Ultrasound evaluation of carotid intima-media thickness (cIMT) has been extensively used for potentially improving cardiovascular (CV) risk stratification in several patients' categories. Subjects with systemic lupus erythematosus (SLE) have been investigated by both imaging and molecular biomarker approaches with contrasting results. Here, we focused on the role of osteopontin (OPN) as biomarker of subclinical atherosclerosis associated with SLE.Eighty females (age 18-65 years) affected by SLE and eighty age-matched healthy female controls without a clinical history of CV disease underwent ultrasound evaluation of cIMT and blood sample assay of high-sensitivity C-reactive protein (hs-CRP) and OPN.Healthy controls and SLE patients significantly differed for CV risk factors (ie, waist circumference, hypertension and dyslipidaemia) and the inflammatory status. Noteworthy, an opposite association between cIMT and OPN was observed in the two study groups. Whereas OPN was positively associated with mean cIMT (r = 0.364; P = 0.001) in SLE patients, a negative correlation was found in healthy controls. Furthermore, in SLE patients increased circulating levels of OPN were associated with the use of hydroxychloroquine and the positivity for the anti-dsDNA autoantibodies. At linear regression analysis, only OPN remained independently associated with cIMT also after adjustment for age, smoking pack-year, Heart SCORE, disease length and steroid therapy length.These results indicate that serum OPN levels were strongly associated with subclinical atherosclerosis in patients with LES and it might be a useful CV biomarker that requires additional validation in larger trials.
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-kB 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-kB 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.
Allergic rhinitis (AR) is characterized by a Th2 polarized immune response. Specific Immunotherapy modifies this bias restoring a physiologic Th1 profile. Sublingual immunotherapy (SLIT) is widely prescribed, but there is no early, simple marker of response. This study was undertaken in order to determine whether serum IL-4 might be a possible marker of SLIT immunological response in order to quickly and easily detect responder patients. Thirty-nine AR patients with a pollen allergy assumed preseasonal SLIT for 3 months. VAS for symptoms and medication efficacy were evaluated. Serum IL-4 was assessed before and 3 and 6 months after SLIT initiation. Eighty-two percent of patients (32/39) showed a clinical response to SLIT. Serum IL-4 significantly decreased at 6 months post-therapy in responders, whereas it increased in non-responders. In conclusion, these results may be considered clinically relevant proof that SLIT treatment induces a quick reduction in Th2 polarization. Serum IL-4 appears to be an early marker of immunological response to SLIT.
Ongoing progress in understanding the pathogenic mechanisms regulating various immune-mediated and inflammatory diseases, as well as the availability of innovative biotechnological approaches, have lead to the development of new drugs that add to conventional treatments. Among these, tumor necrosis factor (TNF)-α inhibitors such as infliximab, adalimumab, etanercept, golimumab and certolizumab pegol, are now available for clinical use. Adalimumab is a fully recombinant human immunoglobulin G1 monoclonal antibody that specifically binds with high affinity to human TNF-α and inhibits its binding to TNF receptors. Adalimumab was approved by the U.S. FDA in 2002 and was granted approval from the European Medicines Agency in September 2003 for the treatment of moderate to severe rheumatoid arthritis and subsequently for the treatment of ankylosing spondylitis, chronic plaque psoriasis, psoriatic arthritis, juvenile idiopathic arthritis and Crohn's disease. In this paper, we will briefly review the structure and biological effects of TNF-α, the old and recent indications of adalimumab, the pretreatment considerations, the reported adverse events and finally, the recommendations for its use in pregnancy.
