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Systemic lupus erythematosus (SLE) is characterized by the production of a wide array of autoantibodies and dysregulation of B cell function. The leukocyte associated Immunoglobulin (Ig)-like receptor (LAIR)1 is a transmembrane molecule belonging to Ig superfamily which binds to different types of collagen. Herein, we have determined the expression and function of LAIR1 on B lymphocyte from SLE patients. LAIR1 expression in peripheral blood B lymphocytes from 54 SLE, 24 mixed connective tissue disease (MCTD), 20 systemic sclerosis (SSc) patients, 14 rheumatoid arthritis (RA) and 40 sex and age matched healthy donors (HD) have been analyzed by immunofluorescence. The effect of LAIR1 ligation by specific monoclonal antibodies, collagen or collagen producing mesenchymal stromal cells from reactive lymph nodes or bone marrow on Ig production by pokeweed mitogen and B cell receptor (BCR)-mediated NF-κB activation was assessed by ELISA and TransAM assay. The percentage of CD20+ B lymphocytes lacking or showing reduced expression of LAIR1 was markedly increased in SLE and MCTD but not in SSc or RA patients compared to HD. The downregulation of LAIR1 expression was not dependent on corticosteroid therapy. Interestingly, LAIR1 engagement by collagen or collagen-producing mesenchymal stromal cells in SLE patients with low LAIR1 expression on B cells delivered a lower inhibiting signal on Ig production. In addition, NF-κB p65 subunit activation upon BCR and LAIR1 co-engagement was less inhibited in SLE patients than in HD. Our findings indicate defective LAIR1 expression and function in SLE B lymphocytes, possible contributing to an altered control of B lymphocytes behavior. [ABSTRACT FROM AUTHOR]

Accelerated atherosclerosis is an emerging problem in patients with systemic lupus erythematosus (SLE). We planned an observational study to determine whether in patients with SLE carotid intima-media thickness (IMT) represents an early sign of accelerated atherosclerosis and to confirm that SLE adds to the traditional cardiovascular Framingham risk factors. Thirty females with SLE (age 18–65 years) underwent anamnestic, clinical, and laboratory evaluation and B-mode ultrasonography of carotid arteries, which provides a direct and noninvasive assessment of subclinical atherosclerosis. IMT measurements were performed on the right and left common carotid arteries 1.0 cm proximal to the carotid bulb and the mean IMT value was calculated with a dedicated software. The Framingham Point Score was also calculated for each subject. SLE patients showed a mean IMT value of 0.73 ± 0.12 (SD) mm. This value is significantly ( P < 0.05) higher than that reported for an age-matched healthy female control population (0.66 ± 0.11 SD mm). A preliminary evaluation of the Framingham Point Score, estimating the 10-year risk for women to develop cardiovascular events, indicated an increased risk of early cardiovascular events in SLE patients. In our study we have shown that patients with SLE have an increased mean IMT value compared with a healthy females control. Moreover, the evaluation of the Framingham Point Score suggests that SLE is an additional risk factor for cardiovascular disease. [ABSTRACT FROM AUTHOR]

Several allergic and immunologic diseases including asthma, food allergy (FA), chronic spontaneous urticaria (CSU), atopic dermatitis (AD), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), and Behçet's disease (BD) are characterized by the involvement of Th2 immunity. Several mediators lead to immunoglobulin (Ig)E production, thus including key cytokines such as interleukin (IL)-4, IL-5, and IL-13. Among them, IL-31 and IL-33 have been recently studied as novel biomarkers and future therapeutic targets for allergic and immunological disorders. IL-31 is a proinflammatory cytokine—it regulates cell proliferation and is involved in tissue remodeling. IL-33, acting through its receptor suppression of tumorigenity (ST2L), is an alarmin cytokine from the IL-1 family, whose expression is mediated by tissue damage. The latter has a pleiotropic effect, as it may modulate specific and innate immune cells functions. To date, several researchers have investigated the involvement of IL-31 and IL-33 in several allergic and immune-mediated diseases. Further studies are needed to understand the future applications of these molecules as novel therapeutic agents. This paper aims to give the readers a complete and updated review of IL-31 and IL-33 involvement among the most common autoimmune and allergic disorders. [ABSTRACT FROM AUTHOR]

Abstract: B-cells abnormalities leading to autoantibody production play a central role in Systemic Lupus Erythematosus (SLE) pathogenesis. B-cell targeted therapies, including anti-B lymphocyte stimulator (BLyS) and anti-CD20 monoclonal antibodies, are at forefront of new SLE treatments. Biologic agents targeting specific pathways (i.e. T-B lymphocyte interaction, cytokines and complement) have been also proposed as new tools for SLE treatment. In this review we will focus on biological drugs whose potential efficacy has been evaluated in open-label and randomized clinical trials. [Copyright &y& Elsevier]

Human leucocyte antigen-G (HLA-G) is a nonclassical class I major histocompatibility complex (MHC) molecule characterized by complex immunoregulatory and tolerogenic functions. Membrane-bound HLA-G is expressed on the surface of different cell populations in both physiological and pathological conditions. Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by widespread tissue fibrosis, vascular lesions and immunological alterations. Systemic lupus erythematosus is the prototypic systemic autoimmune disease affecting virtually any organ system, such as skin, joints, central nervous system, or kidneys. In SSc and SLE patients, the membrane expression of HLA-G on monocytes (0.88 ± 1.54 and 0.43 ± 0.75, respectively), CD4+ (0.42 ± 0.78 and 0.63 ± 0.48, respectively), CD8+ (2.65 ± 3.47 and 1.29 ± 1.34, respectively) and CD4+ CD8+ double-positive cells (13.87 ± 15.97 and 3.79 ± 3.11, respectively) was significantly higher than in healthy controls (0.12 ± 0.07; 0.01 ± 0.01; 0.14 ± 0.20 and 0.32 ± 0.38, respectively) (p < 0.0001). Our results show that in SSc and SLE the membrane expression of HLA-G by different subpopulations of peripheral blood mononuclear cells (PBMC) is increased, suggesting a potential role of HLA-G molecules in the complex immunological pathogenesis of these two autoimmune disorders. [ABSTRACT FROM AUTHOR]

Research on autoimmune processes involved in glomerulonephritis has been for years based on experimental models. Recent progress in proteomics has radically modified perspectives: laser microdissection and proteomics were crucial for an in vivo analysis of autoantibodies eluted from human biopsies. Lupus nephritis has been the subject of recent independent researches. Main topics have been the definition of renal autoimmune components in human lupus biopsies; methods were laser capture of glomeruli and/or of single cells (CD38 + or Ki-67 +) from tubulointerstitial areas as starting step followed by elution and characterization of renal antibodies by proteomics. The innovative approach highlighted different panels of autoantibodies deposited in glomeruli and in tubulo-interstitial areas that actually represented the unique autoimmune components in these patients. IgG2 was the major isotype; new podocyte proteins (αenolase, annexin AI) and already known implanted molecules (DNA, histone 3, C1q) were their target antigens in glomeruli. Vimentin was the antigen in tubulo-interstitial areas. Matching renal autoantibodies with serum allowed the definition of a typical autoantibody serum map that included the same anti-αenolase, anti-annexin AI, anti-DNA, and anti-histone 3 IgG2 already detected in renal tissue. Serum levels of specific autoantibodies were tenfold increased in patients with lupus nephritis allowing a clear differentiation from both rheumatoid arthritis and other glomerulonephritis. In all cases, targeted antigens were characterized as components of lupus NETosis. Matching renal/serum autoantibody composition in vivo furnishes new insights on human lupus nephritis and allows to refine composition of circulating antibodies in patients with lupus. A thoughtful passage from bench to bedside of new knowledge would expand our clinical and therapeutic opportunities. [ABSTRACT FROM AUTHOR]

Abstract: Systemic lupus erythematosus (SLE) is a chronic immune-mediated inflammatory multisystem disease. The onset of viral and bacterial infections may favor the exacerbation of the disease, amplify autoimmune processes and contribute to mortality and morbidity. The prevention of influenza and Streptococcus pneumoniae infections with vaccination should receive particular attention in SLE patients considering their elevated incidence, their high attack rate in epidemic periods, their potentially severe complications as well as the immunocompromised state of the host. The use of non-adjuvanted vaccine preparations should be preferred in order to avoid the onset of the “Autoimmune (auto-inflammatory) Syndrome Induced by Adjuvants” or “ASIA”. In this review, we report that influenza and pneumococcal vaccinations in SLE patients are: 1) recommended to reduce the risk of development of these infections; 2) strongly suggested in elderly subjects and in those receiving high dose immunosuppressive treatments; 3) efficacious, even if specific immune responses may be lower than in the general population, as generally the humoral response fulfills the criteria for vaccine immunogenicity; and 4) safe in inactive disease although may favor a transient increase in autoantibody levels and rarely disease flares. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate the role of vascular endothelial growth factor (VEGF) in accelerated atherosclerosis in patients with Systemic Lupus Erythematosus (SLE). Methods: We have enrolled 80 SLE female patients and 80 age-matched healthy control females who underwent a structured interview, physical examination, routine laboratory tests, VEGF plasma level determination and B-mode ultrasonography of carotid arteries to determine carotid intima media thickness (IMT). Framingham risk factors for cardiovascular events were also calculated and VEGF plasma levels were correlated with traditional and nontraditional cardiovascular risk factors. Results: SLE was significantly associated with higher mean IMT values (0.74±0.15 mm versus 0.59±0.12 mm in controls, p <0.001) and higher mean plasma VEGF levels (307.9±292.2 pg/mL versus 120.7±118.4 pg/mL in controls, p <0.001) independently from age, smoking habits, and Framingham risk factors. A significant correlation was also found between IMT and VEGF values (r =0.25; p <0.001). Conclusion: We show that SLE patients have increased mean IMT and VEGF values as compared with healthy age-matched controls and that IMT and VEGF values are independently and directly associated with SLE disease. [Copyright &y& Elsevier]