adherencia ≥80% fueron la presencia de comorbilidades (p=0,014) y mayor edad (p=0,033). Considerando el CQR5, un porcentaje similar de pacientes (82,7%) fueron adherentes al tratamiento, aunque la concordancia con CQR19 fue baja (??: 0,227). En el análisis multivariado, mayor edad fue la única variable independientemente asociada a buena adherencia al tratamiento (p=0,037).(AU)

Objectives: To evaluate the adherence to treatment with tofacitinib in patients with rheumatoid arthritis (RA) using two versions of the self-questionnaire Compliance Questionnaire Rheumatology, CQR19 and CQR5, to determine the variables associated with adherence to tofacitinib and to compare the performance of both questionnaires. Material and methods: A cross-sectional study was carried out. We included patients ≥18years old, with RA (ACR/EULAR criteria 2010) under treatment with tofacitinib. Sociodemographic data, clinical characteristics, treatment and data on patient evaluation. All the patients completed self-questionnaires CQR19 and CQR5. Statistical analysis: Descriptive statistics. T-test or Mann Whitney to compare the continuous variables, chi2 test or Fisher's exact test for the categorical ones. Kappa concordance index. Multiple logistic regression. Results: We included 52 patients, 82.7% women, with a median (m) age of 57.7years, disease duration m 16years, 63.5% had comorbidities. Of the patients, 86.5% were treated with tofacitinib (5mg BID) and 48% received tofacitinib as monotherapy. The median time of tofacitinib treatment was 13months, 42.3% suspended treatment, and only one patient permanently stopped treatment due to lack of provision. Median CQR19 was 89.5%, and 84.6% had an adherence ≥80%. The variables significantly associated with adherence ≥80% were the presence of comorbidities (P=.014) and older age (P=.033). Considering the CQR5, a similar percentage of patients (82.7%) were adherents to treatment, however, the concordance with CQR19 was low. In the multivariate analysis, older age was the only variable independently associated with good adherence to treatment. Conclusions: Treatment adherence to tofacitinib was very good for both presentations. Older age was associated with higher adherence. The agreement between the questionnaires CQR19 and CQR5 was low.(AU)

Adherence to treatment with tofacitinib in patients with rheumatoid arthritis in daily clinical practice.

OBJECTIVES: To evaluate the adherence to treatment with Tofacitinib in patients with Rheumatoid Arthritis (RA) using two versions of the self-questionnaire Compliance Questionnaire Rheumatology, CQR19 and CQR5, to determine the variables associated with adherence to Tofacitinib and to compare the performance of both questionnaires. MATERIAL AND METHODS: A cross-sectional study was carried out. We included patients ≥18 years old, with RA (ACR/EULAR criteria 2010) under treatment with Tofacitinib. Sociodemographic data, clinical characteristics, treatment and data on patient evaluation. All the patients completed self-questionnaires CQR19 and CQR5. STATISTICAL ANALYSIS: Descriptive statistics. t-Test or Mann Whitney to compare the continuous variables, Chi2 test or Fisher's exact test for the categorical ones. Kappa concordance index. Multiple logistic regression. RESULTS: We included 52 patients, 82.7% women, with a median (m) age of 57.7 years, disease duration m 16 years, 63.5% had comorbidities. Of the patients, 86.5% were treated with Tofacitinib (5 mg BID) and 48% received Tofacitinib as monotherapy. The median time of Tofacitinib treatment was 13 months, 42.3% suspended treatment, and only one patient permanently stopped treatment due to lack of provision. Median CQR19 was 89.5% and 84.6% had an adherence ≥ 80%. The variables significantly associated with adherence ≥ 80% were the presence of comorbidities (p = .014) and older age (p = .033). Considering the CQR5, a similar percentage of patients (82.7%) were adherents to treatment, however, the concordance with CQR19 was low. In the multivariate analysis, older age was the only variable independently associated with good adherence to treatment. CONCLUSIONS: Treatment adherence to Tofacitinib was very good for both presentations. Older age was associated with higher adherence. The agreement between the questionnaires CQR19 and CQR5 was low.

Respuesta immune humoral asociada a las vacunas contra SARS-CoV-2 en pacientes con artritis reumatoidea: datos del registro SAR-CoVAC / Humoral immune response associated to the vaccines against SARS-CoV-2 in patients with rheumatic arthritis: data from the SAR-CoVAC registry

Introducción: la artritis reumatoidea (AR) y los tratamientos indicados para su manejo pueden afectar la respuesta a la vacuna para SARS-CoV-2. Sin embargo, aún no se cuenta con datos locales. Objetivos: evaluar la respuesta humoral de la vacuna para SARS-CoV-2 y su seguridad en esta población. Materiales y métodos: estudio observacional. Se incluyeron pacientes ≥18 años, con AR ACR/EULAR 2010 que recibieron la vacunación para SARS-CoV-2. Detección de IgG anti-proteína S (kit COVIDAR). Resultados: se incluyeron 120 pacientes con AR. El 24,4% recibió tratamiento con glucocorticoides, 50,9% drogas biológicas y 13,3% inhibidores de JAK (janus kinases). El 6% había tenido infección por SARS-CoV-2 previamente. La vacuna más utilizada en la primera dosis fue Sputnik V (52,9%). El 25% recibió esquemas heterólogos. Luego de la primera dosis, el 59% presentó una prueba no reactiva o indeterminada, y un 18% luego de la segunda dosis. La aplicación de esquemas homólogos de vacuna Sinopharm (63,6% vs 13,3%, p<0,0001), y el uso de abatacept (27,3% vs 5,1%, p=0,005) y rituximab (18,2% vs 0%, p=0,001) al momento de la vacunación se asociaron a un resultado no reactivo o indeterminado. Conclusiones: similar a lo reportado en otras poblaciones internacionales, en esta cohorte, dos de cada 10 pacientes no desarrollaron anticuerpos. Una menor respuesta se asoció con la vacuna Sinopharm y al tratamiento con abatacept y rituximab.

Introduction: rheumatoid arthritis (RA) and its treatments can affect the response to the SARS-CoV-2 vaccine. However, we still do not have local data. Objectives: to evaluate the humoral response of the SARS-CoV-2 vaccine and its safety in this population. Materials and methods: observational study. Patients ≥18 years of age, with RA ACR/EULAR 2010 who had received vaccination for SARS-CoV-2 were included. Detection of anti-protein S IgG (COVIDAR Kit). Results: a total of 120 patients with RA were included. A quarter was receiving glucocorticoids, 50.9% biological drugs and 13.3% JAK inhibitors (janus kinases). Only 6% had a history SARS-CoV-2 infection. The most used vaccine was Sputnik V (52.9%) and 25% received mixed regimenes. After the first dose, 59% had a non-reactive or indeterminate test, and after the second, 18% were still having this result. The application of homologous Sinopharm vaccine regimen (63.6% vs 13.3%, p<0.0001) and the use of abatacept (27.3% vs 5.1%, p=0.005) and rituximab (18.2% vs 0%, p=0.001) at vaccination was associated with a non-reactive or indeterminate result. Conclusions: similar to other international populations, in this cohort, two out of 10 patients did not develop antibodies. A lower response was associated with the Sinopharm vaccine and treatment with abatacept and rituximab.

Effect of Tocilizumab on LDL and HDL Characteristics in Patients with Rheumatoid Arthritis. An Observational Study.

BACKGROUND: In patients with rheumatoid arthritis (RA), qualitative alterations of low and high-density lipoproteins (LDL and HDL, respectively) might partially explain their increased cardiovascular risk. Tocilizumab has been associated with an increase in lipids, including triglyceride (TG) and cholesterol levels. The aim of this study is to evaluate the effect of tocilizumab on certain LDL and HDL characteristics (oxidized LDL levels, HDL-associated enzymes, chemical composition of both total HDL and HDL3c subpopulation, and their capacity to promote cellular cholesterol efflux) at baseline and 3 months after the start of treatment in patients with RA. METHODS: Twenty-eight RA patients (ACR/EULAR 2010 criteria) with indication of treatment with tocilizumab were included in the present study. Clinical assessment [Health assessment questionnaire (HAQ)], disease activity score 28 (DAS28), high-sensitivity C reactive protein (hsCRP) concentration, lipid profile, and lipoprotein (a) [Lp(a)] levels were evaluated in all patients at baseline and after 3 months of treatment with tocilizumab. Lipoprotein characteristics were evaluated through the levels of oxidized LDL (OxLDL), the activity of paraoxonase (PON) 1, the composition of total HDL and small, dense HDL3c subpopulation, and their ability to promote cellular cholesterol efflux. RESULTS: After 3 months of treatment with tocilizumab, HAQ (- 23%, p < 0.05), DAS28 (- 49%, p < 0.001), and hsCRP (- 94%, p < 0.01) levels decreased significantly. Total cholesterol (TC), LDL-C, non-HDL-C, and apo B levels showed a significant increase after treatment (TC: + 7.0%, p < 0.01; LDL-C: + 10%, p < 0.01; non-HDL-C: + 9.9%, p < 0.01; and apo B: + 9.6%, p < 0.05). Decreases in Lp(a) and OxLDL levels were also observed after treatment [Lp(a): - 50%, p < 0.01; and oxLDL: - 5.4%, p < 0.05]. The latter was in accordance with the increment detected in PON activity. No changes were observed in HDL capacity to promote cholesterol efflux (p > 0.05) in the whole group. CONCLUSIONS: Treatment with tocilizumab reduced hsCRP levels and displayed positive effects on certain lipoprotein-related parameters, such as a potent decrease inLp(a) and a reduction in OxLDL levels. Moreover, HDL capacity to promote cellular cholesterol efflux was maintained after 3 months of treatment.

Adherence to Treatment with Tofacitinib in Patients with Rheumatoid Arthritis in Daily Clinical Practice. / Adherencia al tratamiento con tofacitinib en pacientes con artritis reumatoide en la práctica clínica diaria.

OBJECTIVES: To evaluate the adherence to treatment with tofacitinib in patients with rheumatoid arthritis (RA) using two versions of the self-questionnaire Compliance Questionnaire Rheumatology, CQR19 and CQR5, to determine the variables associated with adherence to tofacitinib and to compare the performance of both questionnaires. MATERIAL AND METHODS: A cross-sectional study was carried out. We included patients ≥18years old, with RA (ACR/EULAR criteria 2010) under treatment with tofacitinib. Sociodemographic data, clinical characteristics, treatment and data on patient evaluation. All the patients completed self-questionnaires CQR19 and CQR5. STATISTICAL ANALYSIS: Descriptive statistics. T-test or Mann Whitney to compare the continuous variables, chi2 test or Fisher's exact test for the categorical ones. Kappa concordance index. Multiple logistic regression. RESULTS: We included 52 patients, 82.7% women, with a median (m) age of 57.7years, disease duration m 16years, 63.5% had comorbidities. Of the patients, 86.5% were treated with tofacitinib (5mg BID) and 48% received tofacitinib as monotherapy. The median time of tofacitinib treatment was 13months, 42.3% suspended treatment, and only one patient permanently stopped treatment due to lack of provision. Median CQR19 was 89.5%, and 84.6% had an adherence ≥80%. The variables significantly associated with adherence ≥80% were the presence of comorbidities (P=.014) and older age (P=.033). Considering the CQR5, a similar percentage of patients (82.7%) were adherents to treatment, however, the concordance with CQR19 was low. In the multivariate analysis, older age was the only variable independently associated with good adherence to treatment. CONCLUSIONS: Treatment adherence to tofacitinib was very good for both presentations. Older age was associated with higher adherence. The agreement between the questionnaires CQR19 and CQR5 was low.

Validación del índice ReXSPA (Reductive X-ray Score for Psoriatic Arthritis) en pacientes con Artritis Psoriásica de la cohorte RAPSODIA / Validation of the ReXSPA index (Reductive X-ray Score for Psoriatic Arthritis) in patients with Psoriatic arthritis of the RAPSODIA cohort

Existen diversos índices capaces de valorar el daño radiográfico en pacientes con artritis psoriásica (APs), sin embargo la mayoría fueron creados para su uso en Artritis Reumatoidea y luego modificados para APs, por lo tanto no valoran lesiones características como la osteoproliferación. El objetivo de este estudio fue validar el Reductive X-Ray Score for Psoriatic Arthritis (ReXSPA), el cual fue recientemente desarrollado para su uso en cohortes observacionales. Material y métodos: Estudio de corte transversal, en el cual se incluyeron pacientes ≥18 años de edad, en forma consecutiva, con diagnóstico de APs según criterios CASPAR. A todos los pacientes se les realizaron radiografías de manos y pies en proyección anteroposterior. Dos lectores ciegos para las características clínicas de los pacientes y previamente entrenados, analizaron las mismas por medio de los índices Sharp van der Heijde modificado para APs (SvdHmAPs) y ReXSPA. Se midió el tiempo empleado para la lectura de los índices radiográficos y para el cálculo de los mismos. Resultados: Se incluyeron 66 pacientes, 50% mujeres, con tiempo de evolución de la APs mediano de 8 años (RIC: 4-14.3). 132 radiografías fueron evaluadas según los índices SvdHmAPs [m 35 (RIC: 16.3-72.5)] y el ReXSPA [m 22 (RIC: 7-46.3)]. El tiempo para la lectura radiográfica fue significativamente menor para ReXSPA comparado con SvdHmAPs [media 5.8±2.1 vs media 7.5±2.5 minutos, p<0.0001], al igual que el tiempo para calcularlo [media 26.5±14.7 vs media 55.3±38.3 segundos, p<0.0001]. La correlación entre estos últimos fue excelente (Rho: 0.93). En el análisis multivariado se observó asociación de ambos índices con el tiempo de evolución de la enfermedad y en el caso de ReXSPA también con la edad. Conclusión: El índice ReXSPA ha demostrado validez y una excelente correlación con el índice SvdHmAPs, con menor tiempo para su lectura y cálculo. Evaluaciones longitudinales posteriores permitirán demostrar la validez de estos hallazgos.

There are many scores available to measure radiographic joint damage in patients with Psoriatic Arthritis (PsA), but most of them were developed for Rheumatoid Arhtritis and then modified for PsA. These scores do not evaluate juxtaarticular bone proliferation. The aim of our study was to validate the Reductive X-Ray Score for Psoriatic Arthritis (ReXSPA), which was recently developed to be used in observational cohorts. Methods: A cross-sectional study was carried out. Consecutive patients ≥18 years old with PsA according to CASPAR criteria were included. All patients underwent X-rays of the hands and feet in an anteroposterior view. Two blind readers for the clinical characteristics of the patients and previously trained, scored them by Sharp van der Heijde modified for PsA (PsA-SvdH) and ReXSPA indexes. Time to read and calculate both scores were measured. Results: A total of 66 patients were included, half of them were female, median (m) disease duration of 8 years (IQR: 4-14.3). 132 X-Rays were scored according to PsA-SvdH [m 35 (IQR: 16.3-72.5)] and ReXSPA [m 22 (IQR: 7-46.3)]. Time to read was significantly shorter for ReXSPA than PsA-SvdH [mean 5.8±2.1 vs mean 7.5±2.5 minutes, p<0.0001], as well as, time to calculate them [mean 26.5±14.7 vs mean 55.3±38.3 seconds, p<0.0001]. The correlation between both indexes was excellent (Rho: 0.93). In the multivariate analysis, using both radiographic scores as dependent variable, association of each of the indices with disease duration was observed, and ReXSPA also had association with age. Conclusion: The ReXSPA index has shown validity and a very good correlation with PsA-SvdH. It is quicker to read and to calculate than PsA-SvdH. Subsequent longitudinal evaluations will allow demonstrating the validity of these findings.

Coastal fish assemblages and predation pressure in northern-central Chilean Lessonia trabeculata kelp forests and barren grounds.

Kelp forests are declining in many parts of the globe, which can lead to the spreading of barren grounds. Increased abundances of grazers, mainly due to reduction of their predators, are among the causes of this development. Here, we compared the species richness (SR), frequency of occurrence (FO), and maximum abundance (MaxN) of predatory fish and their predation pressure between kelp forest and barren ground habitats of northern-central Chile. Sampling was done using baited underwater cameras with vertical and horizontal orientation. Two prey organisms were used as tethered baits, the black sea urchin Tetrapygus niger and the porcelanid crab Petrolisthes laevigatus. SR did not show major differences between habitats, while FO and MaxN were higher on barren grounds in vertical videos, with no major differences between habitats in horizontal videos. Predation pressure did not differ between habitats, but after 24 h consumption of porcelanid crabs was significantly higher than that of sea urchins. Scartichthys viridis/gigas was the main predator, accounting for 82% of the observed predation events on Petrolisthes laevigatus. Most of these attacks occurred on barren grounds. Scartichthys viridis/gigas was the only fish observed attacking (but not consuming) tethered sea urchins. High abundances of opportunistic predators (Scartichthys viridis/gigas) are probably related to low abundances of large predatory fishes. These results suggest that intense fishing activity on large predators, and their resulting low abundances, could result in low predation pressure on sea urchins, thereby contributing to the increase of T. niger abundances in subtidal rocky habitats.

Changing rate of serious infections in biologic-exposed rheumatoid arthritis patients. Data from South American registries BIOBADABRASIL and BIOBADASAR.

OBJECTIVE: Most reports on serious infections (SI) in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) are from the USA and Western Europe. Data from other regions are largely missing. We report data from South American countries with different backgrounds and health-care systems but similar registries. METHODS: We merged 2010-2016 data from two registries, BIOBADABRASIL (Brazil) and BIOBADASAR (Argentina), which share the same protocol, online platform and data monitoring process. Patients with active RA were included when they began the first bDMARD or a conventional synthetic DMARD (csDMARD, control group). The SI incidence rate (IR) per 1000 patient/years and adjusted IR ratio (aIRR) were estimated for bDMARDs and csDMARDs. RESULTS: Data were analysed for 3717 RA patients with an exposure of 13,380 patient/years. The 2591 patients treated with bDMARDs (64% tumour necrosis factor-α inhibitors (TNFi)) had a follow-up of 9300 years, and the 1126 treated with csDMARDs had an exposure of 4081 patient/years. The SI IR was 30.54 (CI 27.18-34.30) for all bDMARDs and 5.15 (CI 3.36-7.89) for csDMARDs. The aIRR between the two groups was 2.03 ([1.05, 3.9] p = 0.034) for the first 6 months of treatment but subsequently increased to 8.26 ([4.32, 15.76] p < 0.001). The SI IR for bDMARDs decreased over time in both registries, dropping from 36.59 (28.41-47.12) in 2012 to 7.27 (4.79-11.05) in 2016. CONCLUSION: While SI remains a major concern in South American patients with RA treated with bDMARDs, a favourable trend toward a reduction was observed in the last years.Key Points• New comprehensive data on biologic drugs safety from international collaboration in South America.• First proposal for national registries data merging in South America.• Serious infections remain a major concern in RA patients treated with biologics.• A significant reduction of serious infections in RA patients exposed to biologics was observed over a 7 years period.

Frequency of human leukocyte antigens class II-DR alleles (HLA-DRB1) in Argentinian patients with early arthritis.

Patients with rheumatoid arthritis (RA) or undifferentiated arthritis (UA) in the CONAART database (Argentine Consortium for Early Arthritis) were assessed for genetic risk factors for RA, specifically for HLA-DRB1 alleles and the PTPN22 rs2476601 polymorphism associated with progression to RA. This is a case-control study. Blood samples were obtained to determine HLA-DRB1 genotypes by PCR-SSO Luminex and PTPN22 (rs2476601) polymorphism by allelic discrimination. A control group of individuals from the general Argentinian population were obtained from the national register of cadaveric organ donors. A total of 1859 individuals were included in this analysis: 399 patients from the CONAART database (347 patients with RA at study end and 52 patients with UA at study end, mean follow-up time 25 ± 18 months) and 1460 individuals from the general Argentinian population. Compared with the controls, the HLA-DRB1*04 and DRB1*09 alleles were more commonly detected in patients with RA diagnosis (OR (95% CI) 2.23 (1.74-2.85) and 1.89 (1.26-2.81)) respectively. Both patients with UA and the general population showed higher frequency of DRB1*07, DRB1*11 and DRB1*15 alleles than patients with RA. PTPN22 rs2476601 polymorphism frequency was higher in RA and UA vs the general population; however, this was significantly different only for RA vs control group (OR [95% CI] = 1.81 [1.10-3.02], P = 0.018. HLA-DRB1 typing and PTPN22 allelic discrimination could distinguish between patients with UA, patients with early RA, and the general population in Argentina. This is the first study of HLA-DRB1 alleles and PTPN22 polymorphism associations with progression to early RA in an Argentinian population.

Tuberculin test conversion in patients with chronic inflammatory arthritis receiving biological therapy.

OBJECTIVE: The blockade of inflammatory mediators produced by biological therapies is associated with an increased risk of opportunistic infections, as for example Mycobacterium tuberculosis (MT). Given the endemic situation of tuberculosis (TB) in some countries and immunosuppression/anergy of patients with chronic inflammatory arthritis, we wonder whether it is necessary to monitor the MT infection after starting the biological treatment. To evaluate the frequency of the tuberculin skin test (TST) conversion and its association with an active TB infection and other disease variables. METHODS: Patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and spondyloarthritis (SpA) receiving treatment with anti-TNF, tocilizumab, and/or abatacept agents were included into the study. Patients had to have a negative TST (<5 mm) at the baseline, and a second TST was performed 2-22 months after the initiation of biologic therapy. The TST conversion was considered as a variation ≥5 mm between the two TSTs performed within an interval between 2 months and 2 years. RESULTS: A total of 85 patients were included into the study, and 78.8% were women, with a median schooling duration of 12 years. A total of 74.1% of patients had RA, 16.5% psoriatic arthritis, and 4.7% AIJ and ankylosing spondylitis. Regarding treatment, 75.3% received anti-TNF therapy (31.8% etanercept, 21.2% adalimumab, 17.6% infliximab, 3.5% golimumab, and 1.2% certolizumab), 15.3% tocilizumab, and 9.4% abatacept. Eight patients (9.4%) developed a TST conversion. The shift was more frequent in men (62.5%) than in women (37.5%) (p=0.009), and in those with a prolonged disease duration (X 226±109 vs X130±105 [p=0.017]). This association remained after adjusting for other variables. All patients who developed a TST conversion received prophylactic isoniazid, and only one patient with other risk factors developed active TB. CONCLUSION: The frequency of a TST conversion in patients with chronic inflammatory arthritis was low and was associated with male gender and longer disease duration.

Viraje tuberculínico en pacientes con artritis inflamatorias crónicas y terapia biológica / Tuberculin test conversión in patients with chronic inflammatory arthritis and biological therapy

Introducción: El bloqueo de los mediadores inflamatorios producido por las terapias biológicas se asocia a un aumento de las infecciones oportunistas, como infección por Mycobacterium tuberculosis (MT), por lo que se recomienda realizar intradermorreacción de derivado proteico purificado (PPD) antes de iniciar dicho tratamiento. Teniendo en cuenta la situación endémica de tuberculosis (TBC) en nuestro país y la inmunosupresión/anergia de los pacientes con artritis inflamatorias crónicas, nos planteamos si es necesario monitorear la infección de MT luego de iniciado el tratamiento biológico. Objetivos: Evaluar la frecuencia de viraje de PPD y la asociación del viraje con infección activa por MT u otras variables. Materiales y métodos: Se incluyeron pacientes con Artritis Reumatoidea (AR), Artritis Idiopática Juvenil (AIJ) y Espondiloartritis (EsP) en tratamiento con agentes Anti-TNFα, Tocilizumab y/o Abatacept. Los pacientes debían tener una PPD negativa (<5 mm) basal y una segunda PPD realizada entre los 2 y 22 meses posteriores. Se consignaron datos sociodemográficos (edad, género, estatus social, hacinamiento), antecedentes patológicos (desnutrición, alcoholismo, tuberculosis y sus contactos), tipo de enfermedad reumática y tiempo de evolución, índices de actividad (RAPID-3, BASDAI), de función (BASFI, HAQ-II) y tratamiento concomitante con corticoides (CT), drogas modificadoras de la enfermedad (DME) y terapia biológica (TB). Se consideró viraje de PPD a una variación ≥ a 5 mm entre dos pruebas realizadas con intervalo entre 2 meses y 2 años. En caso de viraje se recomendó seguimiento por Neumonología e Infectología. Análisis estadístico: las variables categóricas se compararon por Chi2 y test exacto de Fisher y las continuas por T-test o Mann-Whitney. Regresión logística múltiple. Resultados: Se incluyeron 85 pacientes, 78,8% eran mujeres, con una escolaridad mediana de 12 años. El 98,8% tenía residencia urbana, 12,9% tenía criterios de hacinamiento y 8,2% ingresos inferiores a la línea de pobreza. 5,9% de los pacientes había padecido TBC con cumplimiento de tratamiento completo y 2,4% reportó contactos con TBC. En cuanto al tipo de artropatía inflamatoria crónica, el 74,1% de los pacientes tenían AR, el 16,5% Artritis Psoriásica (APs) y 4,7% tanto AIJ como Espondilitis Anquilosante. Con respecto al tratamiento, 18,8% recibía más de 10 mg diarios de esteroides orales, el 91,8% DME, (84,7% Metotrexato y 21,2% Leflunomida). El 75,3% recibía terapia Anti-TNFα (31,8% Etanercept, 21,2% Adalimumab, 17,6% Infliximab, 3,5% Golimumab y 1,2% Certolizumab), el 15,3% Tocilizumab y el 9,4% Abatacept. De los 85 pacientes, 8 viraron (9,4%). El viraje fue más frecuente en varones 62,5% vs mujeres 37,5% (p=0,009) y en aquellos con mayor tiempo de evolución de enfermedad en meses [X226±109 vs X130±105 (p=0,017)]. Esta asociación se mantuvo luego de ajustar para otras variables. Todos los pacientes que presentaron viraje recibieron isoniacida (INH) profiláctica y sólo un paciente, con factores de riesgo, desarrolló tuberculosis activa. Conclusión: La frecuencia del viraje tuberculínico en pacientes con artritis inflamatorias crónicas fue baja y se asoció a sexo masculino y mayor tiempo de evolución de la enfermedad

Nest-building behavior by the amphipod Peramphithoe femorata (Kroyer) on the kelp Macrocystis pyrifera (Linnaeus) C. Agardh from Northern-Central Chile.

Many small arthropod herbivores from terrestrial and marine environments construct tubicolous nest-like domiciles on their host plants or algae by rolling up selected portions of the leaf or blade. Nests serve as both shelter and food, which results in conflicting needs for the grazers because feeding activity continuously destroys parts of the nests. While the nesting habit of ampithoid amphipods and other peracarid crustaceans is widely known, very little is known about the nest dynamics and how the conflict between shelter and food requirements is resolved. Herein we examined the nest-building behavior and nest occupancy of the kelp-dwelling amphipod Peramphithoe femorata on the giant kelp Macrocystis pyrifera. Domiciles on the distal-most part of the blades were occupied by amphipods and were steadily advanced toward the blade base. Since the blades grow from a basal growth meristem, blades and nests develop in opposite directions. Thus, the amphipods exploit the kelp growth pattern to maintain their nests in the medium-distal part of the blades. During a 2-week-long experiment, we observed that blade elongation equaled nest advancement during the first 8 days after nest construction. Thereafter, blade growth slowed down and was surpassed by nest advancement rates, possibly forcing amphipods to seek out new blades. Nest occupancy was generally short (1-4 days), but some amphipods resided longer (>4 days) in their nests. The sophisticated nest-building behavior of P. femorata and other ampithoids maximizes nest persistence, offers optimal protection against predators, and promotes feeding on nutritive or, alternatively, on less defended tissues.

Conceptos emergentes de tolerancia y autoinmunidad: Nuevos enfoques terapéuticos / Tolerance and autoimmunity: Novel therapeutic approaches

La función primaria del sistema inmune es resguardar al individuo de los patógenos potencialmente dañinos que invaden el medio ambiente en el cual nos desarrollamos. Este cuenta con dos grandes ramas, la inmunidad innata y la adaptativa, ambas con la propiedad de diferenciar lo peligroso de aquello inofensivo. Estos procesos se hallan regulados por mecanismos homeostáticos que constituyen la tolerancia inmunológica, a los fines de limitar aquellos procesos prolongados y silenciar los potencialmente autoagresivos. Ante la falla de estos mecanismos de control, surgen las enfermedades autoinmunes. Avances en el conocimiento de la fisiopatología de estas entidades, han abierto un nuevo capítulo en el terreno de la inmunofarmacología. Su prometedor potencial actualmente nos ofrece novedosas herramientas terapéuticas para controlar y atenuar el daño causado por este tipo de respuestas. No obstante, debe continuarse la investigación en el campo de los agentes biológicos, ya que ninguno de ellos se encuentra libre de inconvenientes. Seguramente, futuros hallazgos se concretarán en futuros aciertos. Y los aciertos, en Medicina, equivalen a esperanza.

The main function of the immune system is to protect the individual against potentially dangerous pathogens. It comprises innate and adaptive cellular and soluble components, both with the capacity to discriminate between harmful and harmless. These processes are regulated by homeostatic mechanisms that constitute the so-called immunological tolerance, which aims to limit the prolonged action of immune mediators and to silence the generation of potentially autoaggressive components. Failure to silence self-reactive T and B cells results in the generation of autoimmune disease. Recent advances in our knowledge of these pathological entities have opened a new chapter in the pharmacology of the immune system. Its promising potential currently offers new therapeutic agents to control and attenuate pathological tissue damage. Nevertheless, further research regarding these biologic agents is required, since they are not free from inconveniences. It is without question that upcoming findings in this field will instill hope into the quest for the "magic bullet".

[Tolerance and autoimmunity. Novel therapeutic approaches]. / Conceptos emergentes de tolerancia y autoinmunidad. Nuevos enfoques terapéuticos.

The main function of the immune system is to protect the individual against potentially dangerous pathogens. It comprises innate and adaptive cellular and soluble components, both with the capacity to discriminate between harmful and harmless. These processes are regulated by homeostatic mechanisms that constitute the so-called immunological tolerance, which aims to limit the prolonged action of immune mediators and to silence the generation of potentially autoaggressive components. Failure to silence self-reactive T and B cells results in the generation of autoimmune disease. Recent advances in our knowledge of these pathological entities have opened a new chapter in the pharmacology of the immune system. Its promising potential currently offers new therapeutic agents to control and attenuate pathological tissue damage. Nevertheless, further research regarding these biologic agents is required, since they are not free from inconveniences. It is without question that upcoming findings in this field will instill hope into the quest for the "magic bullet".