BAFF/APRIL pathway in Sjögren syndrome and systemic lupus erythematosus: relationship with chronic inflammation and disease activity

Objectives: BAFF and APRIL belong to the tumor necrosis factor (TNF) superfamily and are crucial for the survival, maturation, and differentiation of B cells. Aim of the study is to evaluate BAFF and APRIL in patients affected by Sjögren syndrome (SS) and systemic lupus erythematosus (SLE). Methods: Sixty patients, (40 SLE, 20 SS) and 20 healthy subjects were enrolled in this study. All subjects were evaluated for laboratory data (ESR, CRP, immunoglobulin G, A and M, complement fragments C3 and C4, LDH, beta2microglobulin, serum levels of rheumatoid factor), autoantibodies (ANA; ENA-SSA, -SSB, -Sm) and lymphocytes subpopulations. For patients, disease activity and damage indexes were assessed with the use of SLEDAI and SLICC and SSDAI and SSDDI for SLE and SS, respectively. BAFF and APRIL were determined by commercial sandwich ELISA kit (R&D Systems, Bender MedSystem). Statistical analysis has been performed with software Prism (Graphpad Instat, version 5.00). Results: APRIL levels were higher among SLE and SS patients compared to controls (p<0.0001, and p0.0001, respectively). BAFF levels in SLE were significantly higher than in SS (p<0.0001). We found higher BAFF levels in SLE and SS compared to controls (p<0.0001). Among SLE patients APRIL correlated with SLEDAI (r 0.3, p 0.04), SLICC (r 0.5,p 0.001), ESR (r 0.3, p 0.005) and CRP (r 0.4, p 0.02). Among SS patients APRIL correlated with SSDAI (r 0.4, p 0.02), SSDDI (r 0.4, p0.01), IgG (r 0.5, p0.01), ESR (r 0.6, p 0.01), CRP (r 0.6, p 0.02) and CD19 B lymphocytes absolute count (r 0.4, p 0.04); BAFF correlated with SSDDI (r 0.7, p 0.004) and CD19 B lymphocytes absolute count (r 0.5, p 0.04). Conclusions: In this study we showed a correlation between disease activity, damage indexes and BAFF/APRIL levels in SLE and SS patients suggesting a role in the strong activation of the immune system in patients with active disease

Neuropsychiatric Lupus Erythematosus

Neuropsychiatric involvement in patients with Systemic Lupus Erythematosus (SLE), first mentioned by Kaposi more than 100 years ago, still remains one of the main challenge facing rheumatologist and other physicians. The diagnosis of neuropsychiatric SLE (NPSLE) is complex not only because of the considerable prevalence variation (14-80%) but also because of the wide spectrum of NP manifestations. They vary from overt neurologic alterations (seizure, psychosis), to subtle abnormalities (neurocognitive dysfunctions). Different NP manifestations result from a variety of mechanisms including antibodies, vasculitis, thrombosis, hemorrhages and cytokine-mediated damages. Of note, despite the dramatic clinical manifestations, too often changes at the morphological neuroimaging techniques are minimal and non specific. There is no one diagnostic tool specific for NPSLE and diagnosis must be based on the combinated use of immunoserological tests, functional and anatomical neuroimaging and standardized specific criteria. Symptomatic, immunosuppressive and anticoagulant therapies are the main strategies available in the management of these patients. Therapy for CNS lupus should be adjusted according to the needs of the individual patients. The coming years promise to be an important time for the development of new neuroimaging techniques and for the study of disease mechanism. An early and objective identification of brain involvement will allow for appropriate treatment to avoid severe complications

Alexithymia and immunoendocrine parameters in patients affected by systemic lupus erythematosus and rheumatoid arthritis

Objective: Aim of this study was to evaluate the prevalence of alexithymia in patients affected by SLE or RA and to investigate the correlation between alexithymia and immunoendocrine parameters (PRL, hGH, IL-6 and TNF-alfa). Methods: Twenty-five patients (12 and 13 affected by SLE and RA, respectively) were enrolled into the study. The Toronto Alexithymia Scale-20 (TAS-20) was administered. PRL, hGH, IL-6 and TNF-alfa levels were measured by commercially available ELISA kits. Results: Alexithymia prevalence (TAS-20≥51) was 54% in RA and 42% in SLE patients. hGH serum levels were 3.1±4.2 and 1.1±0.9 IU/ml in SLE and RA, respectively. PRL concentration was 18.4±6.5 ng/ml and 14.2±4.0 ng/ml in SLE and RA patients, respectively (p=0.03). In RA group, TNF-alpha was 20±36.2 whereas in SLE it was 4.9±12.8 pg/ml (p=0.03); IL-6 serum concentrations were 24.4±25.1 and 2.9±5.4 pg/ml, in RA and SLE respectively (p=0.004). The serum level of hGH showed slight increase in alexithymic group (A) compared to non alexithymic group (NA) in both SLE and RA patients. PRL serum levels in SLE-A patients was 26.7±17.3 ng/ml while in SLE-NA patients was 12.4±3.3 ng/ml (p=0.04). In RA patients increased values of IL-6 and TNF-alpha were present in the A group compared to NA group (IL-6: 35.3±28 pg/mL vs 3.5±3.9 pg/mL, p=0.01; TNF-alpha: 34.7±39 pg/mL vs 3.1±3.4 pg/mL, p=0.01). Conclusions: In this preliminary results we found an high prevalence of alexithymia and a correlation between immunoendocrine parameters and alexhytimic features in SLE and RA, suggesting that an immunomodulatory pathway could influence this cognitive style in patients with autoimmune disorders. Other studies should contribute to find a common biological pathway linking alexithymia and autoimmunity

Gender equality in Rheumatology.

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Impaired immunogenicity to COVID-19 vaccines in autoimmune systemic diseases. High prevalence of non-response in different patients’ subgroups

Autoimmune systemic diseases (ASD) may show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed to evaluate the seroconversion after the vaccination cycle and at 6-12-month follow-up, as well the safety and efficacy of vaccines in preventing COVID-19. The study included 478 unselected ASD patients (mean age 59 ± 15 years), namely 101 rheumatoid arthritis (RA), 38 systemic lupus erythematosus (SLE), 265 systemic sclerosis (SSc), 61 cryoglobulinemic vasculitis (CV), and a miscellanea of 13 systemic vasculitis. The control group included 502 individuals from the general population (mean age 59 ± 14SD years). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was evaluated by measuring serum IgG-neutralizing antibody (NAb) (SARS-CoV-2 IgG II Quant antibody test kit; Abbott Laboratories, Chicago, IL) on samples obtained within 3 weeks after vaccination cycle. The short-term results of our prospective study revealed significantly lower NAb levels in ASD series compared to controls [286 (53–1203) vs 825 (451–1542) BAU/mL, p &lt; 0.0001], as well as between single ASD subgroups and controls. More interestingly, higher percentage of non-responders to vaccine was recorded in ASD patients compared to controls [13.2% (63/478), vs 2.8% (14/502); p &lt; 0.0001]. Increased prevalence of non-response to vaccine was also observed in different ASD subgroups, in patients with ASD-related interstitial lung disease (p = 0.009), and in those treated with glucocorticoids (p = 0.002), mycophenolate-mofetil (p &lt; 0.0001), or rituximab (p &lt; 0.0001). Comparable percentages of vaccine-related adverse effects were recorded among responder and non-responder ASD patients. Patients with weak/absent seroconversion, believed to be immune to SARS-CoV-2 infection, are at high risk to develop COVID-19. Early determination of serum NAb after vaccination cycle may allow to identify three main groups of ASD patients: responders, subjects with suboptimal response, non-responders. Patients with suboptimal response should be prioritized for a booster-dose of vaccine, while a different type of vaccine could be administered to non-responder individuals

ps4 79 long term follow up of 320 chilren born to mothers with systemic autoimmune diseases a multicentre survey from 24 rheumatology centres in italy

Background Rheumatic Diseases (RD) frequently affect women during reproductive age, therefore counselling on family planning is crucial for their quality of life. Children's outcome is a major topic, but no large studies are available. This study aimed at assessing the long-term health conditions of children born to women with RD. Methods 24 Italian Rheumatology Centres distributed the questionnaire (65 multiple-choice and 12 open-answer questions) to consecutive patients (aged 18–55) during September 2015. Data were analysed dividing children upon maternal diagnosis: Chronic Arthritides (CA) and Connective Tissue Diseases (CTD). Results Data were collected for 320 children born to 184 mothers (63 CA and 121 CTD). At the time of interview, children had a mean age of 17.1±9.6 years. Pre-term delivery ( The occurrence of an autoimmune/inflammatory disease (AIID) and/or neurodevelopmental disorders (ND)/learning disabilities (LD) is reported in table 1. Twelve children (3.7%) were diagnosed with an AIID, mostly coeliac disease (8/12, 67%). Eleven children (3.4%) were diagnosed as having a ND and/or LD by a Paediatric Neuropsychiatrist. Data of in utero exposure to maternal autoantibodies and/or anti-rheumatic drugs were retrieved for 280 children (87.5%) and a comparison was performed between affected (n=11) and not-affected children (n=258). No association was found with ND/LD and in utero exposure to autoantibodies (ANA, anti-Ro, anti-dsDNA, aPL) or drugs (HCQ,AZA or steroids), neither with sex, preterm birth, birth weight or maternal diagnosis. Conclusions The long-term follow-up of children born to mothers with RD did not raise particular concerns in terms of relevant health problems. In particular, each AIID did not display a significantly increased frequency as compared to the literature. Children with ND/LD had a tendency to cluster in the group of mothers with CTD, especially after maternal diagnosis, with a higher frequency as compared to GPP (7.9% vs 3%). Our data suggest that the development of ND/LD in children of patients with RD cannot be linked exclusively to maternal disease. The results of this study can be reassuring for patients with RD about problems in the offspring possibly related to their disease