Severe infections in systemic necrotizing vasculitis.

Infections in patients with systemic vasculitis represent one of the main causes of mortality. Corticosteroid use, immunosuppressive therapy, age, associated organic involvement and dialysis dependence are risk factors of infection. OBJECTIVES: To determine the prevalence of severe infection and associated factors in patients diagnosed with ANCA-associated vasculitis (AAV) and Polyarteritis Nodosa (PAN). METHODS: retrospective study was conduced in a single rheumatology center (2000-2018). We included patients diagnosed with AAV (Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA) and Microscopic Polyangiitis (PAM) and Polyarteritis nodosa (PAN). Serious infectious events requiring hospitalisation or prolonged antibiotic/antiviral treatment, recurrent infection of Herpes Zoster Virus or opportunistic infections were evaluated. Sites of infection, isolated microorganisms and mortality related were analyzed. RESULTS: 105 patients were analyzed, follow-up time median 18 m, 58.7% were women and median age was 52 years. Types of vasculitis: 41.9% PAM, 16.2% EPGA, 40% GPA, 1.9% PAN. Constitutional, pulmonary, renal and otorhinolaryngology manifestations were the most frequent. PREVALENCE OF INFECTION: 34.2%, with a median of 3 months from diagnosis of vasculitis to the infectious event. Low respiratory tract (42.8%), sepsis (31.4%), and urinary tract (14.3%) were the most common sites of infections. Bacterial aetiology was the most prevalent (67.7%). Mortality at the first event was 14.3% and a 72.2% of patients were in the induction phase of treatment. Infectious events were significantly associated with age > 65 years (p = 0.030), presence of lung (p = 0.016) and renal involvement (p = 0.001), BVASv3 > 15, mortality (p = 0.0002). CONCLUSIONS: The prevalence of infection was 34.2%. Lower airway infections, septicemia and urinary tract infections were the most prevalent. Infections were associated with renal and pulmonary involvement, age older than 65 years and score BVAS > 15. Severe infections were associated with mortality, especially in elderly patients.

Designer TALEs enable discovery of cell death-inducer genes.

Transcription activator-like effectors (TALEs) in plant-pathogenic Xanthomonas bacteria activate expression of plant genes and support infection or cause a resistance response. PthA4AT is a TALE with a particularly short DNA-binding domain harboring only 7.5 repeats which triggers cell death in Nicotiana benthamiana; however, the genetic basis for this remains unknown. To identify possible target genes of PthA4AT that mediate cell death in N. benthamiana, we exploited the modularity of TALEs to stepwise enhance their specificity and reduce potential target sites. Substitutions of individual repeats suggested that PthA4AT-dependent cell death is sequence specific. Stepwise addition of repeats to the C-terminal or N-terminal end of the repeat region narrowed the sequence requirements in promoters of target genes. Transcriptome profiling and in silico target prediction allowed the isolation of two cell death inducer genes, which encode a patatin-like protein and a bifunctional monodehydroascorbate reductase/carbonic anhydrase protein. These two proteins are not linked to known TALE-dependent resistance genes. Our results show that the aberrant expression of different endogenous plant genes can cause a cell death reaction, which supports the hypothesis that TALE-dependent executor resistance genes can originate from various plant processes. Our strategy further demonstrates the use of TALEs to scan genomes for genes triggering cell death and other relevant phenotypes.

Results and prognosis of kidney transplantation in lupus nephritis: Experience of an Argentine center.

INTRODUCTION: Although RT has improved the survival of the population with ESRD due to all causes, renal outcomes in SLE are controversial. The objective of this study is to describe the characteristics and evolution of the patients and the kidney transplant in LN, and compare it with patients transplanted for other causes. MATERIALS AND METHODS: Retrospective, observational, analytical, single-center study in which records of patients undergoing nephrotransplantation for LN were analyzed. They were compared with a group of patients transplanted at the same center for other causes of ESRD. RESULTS: 41 patients with kidney transplant due to SLE and 89 transplanted due to other causes of ESRD were registered. Graft loss occurred in 12 (29.26%) patients with LN and 34 (38.2%) patients in the comparison group (p = .428). Only one case (4.8%) presented reactivation of the LN in the graft, without graft loss. Median graft survival was 73.1 months in the LN group and 66.3 months in the comparison group (p = .221). A total of 8 (19.5%) patients with LN and 11 (12.4%) without LN died (p = .42), with infections being the main cause in both groups. There were no statistically significant differences between groups in graft and patient survival. In a sub-analysis of 28 patients with LN with aPL study, 4 thrombotic events were observed, in 3 different patients, in the aPL-positive group. There were no statistically significant differences in terms of causes of graft loss and graft survival (positive aFL 75.7 months vs negative aFL 72.7 months, p= .96). There were also no differences in mortality between the groups (p = .61). CONCLUSION: Patients transplanted for LN did not differ from the control population in terms of graft and patient survival. Infections were the main cause of death, so prophylaxis and vaccination continue to be a fundamental pillar in the prevention of infections in immunocompromised patients.

Manifestaciones oftalmológicas en vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos: análisis retrospectivo de 104 pacientes en un centro de referencia en Argentina / Ophthalmological manifestations in anti-neutrophil cytoplasmic antibodies associated vasculitis: retrospective analysis of 104 patients in a reference center in Argentina

Resumen Introducción: el compromiso oftalmológico (CO) en las vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos (VAA) varía ampliamente según el subtipo de vasculitis. Objetivos: describir la frecuencia, las formas clínicas y los factores asociados del CO en pacientes con VAA al inicio de la enfermedad. Materiales y métodos: estudio retrospectivo, observacional y analítico, de centro único, que incluyó pacientes con VAA a los cuales se los dividió en dos grupos según la presencia o ausencia de CO al inicio de la enfermedad. Se realizó estadística descriptiva, análisis bivariado y multivariado para evaluar los factores asociados al CO. Resultados: se incluyeron 104 pacientes, 64 (61,5%) eran mujeres. El 49% pertenecía al grupo de granulomatosis con poliangitis (GPA), el 34,6% a poliangitis microscópica (PAM) y el 16,3% a granulomatosis eosinofílica con poliangitis (GEPA). Del total, 30 (28,8%) presentaron CO al inicio de la vasculitis (47% en GPA, 17,6% en GEPA y 8,33% en PAM). El compromiso orbitario se observó exclusivamente en los pacientes con GPA. En el análisis multivariado, las variables que se mantuvieron asociadas de manera independiente al CO en el debut de la enfermedad fueron la elevación de la eritrosedimentación y la trombocitosis. Se observaron secuelas en 9 (30%) de los pacientes con CO. Conclusiones: la frecuencia y la forma clínica del CO dependen del tipo de VAA. Debido a su alta frecuencia y también a la posibilidad de secuelas posteriores, resulta importante su rápida identificación y tratamiento adecuado.

Abstract Introduction: ophthalmological involvement (OI) in vasculitis associated with anti-neutrophil cytoplasmic antibodies (AAV) varies widely depending on the subtype of vasculitis. Objectives: to describe the frequency, clinical manifestations, and ophthalmological sequelae as well as factors associated with ophthalmological involvement in patients with ANCA-associated vasculitis (AAV). Materials and methods: a retrospective and analytical study in patients with AAV was performed. OI was recorded at the beginning of the disease, and patients were divided into two groups according to the presence or absence of OI. Descriptive statistics, bivariate and multivariate analysis were performed to evaluate the factors associated with OI. Results: one hundred and four patients with AAV were included, and 61.5% were women. Forty-nine percent of patients presented granulomatosis with polyangiitis (GPA), 34.6% microscopic polyangiitis (MPA), and 16.3% eosinophilic granulomatosis with polyangiitis (EGPA). Of the total, 30 patients (28.8%) presented OI at the beginning of the disease (47% GPA, 17.6% EGPA and 8.33% MPA). The orbital commitment was observed exclusively in patients with GPA. In the multivariate analysis, erythrosedimentation and thrombocytosis showed an association with OI. Ophthalmological sequelae were observed in 9 (30%) patients with OI. Conclusions: the frequency and clinical manifestations of OI depend on the type of AAV. Because the frequency and the possibility of subsequent sequelae are high, prompt identification and appropriate treatment are necessary.

Active lupus in Argentina: Results of a multicenter and national registry.

OBJECTIVE: To evaluate the association between patients' characteristics and disease activity in an Argentine lupus registry. METHODS: Cross-sectional study. Disease activity was stratified into: Remission off-treatment: SLEDAI = 0, without prednisone and immunosuppressive drugs. Low disease activity Toronto Cohort (LDA-TC): SLEDAI ≤2, without prednisone or immunosuppressive drugs. Modified lupus low disease activity (mLLDAS): SLEDAI score of ≤4, with no activity in major organ systems and no new features, prednisone of ≤10 mg/day and/or immunosuppressive drugs (maintenance dose) and Active disease: SLEDAI score of >4 and prednisone >10 mg/day and immunosuppressive drugs. A descriptive analysis and logistic regression model were performed. RESULTS: A total of 1346 patients were included. Of them, 1.6% achieved remission off steroids, 0.8% LDA-TC, 12.1% mLLDAS and the remaining 85.4% had active disease. Active disease was associated with younger age (p ≤ 0.001), a shorter time to diagnosis (p ≤ 0.001), higher frequency of hospitalizations (p ≤ 0.001), seizures (p = 0.022), serosal disease (p ≤ 0.001), nephritis (p ≤ 0.001), higher SDI (p ≤ 0.001), greater use of immunosuppressive therapies and higher doses of prednisone compared to those on mLLDAS. In the multivariable analysis, the variables associated with active disease were the presence of pleuritis (OR 2.1, 95% CI 1.2-3.9; p = 0.007), persistent proteinuria (OR 2.5, 95% CI 1.2-5.5; p ≤ 0.011), nephritis (OR 2.5, 95% CI 1.2-5.6; p = .018) and hospitalizations (OR 8.9, 95% CI 5.3-16.0; p ≤ 0.001) whereas age at entry into the registry was negatively associated with it (OR 0.9, 95% CI 0.9-1.0; p = 0.029). CONCLUSION: Active disease was associated with shorter time to diagnosis, worse outcomes (SDI and hospitalizations) and renal, neurological and serosal disease.

Frecuencia de eventos cardiovasculares en pacientes con lupus eritematoso sistémico / Frequency of cardiovascular events in patients with systemic lupus erythematosus

Resumen Introducción: el progreso en los tratamientos para el lupus eritematoso sistémico (LES) resultó en una disminución de la mortalidad; sin embargo, la enfermedad cardiovascular y las complicaciones infecciosas aún son las principales causas de muerte. La evidencia apoya la participación del sistema inmunológico en la generación de la placa aterosclerótica, así como su conexión con las enfermedades autoinmunes. Objetivos: describir la frecuencia de eventos cardiovasculares (ECV) en el Registro de Lupus Eritematoso Sistémico de la Sociedad Argentina de Reumatología (RELESSAR) transversal, así como sus principales factores de riesgo asociados. Materiales y métodos: estudio descriptivo y transversal para el cual se tomaron los pacientes ingresados en el registro RELESSAR transversal. Se describieron las variables sociodemográficas y clínicas, las comorbilidades, score de actividad y daño. ECV se definió como la presencia de al menos una de las siguientes patologías: enfermedad arterial periférica, cardiopatía isquémica o accidente cerebrovascular. El evento clasificado para el análisis fue aquel posterior al diagnóstico del LES. Se conformaron dos grupos macheados por edad y sexo 1:2. Resultados: 1515 pacientes mayores de 18 años participaron del registro. Se describieron 80 pacientes con ECV (5,3%). En este análisis se incluyeron 240 pacientes conformando dos grupos. La edad media fue de 47,8 (14,4) y 47,6 (14,2) en el grupo con y sin ECV respectivamente. Los pacientes con ECV tuvieron mayor duración del LES en meses, mayor índice de Charlson, mayor SLICC (Systemic Lupus International Collaborating Clinics/American College of Rheumatology), mayor frecuencia de manifestaciones neurológicas, síndrome antifosfolípido, hospitalizaciones y uso de ciclofosfamida. Las únicas variables asociadas en el análisis multivariado fueron el índice de Charlson (p=0,004) y el SLICC (p<0,001). Conclusiones: los ECV influyen significativamente en nuestros pacientes, y se asocian a mayor posibilidad de daño irreversible y comorbilidades.

Abstract Introduction: progress in treatments for systemic lupus erythematosus (SLE) has resulted in a decrease in mortality; however, cardiovascular and infectious diseases remain the leading causes of death. Evidence supports the involvement of the immune system in the generation of atherosclerotic plaque, as well as its connection to autoimmune diseases. Objectives: to describe the frequency of cardiovascular disease (CVD) in the cross-sectional RELESSAR registry, as well as its associated variables. Materials and methods: a descriptive and cross-sectional study was performed using patients admitted to the cross-sectional RELESSAR registry. Sociodemographic variables, clinical variables, comorbidities, activity and damage scores were described. CVD was defined as at least one of the following: peripheral arterial disease, ischemic heart disease, or cerebrovascular accident. All patients with at least one CVD were included in our analysis (heart attack, central nervous system vascular disease, and peripheral arteries atherosclerotic disease). The event classified for the analysis was that after the diagnosis of SLE. SLE diagnosis was previous to CVD. Two groups matched by age and sex, 1:2 were formed. Results: a total of 1515 patients older than 18 years participated in the registry. Eighty patients with CVD (5.3%) were described in the registry. Two-hundred and forty patients were included, according to two groups. The mean age was 47.8 (SD 14.4) and 47.6 (SD 14.2) in patients with and without CVD, respectively. Patients with CVD had a longer duration of SLE in months, a higher Charlson index, a higher SLICC, increased frequency of neurological manifestations, antiphospholipid syndrome, hospitalizations, and use of cyclophosphamide. The associated variables in the multivariate were the Charlson Index (p=0.004) and the SLICC (p<0.001). Conclusions: CVDs have a significant influence on our patients, being associated with a greater possibility of damage and comorbidities.

Cutaneous manifestations in patients with systemic lupus erythematosus: Forms at the beginning of the disease and during follow-up. Retrospective analysis.

OBJECTIVES: To describe skin involvement (SI) in patients with systemic lupus erythematosus (SLE) at onset and during follow-up of the disease and to determine factors associated with SI at lupus diagnosis. MATERIALS AND METHODS: Retrospective, observational, and descriptive study, from a single centre in patients diagnosed with SLE (ACR 1982-97 or SLICC 2012 criteria). The modified Gilliam classification for SI was used. Descriptive statistics and bivariate and multivariate analysis were performed to evaluate the factors associated with SI at diagnosis of the disease. RESULTS: 149 patients were included, 91.3% women with a median age at diagnosis of 33 years. SI at onset of the disease occurred in 125 patients (83.9%), followed by joint involvement in 120 cases (80.5%). Non-specific skin lesions were more frequent than specific lesions, 92.8% versus 66.4%, respectively. In the bivariate analysis, a longer delay to diagnosis, the presence of joint involvement, a lower presence of thrombocytopenia, and a higher SLEDAI-2K score were associated with the presence of SI at onset of the disease. In the multivariate analysis, the variable that remained independently associated was joint involvement (OR 2.8%-95% CI 1.1-7.5, p: .04). During follow-up, 4/24 patients who had not presented SI at diagnosis and 51/125 patients who had, had at least one new skin flare (range: 1-5 outbreaks). CONCLUSIONS: Our study demonstrates the high frequency of skin involvement in SLE, both diagnostically and evolutionarily, and confirms previously reported data regarding the existence of a skin-articular phenotype.

Priming crop plants with rosemary (Salvia rosmarinus Spenn, syn Rosmarinus officinalis L.) extract triggers protective defense response against pathogens.

Plant bioactive compounds provide novel straightforward approaches to control plant diseases. Rosemary (Salvia rosmarinus)-derived extracts carry many prominent pharmacological activities, including antimicrobial and antioxidant, mainly due to its phenolic compounds, rosmarinic acid (RA), carnosic acid and carnosol. However, the effects of these extracts on plant diseases are still unknown, which constrains its potential application as bioprotectant in the agricultural production. In this study we demonstrate the antiviral effect of the aqueous rosemary extract (ARE) against tobacco necrosis virus strain A (TNVA) in ARE-treated tobacco (Nicotiana tabacum) plants. Our results show that ARE-treatment enhances plant defense response, contributing to reduce virus replication and systemic movement in tobacco plants. RA, the main phenolic compound detected in this extract, is one of the main inducers of TNVA control. The ARE-induced protection in TNVA-infected plants was characterized by the expression of H2O2 scavengers and defense-related genes, involving salicylic acid- and jasmonic acid-regulated pathways. Furthermore, treatment with ARE in lemon (Citrus limon) and soybean (Glycine max) leaves protects the plants against Xanthomonas citri subsp. citri and Diaporthe phaseolorum var. meridionalis, respectively. Additionally, ARE treatment also promotes growth and development, suggesting a biostimulant activity in soybean. These results open the way for the potential use of ARE as a bioprotective agent in disease management.

Validation of an indirect in-house ELISA using synthetic peptides to detect antibodies anti-gp90 and gp45 of the equine infectious anaemia virus.

BACKGROUND: Equine infectious anaemia (EIA) is controlled by the identification of seropositive animals. The official diagnostic method is the agar gel immunodiffusion (AGID) test, which detects antibodies against a viral core protein (p26). Although AGID is inexpensive and specific, the report of results takes considerable time and the test has low analytical sensitivity. OBJECTIVE: To validate our in-house indirect ELISAgp90/45 , following the World Organization of Animal Health (OIE) criteria. STUDY DESIGN: Test validation. METHODS: Synthetic peptides gp90 and gp45 were used as antigens in ELISAgp90/45 . Tests used for validation, calibration and linear working operating range, analytical and diagnostic sensitivity and specificity, repeatability and reproducibility were assessed by comparing them with the AGID test and using 1844 equine sera grouped into five different panels. RESULTS: We were able to replace the National References Sera with our Internal Reference Sera. ELISAgp90/45 had acceptable repeatability and reproducibility. Analytical sensitivity of the ELISAgp90/45 was 800 times greater than that of AGID test for positive sera and 400 times greater for weak positive sera. ELISAgp90/45 also showed optimal analytical specificity, since no cross-reactivity was detected with antibodies against other equine viruses. One sample was positive by AGID test and negative by ELISAgp90/45. ELISAgp90/45 was performed using 243 EIA positive and 878 negative equid sera, and showed a diagnostic sensitivity of 99.59% [CI 97.73%-99.99%] and a diagnostic specificity of 90.32% [CI 88.17%-92.19%], compared to AGID test; thus, it was demonstrated to be a robust test. MAIN LIMITATIONS: Samples were derived from naturally infected equid populations showing heterogeneous clinical states: therefore, their status was uncertain and some horses were sampled more than once. The AGID test may not be the most useful gold standard. CONCLUSION: ELISAgp90/45 is a useful tool for the diagnosis of EIAV infection and meets validation requirements established by the OIE.

A serralysin-like protein of Candidatus Liberibacter asiaticus modulates components of the bacterial extracellular matrix.

Huanglongbing (HLB), the current major threat for Citrus species, is caused by intracellular alphaproteobacteria of the genus Candidatus Liberibacter (CaL), with CaL asiaticus (CLas) being the most prevalent species. This bacterium inhabits phloem cells and is transmitted by the psyllid Diaphorina citri. A gene encoding a putative serralysin-like metalloprotease (CLIBASIA_01345) was identified in the CLas genome. The expression levels of this gene were found to be higher in citrus leaves than in psyllids, suggesting a function for this protease in adaptation to the plant environment. Here, we study the putative role of CLas-serralysin (Las1345) as virulence factor. We first assayed whether Las1345 could be secreted by two different surrogate bacteria, Rhizobium leguminosarum bv. viciae A34 (A34) and Serratia marcescens. The protein was detected only in the cellular fraction of A34 and S. marcescens expressing Las1345, and increased protease activity of those bacteria by 2.55 and 4.25-fold, respectively. In contrast, Las1345 expressed in Nicotiana benthamiana leaves did not show protease activity nor alterations in the cell membrane, suggesting that Las1345 do not function as a protease in the plant cell. Las1345 expression negatively regulated cell motility, exopolysaccharide production, and biofilm formation in Xanthomonas campestris pv. campestris (Xcc). This bacterial phenotype was correlated with reduced growth and survival on leaf surfaces as well as reduced disease symptoms in N. benthamiana and Arabidopsis. These results support a model where Las1345 could modify extracellular components to adapt bacterial shape and appendages to the phloem environment, thus contributing to virulence.

Taller de concordancia en la evaluación de imágenes capilaroscópicas / Reliability of nailfold videocapillaroscopy workshop

Introducción: la capilaroscopia es un método no invasivo que permite observar la microvasculatura en el área periungueal. Los resultados informados pueden ser altamente variables entre distintos observadores. A lo largo del tiempo surgieron métodos cuantitativos y semicuantitativos para mejorar la reproducibilidad. Objetivos: conocer el nivel de acuerdo intra e interobservador al informar los diferentes patrones capilaroscópicos en individuos con diferente nivel de entrenamiento. Materiales y métodos: estudio de corte transversal. Participaron médicos reumatólogos especialistas y en formación que habían realizado previamente un curso virtual de capacitación en capilaroscopia. Recibieron 40 imágenes capilaroscópicas proyectadas en una presentación de PowerPoint y debían responder a través de un cuestionario digital. Se evaluó la concordancia de respuestas intra e interobservador. Resultados: se encontró un alto nivel de concordancia global con un kappa 0,66 IC 95% (0,63-0,70) p<0,0000. También en otros grupos como reumatólogos en formación: kappa 0,65 IC 95% (0,60-0,71) p=0,0000, y médicos reumatólogos: kappa 0,67 IC 95% (0,62-0,72) p=0,0000. Conclusiones: el nivel de concordancia encontrado fue globalmente alto, independientemente del nivel de entrenamiento de los profesionales, y de ser o no reumatólogo. La concordancia fue superior cuando se comparó a quienes tenían más de 4 años de experiencia en la realización de videocapilaroscopia.

Introduction: videoapillaroscopy is a non-invasive method that allows the observation of the microvasculature in the periungual area. Reported results can be highly variable between different observers. Over time, quantitative and semi-quantitative methods emerged to improve reproducibility. Objetives: to know the level of intra and interobserver agreement when reporting the different capillaroscopic patterns in individuals with different levels of training. Materials and methods: cross section study. Specialist rheumatologists and those in training who had previously completed a virtual capillaroscopy training course participated. They received 40 capillaroscopic images projected in a PowerPoint presentation and had to issue their response through a digital questionnaire. Concordance of intra and interobserver responses was evaluated. Results: a high level of global agreement was found with a kappa 0.66 CI 95% (0.63-0.70) p<0.0000, also in other groups such as rheumatologists in training: kappa 0.65 CI 95% (0.60-0.71) p=0.0000, physicians rheumatologists: kappa 0.67 95% CI (0.62-0.72) p=0.0000. Conclusions: the level of agreement found was globally high, regardless of the level of training of the professionals, and whether or not they were a rheumatologist. Concordance was higher when compared to those who had more than 4 years of experience performing videocapillaroscopy.

An Argentinean cohort of patients with rheumatic and immune-mediated diseases vaccinated for SARS-CoV-2: the SAR-CoVAC Registry-protocol and preliminary data.

BACKGROUND/OBJECTIVE: To evaluate the efficacy and safety of SARS-CoV-2 vaccine in patients with rheumatic and immune-mediated inflammatory diseases (IMIDs) in Argentina: the SAR-CoVAC registry. METHODS: SAR-CoVAC is a national, multicenter, and observational registry. Adult patients with rheumatic or IMIDs vaccinated for SARS-CoV-2 were consecutively included between June 1 and September 17, 2021. Sociodemographic data, comorbidities, underlying rheumatic or IMIDs, treatments received, their modification prior to vaccination, and history of SARS-CoV-2 infection were recorded. In addition, date and place of vaccination, type of vaccine applied, scheme, adverse events (AE), disease flares, and new immune-mediated manifestations related to the vaccine were analyzed. RESULTS: A total of 1234 patients were included, 79% were female, with a mean age of 57.8 (SD 14.1) years. The most frequent diseases were rheumatoid arthritis (41.2%), osteoarthritis (14.5%), psoriasis (12.7%), and spondyloarthritis (12.3%). Most of them were in remission (28.5%) or low disease activity (41.4%). At the time of vaccination, 21% were receiving glucocorticoid treatment, 35.7% methotrexate, 29.7% biological (b) disease modifying anti-rheumatic drugs (DMARD), and 5.4% JAK inhibitors. In total, 16.9% had SARS-CoV-2 infection before the first vaccine dose. Most patients (51.1%) received Gam-COVID-Vac as the first vaccine dose, followed by ChAdOx1 nCoV-19 (32.8%) and BBIBP-CorV (14.5%). Half of them (48.8%) were fully vaccinated with 2 doses; 12.5% received combined schemes, being the most frequent Gam-COVID-Vac/mRAN-1273. The median time between doses was 51 days (IQR 53). After the first dose, 25.9% of the patients reported at least one AE and 15.9% after the second, being flu-like syndrome and local hypersensitivity the most frequent manifestations. There was one case of anaphylaxis. Regarding efficacy, 63 events of SARS-CoV-2 infection were reported after vaccination, 19% occurred during the first 14 days post-vaccination, 57.1% after the first dose, and 23.8% after the second. Most cases (85.9%) were asymptomatic or mild and 2 died due to COVID-19. CONCLUSIONS: In this national cohort of patients, the most common vaccines used were Gam-COVID-Vac and ChAdOx1 nCoV-19. A quarter of the patients presented an AE and 5.1% presented SARS-CoV-2 infection after vaccination, in most cases mild. STUDY REGISTRATION: This study has been registered in ClinicalTrials.gov under the number: NCT04845997. Key Points • This study shows real-world data about efficacy and safety of SARS-CoV-2 vaccination in patients with rheumatic and immune-mediated inflammatory diseases. Interestingly, different types of vaccines were used including vector-based, mRNA, and inactivated vaccines, and mixed regimens were enabled. • A quarter of the patients presented an adverse event. The incidence of adverse events was significantly higher in those receiving mRAN-1273 and ChAdOx1 nCoV-19. • In this cohort, 5.1% presented SARS-CoV-2 infection after vaccination, in most cases mild.

Lupus en Argentina. Pacientes no respondedores al tratamiento estándar y belimumab como posible opción. Datos del registro RELESSAR / Lupus in Argentina. Non-responders to standard treatment and belimumab as a possible option. RELESSAR record data

Introducción: el lupus es una enfermedad compleja y varias veces de difícil abordaje. Alcanzar la remisión es uno de los objetivos, incorporando opciones terapéuticas. Objetivos: describir las características generales de los pacientes según el estado de la enfermedad y el uso de belimumab. Materiales y métodos: estudio de corte transversal, registro RELESSAR. Se definió el estado de la enfermedad como: remisión: SLEDAI=0 y sin corticoides; baja actividad de la enfermedad: SLEDAI >0 y ≤4 y sin corticoides; control no óptimo: SLEDAI >4 y cualquier dosis de corticoides. Resultados: se incluyeron 1.277 pacientes, 23,4% en remisión, 12,6% en baja actividad y 63,8% con control no óptimo. En este último grupo eran más jóvenes y con menor duración de la enfermedad; presentaban mayores índices de actividad y cronicidad, y mayor empleo de inmunosupresores. Solo el 22,3% de los pacientes con criterio potencial de uso de belimumab (lupus eritematoso sistémico activo a pesar del tratamiento estándar) lo recibía en ese momento. Las variables asociadas a hospitalizaciones fueron: terapia con corticoides, ciclofosfamida y mayor SLICC. Conclusiones: se refleja la complejidad del manejo de estos pacientes y se visualizan aspectos estructurales como la desigualdad. El uso del belimumab resultaría beneficioso en los pacientes seleccionados.

Introduction: lupus is a complex disease and often difficult to approach. Achieving remission is one of the objectives, incorporating therapeutic options. Objectives: to describe the characteristics of the patients and the use of belimumab, according to the status of the disease. Materials and methods: cross-sectional study. Patients of the RELESSAR registry. Stratification: Remission: SLEDAI=0 and without corticosteroids. Low disease activity SLEDAI> 0 and ≤4 and without corticosteroids and non-optimal control: SLEDAI> 4 and any dose of corticosteroids. Results: a total of 1,277 patients were included, 23.4% in remission, 12.6% in low disease activity and 63.8% in non-optimal control. The last group was younger and had a shorter duration of the disease. They had higher activity and chronicity indices and greater use of immunosuppressants. Only 22.3% of the patients with potential criteria for the use of belimumab (activity disease despite standard treatment) were receiving it. The variables associated with hospitalizations were: corticosteroids, cyclophosphamide and higher SLICC. Those associated with severe infection: mycophenolate mofetil, azathioprine, corticosteroids, and higher SLICC. Conclusions: the complexity of the management of these patients is reflected, visualizing structural aspects such as inequality. The use of belimumab could be beneficial in selected patients.

Consenso de inmunizaciones en adultos con enfermedades reumáticas inflamatorias crónicas autoinmunes / Consensus on immunizations in adults with autoimmune chronic inflammatory rheumatic diseases

Aumento del riesgo de infecciones prevenibles y sus complicaciones en pacientes con enfermedades reumáticas inflamatorias crónicas (ERICA), con y sin tratamiento con inmunosupresores (IS), y beneficios de la vacunación.

Lupus en Argentina. Pacientes no respondedores al tratamiento estándar y belimumab como posible opción. Datos del registro RELESSAR / Lupus in Argentina. Non-responders to standard treatment and belimumab as a possible option. RELESSAR record data

Introducción: el lupus es una enfermedad compleja y varias veces de difícil abordaje. Alcanzar la remisión es uno de los objetivos, incorporando opciones terapéuticas. Objetivos: describir las características generales de los pacientes según el estado de la enfermedad y el uso de belimumab. Materiales y métodos: estudio de corte transversal, registro RELESSAR. Se definió el estado de la enfermedad como: remisión: SLEDAI=0 y sin corticoides; baja actividad de la enfermedad: SLEDAI >0 y ≤4 y sin corticoides; control no óptimo: SLEDAI >4 y cualquier dosis de corticoides. Resultados: se incluyeron 1.277 pacientes, 23,4% en remisión, 12,6% en baja actividad y 63,8% con control no óptimo. En este último grupo eran más jóvenes y con menor duración de la enfermedad; presentaban mayores índices de actividad y cronicidad, y mayor empleo de inmunosupresores. Solo el 22,3% de los pacientes con criterio potencial de uso de belimumab (lupus eritematoso sistémico activo a pesar del tratamiento estándar) lo recibía en ese momento. Las variables asociadas a hospitalizaciones fueron: terapia con corticoides, ciclofosfamida y mayor SLICC. Conclusiones: se refleja la complejidad del manejo de estos pacientes y se visualizan aspectos estructurales como la desigualdad. El uso del belimumab resultaría beneficioso en los pacientes seleccionados.

Introduction: lupus is a complex disease and often difficult to approach. Achieving remission is one of the objectives, incorporating therapeutic options. Objectives: to describe the characteristics of the patients and the use of belimumab, according to the status of the disease. Materials and methods: cross-sectional study. Patients of the RELESSAR registry. Stratification: Remission: SLEDAI=0 and without corticosteroids. Low disease activity SLEDAI> 0 and ≤4 and without corticosteroids and non-optimal control: SLEDAI> 4 and any dose of corticosteroids. Results: a total of 1,277 patients were included, 23.4% in remission, 12.6% in low disease activity and 63.8% in non-optimal control. The last group was younger and had a shorter duration of the disease. They had higher activity and chronicity indices and greater use of immunosuppressants. Only 22.3% of the patients with potential criteria for the use of belimumab (activity disease despite standard treatment) were receiving it. The variables associated with hospitalizations were: corticosteroids, cyclophosphamide and higher SLICC. Those associated with severe infection: mycophenolate mofetil, azathioprine, corticosteroids, and higher SLICC. Conclusions: the complexity of the management of these patients is reflected, visualizing structural aspects such as inequality. The use of belimumab could be beneficial in selected patients.

'Candidatus Liberibacter asiaticus' Multimeric LotP Mediates Citrus sinensis Defense Response Activation.

'Candidatus Liberibacter asiaticus' is known as the most pathogenic organism associated with citrus greening disease. Since its publicized emergence in Florida in 2005, 'Ca. L. asiaticus' remains unculturable. Currently, a limited number of potential disease effectors have been identified through in silico analysis. Therefore, these potential effectors remain poorly characterized and do not fully explain the complexity of symptoms observed in citrus trees infected with 'Ca. L. asiaticus.' LotP has been identified as a potential effector and have been partially characterized. This protein retains structural homology to the substrate binding domain of the Lon protease. LotP interacts with chaperones like GroEL, Hsp40, DnaJ, and ClpX and may exercise its biological role through interactions with different proteins involved in proteostasis networks. Here, we evaluate the interactome of LotP-revealing a new protein-protein interaction target (Lon-serine protease) and its effect on citrus plant tissue integrity. We found that via protein-protein interactions, LotP can enhance Lon protease activity, increasing the degradation rate of its specific targets. Infiltration of purified LotP strained citrus plant tissue causing photoinhibition and chlorosis after several days. Proteomics analysis of LotP tissues recovering after the infiltration revealed a large abundance of plant proteins associated with the stabilization and processing of mRNA transcripts, a subset of important transcription factors; and pathways associated with innate plant defense were highly expressed. Furthermore, interactions and substrate binding module of LotP suggest potential interactions with plant proteins, most likely proteases.

Vasculitis cutáneas: etiología y características clínicas en pacientes adultos en un centro de tercer nivel / Cutaneous vasculitis: etiology and clinical characteristics in adult patients at a third-level center

Introducción: Diversas entidades clínicas, como enfermedades autoinmunes, infecciones, neoplasias y fármacos pueden manifestarse con lesiones vasculíticas en la piel. Debido a la heterogeneidad de las causas, suelen representar un desafío diagnóstico. El objetivo de este estudio es describir la etiología de las vasculitis cutáneas (VC) y evaluar las características clínicas, histológicas y de laboratorio halladas en estos pacientes. Material y métodos: Se realizó un estudio retrospectivo con revisión de historias clínicas de pacientes mayores de 16 años con VC por diagnóstico clínico y/o histológico evaluados en el período 2010-2018. Resultados: Se incluyeron 74 pacientes. El 69% son mujeres con una edad media al diagnóstico de 41 años (DE 16.5, rango 16-75). Las causas más frecuentes asociadas a las VC fueron las enfermedades autoinmunes (EAI) en un 50% de los pacientes evaluados. En el 29.7% de los casos no pudo identificarse una causa subyacente. En el 2.7% de los casos se asoció a neoplasias, otro 2.7% a fármacos y un 12% a otras etiologías. El 76% de los pacientes presentaron formas clínicas no severas, predominando la púrpura palpable en el 65% de los casos. Entre los pacientes biopsiados, el 76% fueron vasculitis leucocitoclásticas (VLC). Como manifestaciones extracutáneas asociadas, predominó el compromiso articular (43,2%). En las vasculitis asociadas a EAI, el 33 % presentó compromiso renal, en tanto que éste no se observó en ninguno de los pacientes con vasculitis idiopáticas. El 78% de los pacientes recibieron glucocorticoides sistémicos. Conclusión: En nuestro centro, la etiología más común de VC fue la asociada a EAI. La mayoría de los pacientes eran mujeres. Clínicamente predominaron las manifestaciones cutáneas no severas y la VLC fue el hallazgo más frecuente en las biopsias.

Background: Various clinical entities, such as autoimmune diseases, infections, neoplasms and drugs can manifest with vasculitic lesions on the skin. Due to the heterogeneity of causes, they often represent a diagnostic challenge. The aim of this study is to describe the etiology of cutaneous vasculitis (CV) and to assess the clinical, histological and laboratory characteristics found in these patients. Material and methods: A retrospective study was carried out with a review of the medical records of patients over 16 years old with CV by clinical and/or histological diagnosis evaluated in the period 2010-2018. Results: 74 patients were included. 69% are women with a mean age at diagnosis of 41 years (SD 16.5, range 16-75). The most frequent causes associated with CVs were autoimmune diseases (AID) in 50% of the patients evaluated. In 29.7% of the cases, an underlying cause could not be identified. In 2.7% of the cases it was associated with neoplasms, another 2.7% with drugs, and 12% with other etiologies. 76% of the patients presented non-severe clinical forms, with palpable purpura predominant in 65% of the cases. Among the biopsied patients, 76% were leukocytoclastic vasculitis (LCV). As associated extracutaneous manifestations, joint involvement predominated (43.2%). In vasculitis associated with AID, 33% presented renal involvement, while this was not observed in any of the patients with idiopathic vasculitis. 78% of the patients received systemic glucocorticoids. Conclusion: In our center, the most common etiology of CV was associated with AID. Most of the patients were women. Clinically, non-severe skin manifestations predominated and VLC was the most frequent finding in biopsies.

Validation of the adjusted global antiphospholipid syndrome score in systemic lupus erythematosus patients in Argentina.

INTRODUCTION: Assessment of risk both for pregnancy morbidity and thrombosis in the presence of anti-phospholipid antibodies (aPL) is still a challenge in Systemic Lupus Erythematosus (SLE) patients. The Global Antiphospholipid Syndrome Score (GAPSS) takes into account the aPL profile (criteria and non-criteria aPL), the conventional cardiovascular risk factors and the autoimmune antibody profile. An adjusted model of the score (aGAPSS) excluding anti-phosphatidylserine/Prothrombin (aPS/PT), suggests that the score is able to stratify patients for their rate of events making it widely applicable in daily clinical practice. OBJECTIVE: To validate the aGAPSS in a multicentric cohort of SLE patients in Argentina. PATIENTS AND METHODS: consecutive SLE patients with and with andwithout thrombotic events from seven Rheumatologist centers were included. Traditional cardiovascular risk factors, aPL antibodies and medications received (aspirin, hydroxychloroquine and anticoagulation) were collected. The score aGAPSS was calculated for each patient at the last visit by adding together the points corresponding to the risk factors: 1 for hypertension, 3 for dyslipidemia, 4 for LA and B2GPI (IgM or IgG) antibodies and 5 for aCL (IgM or IgG) antibodies. The discriminative ability of the aGAPSS was calculated by measuring the area under the receiver operating characteristic curve (AUC). Multivariate logistic regression analysis was performed to examine the impact of multiple cardiovascular risk factors and laboratory parameters on the occurrence of thrombosis. RESULTS: Two hundred and ninety-six SLE patients were included. One-hundred and twenty-one patients (40.9%) presented thrombotic and/or pregnancy complications. Median aGAPSS was significantly higher in patients who experienced an event (thrombosis and/or pregnancy morbidity) compared with those without [4 (IQR 1-9) versus 1 (IQR 0-5); p < 0.001]. The best cut off point for the diagnosis of thrombosis and/or pregnancy complications was aGAPSS ≥4. Multivariate logistic regression analysis showed that aCL antibodies [OR 2.1 (95% CI 1.16-3.90); p = 0.015] were an independent risk factors for thrombotic events. CONCLUSIONS: This score is a simple tool, easy to apply to SLE patients in daily practice. The use of the aGAPSS could change the non-pharmacologic and pharmacologic treatment in higher risk patients to improve their survival.

PthA4AT , a 7.5-repeats transcription activator-like (TAL) effector from Xanthomonas citri ssp. citri, triggers citrus canker resistance.

Transcription activator-like effectors (TALEs) are important effectors of Xanthomonas spp. that manipulate the transcriptome of the host plant, conferring susceptibility or resistance to bacterial infection. Xanthomonas citri ssp. citri variant AT (X. citri AT ) triggers a host-specific hypersensitive response (HR) that suppresses citrus canker development. However, the bacterial effector that elicits this process is unknown. In this study, we show that a 7.5-repeat TALE is responsible for triggering the HR. PthA4AT was identified within the pthA repertoire of X. citri AT followed by assay of the effects on different hosts. The mode of action of PthA4AT was characterized using protein-binding microarrays and testing the effects of deletion of the nuclear localization signals and activation domain on plant responses. PthA4AT is able to bind DNA and activate transcription in an effector binding element-dependent manner. Moreover, HR requires PthA4AT nuclear localization, suggesting the activation of executor resistance (R) genes in host and non-host plants. This is the first case where a TALE of unusually short length performs a biological function by means of its repeat domain, indicating that the action of these effectors to reprogramme the host transcriptome following nuclear localization is not limited to 'classical' TALEs.

The mitochondrial oxidation resistance protein AtOXR2 increases plant biomass and tolerance to oxidative stress.

This study demonstrates the existence of the oxidation resistance (OXR) protein family in plants. There are six OXR members in Arabidopsis that contain the highly conserved TLDc domain that is characteristic of this eukaryotic protein family. AtOXR2 is a mitochondrial protein able to alleviate the stress sensitivity of a yeast oxr1 mutant. It was induced by oxidative stress and its overexpression in Arabidopsis (oeOXR2) increased leaf ascorbate, photosynthesis, biomass, and seed production, as well as conferring tolerance to methyl viologen, antimycin A, and high light intensities. The oeOXR2 plants also showed higher ABA content, changes in ABA sensitivity, and modified expression of ABA- and stress-regulated genes. While the oxr2 mutants had a similar shoot phenotype to the wild-type, they exhibited increased sensitivity to stress. We propose that by influencing the levels of reactive oxygen species (ROS), AtOXR2 improves the efficiency of photosynthesis and elicits basal tolerance to environmental challenges that increase oxidative stress, allowing improved plant growth and biomass production.