B-Cell Activation Biomarkers in Salivary Glands Are Related to Lymphomagenesis in Primary Sjögren's Disease: A Pilot Monocentric Exploratory Study.

Primary Sjögren's disease is primarily driven by B-cell activation and is associated with a high risk of developing non-Hodgkin's lymphoma (NHL). Over the last few decades, microRNA-155 (miR-155) has arisen as a key regulator of B-cells. Nevertheless, its role in primary Sjögren's disease remains elusive. Thus, the purpose of this study was (i) to explore miR-155, B-cell activating factor (BAFF)-receptor (BAFF-R), and Interleukin 6 receptor (IL-6R) expression in the labial salivary glands (LSG) of patients with primary Sjögren's disease, aiming to identify potential B-cell activation biomarkers related to NHL development. Twenty-four patients with primary Sjögren's disease, and with available tissue blocks from a LSG biopsy performed at diagnosis, were enrolled. Among them, five patients developed B-cell NHL during follow-up (7.3 ± 3.1 years). A comparison group of 20 individuals with sicca disease was included. Clinical and laboratory parameters were recorded and the LSG biopsies were evaluated to assess local inflammation in terms of miR-155/BAFF-R and IL-6R expression. Stratifying the primary Sjögren's disease cohort according to lymphomagenesis, miR-155 was upregulated in primary Sjögren's disease patients who experienced NHL, more so than those who did not experience NHL. Moreover, miR-155 expression correlated with the focus score (FS), as well as BAFF-R and IL-6R expression, which were increased in primary Sjögren's disease patients and in turn related to neoplastic evolution. In conclusion, epigenetic modulation may play a crucial role in the aberrant activation of B-cells in primary Sjögren's disease, profoundly impacting the risk of NHL development.

Intensive training programme for ultrasound-guided minimally invasive synovial tissue biopsy on knees and wrists in different phases of inflammation.

OBJECTIVES: To develop an intensive training programme for ultrasound (US)-guided synovial tissue (ST) biopsy on knees and wrists in inflammatory arthritis and to assess the learning curve, patient tolerability, sample quality and trainees' expectations. METHODS: Active or remission rheumatoid arthritis patients were enrolled. Nine trainees joined the 4-month programme in a centre experienced in performing US-guided ST biopsies consisting of four sequential phases: (1) observation, (2) performance of guided step-by-step phases, (3) execution of the whole procedure on paired joints (knees or wrists) of the same patient in parallel with the trainer and (4) performance of the procedure autonomously. Sample representativity was assessed by histology, and procedure-related adverse events were recorded. Before and after the programme, trainees' expectations and perceptions were collected. RESULTS: 328 ST biopsy procedures were included. The rate of trainees' informative samples was: (1) comparable to the trainers in active and remission knees, but lower in active wrists (70% for trainees vs 100% for trainers, p=0.06) in phase 3; (2) excellent on active knees and wrists (91.9% and 90.9% respectively) but lower (77.6%, p=0.0089) on remission knees in phase 4. Procedures performed by trainees did not affect patient tolerability. Trainees' expectations about procedure-related invasiveness and pain infliction decreased while the difficulty of procedure execution on active wrists and remission knees remained perceived as moderately difficult. CONCLUSIONS: This intensive training programme develops advanced skills in the performance of US-guided ST biopsy on knees and wrists, yielding high-quality specimens available for basic and translational studies on inflammatory joint diseases.

Serum Albumin Levels: A Biomarker to Be Repurposed in Different Disease Settings in Clinical Practice.

Serum albumin (ALB), one of the most important proteins in human physiology, has the main functions of maintaining plasma oncotic pressure and plasma volume, transporting hormones, vitamins, oligominerals and drugs, and exerting a powerful antioxidant-anti-inflammatory role. Its prognostic value in liver and malabsorption syndromes is well known. In this narrative review, an analysis of the most important studies evaluating the prognostic significance of low serum ALB levels in hospitalized patients was performed. Specifically, the risk in emergency medicine, cardiovascular diseases, Coronavirus Disease 19 (COVID-19) infection, nephrology, oncology, and autoimmune rheumatic diseases has been examined to fully explore its clinical value. ALB is a negative acute-phase reactant and the reduction in its serum levels represents a threatening parameter for long-term survival in several clinical settings, and a strong biomarker for a poor prognosis in most diseases. Therefore, clinicians should consider serum ALB as a valuable tool to assess the efficacy of specific therapies, both in hospitalized patients and in chronic follow-up.

COVID-19 illness: Different comorbidities may require different immunological therapeutic targets.

BACKGROUND: The SARS-CoV-2 pandemic has led to more than 6,870.000 deaths worldwide. Despite recent therapeutic advances, deaths in Intensive Care Units still range between 34 and 72%, comprising substantial unmet need as we move to an endemic phase. The general agreement is that in the first few days of infection, antiviral drugs and neutralizing monoclonal antibodies should be adopted. When the patient is hospitalized and develops severe pneumonia, progressing to a systemic disease, immune modifying therapy with corticosteroids is indicated. Such interventions, however, are less effective in the context of comorbidities (e.g., diabetes, hypertension, heart failure, atrial fibrillation, obesity and central nervous system-CNS diseases) which are by themselves associated with poor outcomes. Such comorbidities comprise common and some distinct underlying inflammatory pathobiology regulated by differential cytokine taxonomy. METHODS: Searching in the PubMed database, literature pertaining to the biology underlying the different comorbidities, and the data from the studies related to various immunological treatments for the Covid-19 disease were carefully analyzed. RESULTS: Several experimental and clinical data have demonstrated that hypertension and atrial fibrillation present an IL-6 dependent signature, whereas diabetes, obesity, heart failure and CNS diseases may exhibit an IL-1a/b predominant signature. Distinct selective cytokine targeting may offer advantage in treating severe COVID-19 illness based on single or multiple associated comorbidities. When the patient does not immediately respond, a broader target range through JAKs pathway inhibitors may be indicated. CONCLUSIONS: Herein, we discuss the biological background associated with distinct comorbidities which might impact the SARS-CoV-2 infection course and how these should to be addressed to improve the current therapeutic outcome.

The forgotten key players in rheumatoid arthritis: IL-8 and IL-17 - Unmet needs and therapeutic perspectives.

Despite the relevant advances in our understanding of the pathogenetic mechanisms regulating inflammation in rheumatoid arthritis (RA) and the development of effective therapeutics, to date, there is still a proportion of patients with RA who do not respond to treatment and end up progressing toward the development of joint damage, extra-articular complications, and disability. This is mainly due to the inter-individual heterogeneity of the molecular and cellular taxonomy of the synovial membrane, which represents the target tissue of RA inflammation. Tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) are crucial key players in RA pathogenesis fueling the inflammatory cascade, as supported by experimental evidence derived from in vivo animal models and the effectiveness of biologic-Disease Modifying Anti-Rheumatic Drugs (b-DMARDs) in patients with RA. However, additional inflammatory soluble mediators such as IL-8 and IL-17 exert their pathogenetic actions promoting the detrimental activation of immune and stromal cells in RA synovial membrane, tendons, and extra-articular sites, as well as blood vessels and lungs, causing extra-articular complications, which might be excluded by the action of anti-TNFα and anti-IL6R targeted therapies. In this narrative review, we will discuss the role of IL-8 and IL-17 in promoting inflammation in multiple biological compartments (i.e., synovial membrane, blood vessels, and lung, respectively) in animal models of arthritis and patients with RA and how their selective targeting could improve the management of treatment resistance in patients.

From Bench to Bedside in Rheumatoid Arthritis from the "2022 GISEA International Symposium".

While precision medicine is still a challenge in rheumatic disease, in recent years many advances have been made regarding pathogenesis, the treatment of inflammatory arthropathies, and their interaction. New insight into the role of inflammasome and synovial tissue macrophage subsets as predictors of drug response give hope for future tailored therapeutic strategies and a personalized medicine approach in inflammatory arthropathies. Here, we discuss the main pathogenetic mechanisms and therapeutic approaches towards precision medicine in rheumatoid arthritis from the 2022 International GISEA/OEG Symposium.

Infectious agents breaking the immunological tolerance: The holy grail in rheumatoid arthritis reconsidered.

Multiple Sclerosis (MS) has been shown to be linked to Epstein Barr Virus (EBV) infection, a virus that infects B cells inside the CNS. The seminal study raises a key interest into the infectious origin of several other autoimmune inflammatory diseases.We will discuss here the infectious agents that have been studied over the years in Rheumatoid Arthritis (RA), a crippling arthritis that was treated a century ago with gold salts (anti mycobacterial agent), chloroquine (anti malarial agent), or sulphasalazine (an antibacterial-antiinflammatory agent). Several infectious agents have been taken into consideration, i.e. Streptococcus group A, Proteus, Mycobacterium tuberculosis-MTB, Parvovirus B19, Epstein Barr virus, Porphyromonas gingivalis-Pg, Aggregatibacter actinomycetescomitans, and finally Haemophilus-Glaesserella parasuis-Hps. Of these agents only three satisfy the Witebski's criteria as possible pathogenetic causes of an autoimmune disease, i.e. MTB, Pg, Hps. We will discuss here how the immune tolerance might be broken, which could be the neoantigen or autoantigen involved, how the infectious agent was studied as a trigger capable of inducing arthritis in animal models. The preventive measures that should be adopted to lessen the impact of the infections, to prevent the burden and the severity of the illness are described.

Simultaneous Onset of Mycobacterium kansasii Pulmonary Infection and Systemic Lupus Erythematosus: A Case Report.

BACKGROUND Systemic lupus erythematosus (SLE) is a systemic autoimmune disease resulting from dysregulation of the immune response. In genetically predisposed subjects, infections reputedly trigger an immune activation leading to autoimmunity and overt autoimmune diseases such as SLE. CASE REPORT We report the case of a 19-year-old woman who presented to our hospital reporting high-grade fever, dry cough, and polyarthralgia despite a course of empiric antibiotic and steroid therapy administered by her general practitioner (GP). On physical examination, she had a malar rash, a palpable erythematous maculopapular non-itchy rash over the limbs and trunk, and mild polyarthritis. A contrast computed tomography (CT) scan of the chest showed a pulmonary right upper-lobe consolidation with air bronchogram and multiple necrotizing conglomerate mediastinal lymph nodes. Culturing of collected samples from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of the mediastinal lymph node revealed growth of Mycobacterium kansasii. Antinuclear antibodies (ANA) and lupus anticoagulant (LAC) were positive. A diagnosis of M. kansasii infection associated with SLE was made. She was started on anti-mycobacterial and hydroxychloroquine therapy and entered into a joint rheumatological and infectious disease follow-up. Six months later, a CT scan with positron emission tomography (PET) showed a significant reduction in size of the basal right upper-lobe consolidation and hypermetabolic activity in multiple pulmonary areas and mediastinal lymph nodes. ANA and LAC tests were repeated and remained positive. The decision was made to continue the ongoing therapy course for 1 year in total. CONCLUSIONS Clinical and experimental studies have suggested the association of mycobacterial infections with SLE and as a possible infectious trigger of autoimmunity. We describe a unique case of M. kansasii infection associated with the onset of SLE in a young woman.

Systemic Bone Density at Disease Onset Is Associated With Joint Erosion Progression in Early Naive to Treatment Rheumatoid Arthritis: A Prospective 12-Month Follow-Up Open-Label Study.

Objectives: Osteoporosis and bone erosions are hallmarks of rheumatoid arthritis (RA) since disease onset is underpinned by the inflammatory burden. In this observational study, we aimed to dissect the putative RA-related parameters and bone-derived biomarkers associated with systemic and focal bone loss at disease onset and with their progression. Methods: One-hundred twenty-eight patients with early rheumatoid arthritis (ERA) were recruited at disease onset. At study entry, demographic, clinical, and immunological parameters were recorded. Each ERA patient underwent plain X-rays of the hands and feet at study entry and after 12 months to assess the presence of erosions. After enrollment, each patient was treated according to the recommendations for RA management and followed up based on a treat-to-target (T2T) strategy. At baseline, blood samples for soluble biomarkers were collected from each patient, and plasma levels of osteoprotegerin (OPG), receptor activator of nuclear factor κB ligand (RANKL), Dickkopf-1 (DKK1), and interleukin 6 (IL-6) were assessed by enzyme-linked immunosorbent assay (ELISA). Seventy-one ERA patients underwent bone mineral density (BMD) measurement at the left femoral neck and second to fourth lumbar spine vertebrae (L2-L4) by dual-energy X-ray absorptiometry (DXA). Results: Among the whole cohort, 34 (26.6%) ERA patients with bone erosions at study entry had a higher disease activity (p = 0.02) and IL-6 plasma levels (p = 0.03) than non-erosive ones. Moreover, at DXA, 33 (46.5%) ERA patients had osteopenia, and 16 (22.5%) had osteoporosis; patients with baseline bone erosions were more likely osteopenic/osteoporotic than non-erosive ones (p = 0.03), regardless of OPG, RANKL, and DKK1 plasma levels. Obese ERA patients were less likely osteopenic/osteoporotic than normal weight ones (p = 0.002), whereas anti-citrullinated protein antibodies (ACPA) positive ERA patients were more likely osteopenic/osteoporotic than ACPA negative ones (p = 0.034). At logistic regression analysis, baseline Disease Activity Score measured on 44 joints (DAS44) [OR: 2.46 (1.11-5.44)] and osteopenic/osteoporosis status [OR: 7.13 (1.27-39.94)] arose as independent factors of erosiveness. Baseline osteopenic/osteoporotic status and ACPA positivity were associated with bone damage progression during the follow-up. Conclusions: Bone erosions presence is associated with systemic bone loss since the earliest phases of RA, suggesting that the inflammatory burden and autoimmune biology, underpinning RA, represent crucial enhancers of bone remodeling either locally as at systemic level.

Inclusion of Synovial Tissue-Derived Characteristics in a Nomogram for the Prediction of Treatment Response in Treatment-Naive Rheumatoid Arthritis Patients.

OBJECTIVE: This study applied a synovitis score obtained during routine care from ultrasound (US)-guided biopsies of synovial tissue (ST) in patients with rheumatoid arthritis (RA) and patients with other inflammatory and noninflammatory joint diseases to identify pretreatment synovial biomarkers associated with disease characteristics, and to integrate the findings into a multiparameter nomogram for use in baseline prediction of diagnosis and treatment response in treatment-naive rheumatoid arthritis (RA) patients. METHODS: The study enrolled a total of 1,015 patients with various autoimmune diseases (545 patients with RA, 167 patients with psoriatic arthritis [PsA], 199 patients with undifferentiated peripheral inflammatory arthritis [UPIA], 18 patients with crystal-induced arthritis, 26 patients with connective tissue diseases, and 60 patients with osteoarthritis [OA] [as part of the SYNGem cohort]). All patients underwent a US-guided ST biopsy at baseline, and patients were then stratified according to disease phase. The KSS, along with disease characteristics and clinical outcomes, were incorporated into a nomogram for prediction of achievement of clinical remission in RA patients who were previously naive to treatment. In patients in whom a treat-to-target strategy was applied, remission was defined as change in the Disease Activity Score in 28 joints (DAS28) at 6 months after treatment initiation. RESULTS: The KSS significantly differed among RA patients, as well as PsA patients and UPIA patients, when compared to OA patients. In RA, the KSS directly correlated with the DAS28 and was related to autoantibody positivity in treatment-naive RA patients. Moreover, at baseline, treatment-naive RA patients achieving 6-month remission according to DAS28 had a lower KSS, shorter duration of symptoms (very early RA [VERA]), and lower disease activity than treatment-naive RA patients not achieving remission according to DAS28. Results of logistic regression analysis identified the following synergistic predictive factors of achievement of DAS28-based disease remission at 6 months: having a short disease duration (VERA), not having high disease activity, and having a KSS of <5 at baseline. A nomogram integrating these baseline clinical and histologic characteristics in treatment-naive RA patients yielded an up to 81.7% probability of achieving 6-month remission according to the DAS28. CONCLUSION: The KSS is a reliable tool for synovitis assessment on US-guided ST biopsy, contingent on the phase of the disease and the autoimmune profile of each patient. This tool could be integrated within a therapeutic response-predictive nomogram for the prediction of treatment response in RA patients who were previously naive to treatment.

Postural control and disability in patients with early rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) may affect the postural control through abnormal sensory inputs and impaired motor responses. Sensory Organization Test (SOT) objectively evaluates contribution of different sensorial afferences in postural control. The aim of the study is to assess mechanisms of postural instability and their relations with disability and disease characteristics in an early RA(ERA) cohort. METHODS: The equilibrium scores were assessed in 30 ERA patients and 30 age- and sex-matched controls. The somatosensory (SOM), visual (VIS) and vestibular (VEST) ratios were computed to assess the use of different sensory and the composite equilibrium score (CES) as a measure of global balance performance. RESULTS: ERA patients had lower CES (78.4±6.0% vs. 83.4±5.0%, p=0.002), SOM ratio (98.5±1.8% vs. 99.6±2.1%, p=0.035), VIS ratio (85.2±7.6% vs. 91.5±6.0%, p=0.001) and VEST ratio (70.8±10.0% vs. 80.3±7.8%, p<0.001) compared to controls. The presence of ankle arthritis correlated negatively to both SOM (r=-0.369, p=0.045) and VIS ratio (r=0.470, p=0.009), pain severity to CES (r=-0.389, p=0.045) and VIS ratio (r=-0.385, p=0.048) and HAQ-DI to CES (r=-0.591, p=0.001), SOM (r=-0.510, p=0.004) and VIS ratio (r=-0.390, p=0.033.). Patients-reported postural instability was associated with lower CES (75.4±5.4% vs. 80.7±5.5%, p=0.016) and VEST ratios (66.5±10.1% vs. 74.1±8.8%, p=0.036). SOT outcomes did not differ according to acute phase reactants, disease activity or autoantibody positivity. CONCLUSIONS: RA patients showed an early impairment of postural control related to the degree of disability and subjective postural instability. Our data suggest that the lack of balance could result from both impaired motor response and abnormal sensory organisation.

Psoriatic arthritis and depressive symptoms: does systemic inflammation play a role?

OBJECTIVES: Depression is commonly associated with psoriatic arthritis (PsA), but its risk factors in these patients are largely unrecognized. Pro-inflammatory cytokines involved in the pathogenesis of PsA have been associated with depression in patients without autoimmune diseases. The aim of this study was to establish whether PsA patients with and without depressive symptoms differed for general or clinical variables and serum cytokines milieu. METHODS: One hundred and fifty consecutive patients with PsA were screened for depressive symptoms with Hospital Anxiety and Depression Scale (HADS-D). Patients with and without depressive symptoms were compared according to the prevalence of general risk factors for depression, comorbidities, PsA features and serum IL-6, TNF-α, and IL-17A. RESULTS: Fifty-eight patient (38.7%) had a depressive mood. Depressive symptoms were associated with female sex (p = 0.03) and current smoking (p = 0.05). Patients with and without depressive symptoms did not differ for general risk factors for depression and comorbidities. Depressed patients had more frequently psoriatic nail disease (p = 0.02) and significant physical disability (HAQ-DI ≥ 0.5) (p < 0.01) and were more frequently in moderate or high disease activity according to DAPSA score (p = 0.01). Depressed patients had higher serum IL-6 (p < 0.01) and comparable serum IL-17A and TNF-α. A cutoff of 2.27 pg/ml of serum IL-6 had the best ability to predict an HADS-D ≥ 8 (AUC 0.666 ± 0.044; p < 0.01). Multivariate logistic regression analysis confirmed that serum IL-6 ≥ 2.27 pg/ml was independently associated with depressive symptoms (OR 3.5; CI 1.6-7.8; p < 0.01). CONCLUSIONS: Higher serum Il-6 is associated with depressive symptoms. This association suggests a direct role of systemic inflammation in the modulation of mood in PsA patients. Key Points • High PsA disease activity and physical disability are associated with depression. • Higher serum levels of IL-6 are independently associated with depression in PsA. • IL-6 might play a direct role in the development of depression in PsA patients.

Treatment strategy introducing immunosuppressive drugs with glucocorticoids ab initio or very early in giant cell arteritis: A multicenter retrospective controlled study.

OBJECTIVE: Glucocorticoids (GC) are associated with side effects in giant cell arteritis (GCA). Immunosuppressive therapies (ITs) have given conflicting results in GCA, regarding GC sparing effect. Primary endpoint is to evaluate whether very early introduction of ITs in GCA minimize the rate of GC-induced adverse events, in terms of infections, new onset systemic arterial hypertension, GC-induced diabetes and osteoporotic fractures. METHODS: A multicenter retrospective case-control study included 165 patients. One group included 114 patients who were treated with at least one IT given at diagnosis or within 3 months from the start of GC. A second group included 51 GCA who received only GC or an IT more than 3 months later. RESULTS: The most frequently used ITs were: methotrexate (138 patients), cyclophosphamide (48 patients) and tocilizumab (27 patients). No difference was observed as concerns the follow-up time between groups [48.5 (IQR 26-72) vs 40 (IQR 24-69), p â€‹= â€‹0.3)]. The first group showed a significantly lower incidence of steroid-induced diabetes (8/114, 7% vs 12/51, 23.5%; p â€‹= â€‹0.003) and no differences for the rate of infections (p â€‹= â€‹0.64). The group was also exposed to lower doses of GC at first (p â€‹< â€‹0.0001) and third (p â€‹< â€‹0.0001, rank-sum test) month. Forty-four patients in the first group (38.6%) compared with 34 in the second one (66.7%) experienced at least one relapse (p â€‹= â€‹0.001). CONCLUSION: Very early introduction of IT in GCA lowered the incidence of steroid-induced diabetes, possibly due to the lower doses of GC in the first three months. Relapse rate was even lower.

Sarilumab use in severe SARS-CoV-2 pneumonia.

BACKGROUND: Interleukin-6 signal blockade showed preliminary beneficial effects in treating inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Herein we describe the outcomes of off-label intravenous use of Sarilumab in severe SARS-CoV-2-related pneumonia. METHODS: 53 patients with SARS-CoV-2 severe pneumonia received intravenous Sarilumab; pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards, live discharge rate in ICU treated patients and safety profile were recorded. Sarilumab 400 mg was administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and patients were followed for at least 14 days, unless previously discharged or dead. FINDINGS: Of the 53 SARS-CoV-2pos patients receiving Sarilumab, 39(73·6%) were treated in medical wards [66·7% with a single infusion; median PaO2/FiO2:146(IQR:120-212)] while 14(26·4%) in ICU [92·6% with a second infusion; median PaO2/FiO2: 112(IQR:100-141.5)].Within the medical wards, 7(17·9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89·7% of medical inpatients significantly improved (46·1% after 24 h, 61·5% after 3 days), 70·6% were discharged from the hospital and 85·7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64·2% were discharged from ICU to the ward and 35·8% were still alive at the last follow-up. Overall mortality rate was 5·7%. INTERPRETATION: IL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical outcome and good safety.

Differential synovial tissue biomarkers among psoriatic arthritis and rheumatoid factor/anti-citrulline antibody-negative rheumatoid arthritis.

BACKGROUND: Differential diagnosis among psoriatic arthritis (PsA) and seronegative rheumatoid arthritis (Abneg RA) can be challenging particularly in the clinical setting of peripheral phenotype and autoantibodies seronegativity. The aim of the study was to identify synovial tissue (ST) biomarkers differentially expressed in PsA and Abneg RA and test their predictive value of therapeutic response. METHODS: Thirty-four PsA patients [12 DMARD naive and 22 non-responder to methotrexate (MTX-IR)] with peripheral joint involvement and 55 Abneg RA (27 DMARD naive and 28 MTX-IR) underwent US-guided ST biopsy and immunohistochemistry (IHC) for CD68+, CD3+, CD20+, CD21+, CD117+, and CD138+ cells. After study entry, each DMARD-naive patient started MTX therapy and was followed in an outpatient setting for at least 6 months to define the achievement of Minimal Disease Activity (PsA) and DAS remission (Abneg RA) status respectively. Each IR-MTX patient was treated according to EULAR recommendations. RESULTS: At study entry, IHC analysis revealed that PsA patients had comparable levels of lining and sublining CD68+ and sublining CD21+, CD20+, and CD3+ cells than Abneg RA, despite the therapeutic regimen. Moreover, regardless of the therapeutic scheme, PsA patients showed higher IHC score of CD117+ cells (p = 0.0004 and p = 0.0005 for naive and MTX-IR patients respectively) compared to Abneg RA patients. Conversely, Abneg RA patients showed higher IHC score of CD138+ cells, irrespective to the therapeutic scheme (p = 0.04 and p = 0.002 for naive and MTX-IR patients respectively). Analyzing the response rate to the therapeutic scheme, naive PsA patients reaching MDA status at 6 months follow-up, showed, at the study entry, lower IHC score of CD3+ cells compared to PsA patients not reaching this outcome (p = 0.02); conversely, naive Abneg RA patients reaching DAS remission status at 6 months follow-up, showed, at the study entry, lower IHC score of sublining CD68+ cells compared to Abneg RA patients not reaching this outcome (p < 0.001). CONCLUSIONS: CD117+ and CD138+ cells are differentially distributed among PsA and Abneg RA. Histological analysis of ST may help to solve the clinical overlap between the two diseases and provides prognostic data about the therapy success.

Ernesto Weigel Muñoz: precursor de la enseñanza de la Psicología en la Universidad de Buenos Aires / Ernesto Weigel Muñoz: precursor of the teaching of Psychology at the University of Buenos Aires

Abordaremos como eje el Curso de Filosofía dictado a partir de 1894 por Weigel Muñoz en la Facultad de Derecho y Ciencias Sociales de la Universidad de Buenos Aires, situando allí el comienzo de un proceso de desarrollo académico de la Psicología que tiene una continuidad histórica que se corona con la implantación de la psicología experimental por parte de Horacio Piñero en 1902. Entendemos que esta última halla un contexto académico e institucional que posibilita, e incluso demanda su recepción, y que tales condiciones de inscripción se inician con la enseñanza en Derecho por parte de Weigel Muñoz. Consideramos que este curso no es un mero antecedente, sino que posee ya un grado de estructuración que comprende las grandes líneas del pensamiento psicológico vigente e instituye una vertiente discursiva sobre la que se edificará la continuidad del pensamiento psicológico una vez creada la Facultad de Filosofía y Letras.(AU)

We will board as an axis the Philosophy Course dictated from 1894 by Weigel Muñoz at the Faculty of Law and Social Sciences at the University of Buenos Aires, placing there the beginning of a process of academic development of psychology which has a historical continuity that crown with the implantation of the experimental psychology by Horacio Piñero in 1902. We understand that the latter found an academic and institutional context that allows and even demands its reception, and that such conditions of registration will begin with the teaching in law by Weigel Muñoz. We believe that this course is not a mere antecedent, but already has a degree of structure that includes the main lines of current psychological thinking and institutes a discursive dimension which will be built on the continuity of psychological thought once the Faculty of Philosophy and Letters is created.(AU)

Ernesto Weigel Muñoz: precursor de la enseñanza de la Psicología en la Universidad de Buenos Aires / Ernesto Weigel Muñoz: precursor of the teaching of Psychology at the University of Buenos Aires

Abordaremos como eje el Curso de Filosofía dictado a partir de 1894 por Weigel Muñoz en la Facultad de Derecho y Ciencias Sociales de la Universidad de Buenos Aires, situando allí el comienzo de un proceso de desarrollo académico de la Psicología que tiene una continuidad histórica que se corona con la implantación de la psicología experimental por parte de Horacio Piñero en 1902. Entendemos que esta última halla un contexto académico e institucional que posibilita, e incluso demanda su recepción, y que tales condiciones de inscripción se inician con la enseñanza en Derecho por parte de Weigel Muñoz. Consideramos que este curso no es un mero antecedente, sino que posee ya un grado de estructuración que comprende las grandes líneas del pensamiento psicológico vigente e instituye una vertiente discursiva sobre la que se edificará la continuidad del pensamiento psicológico una vez creada la Facultad de Filosofía y Letras.

We will board as an axis the Philosophy Course dictated from 1894 by Weigel Muñoz at the Faculty of Law and Social Sciences at the University of Buenos Aires, placing there the beginning of a process of academic development of psychology which has a historical continuity that crown with the implantation of the experimental psychology by Horacio Piñero in 1902. We understand that the latter found an academic and institutional context that allows and even demands its reception, and that such conditions of registration will begin with the teaching in law by Weigel Muñoz. We believe that this course is not a mere antecedent, but already has a degree of structure that includes the main lines of current psychological thinking and institutes a discursive dimension which will be built on the continuity of psychological thought once the Faculty of Philosophy and Letters is created.