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Increased levels of soluble forms of adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1) and E-selectin have been found in the sera of HIV-infected patients and have been associated with disease progression. The aim of the present study was to investigate whether this phenomenon reflects activation of the non-adaptive immune response in HIV infection. Fifty-one patients with HIV infection (42 men, nine women) were classified into two subgroups: those with HIV infection but without evidence of AIDS indicator conditions (HIV infected non-AIDS cases, n = 27) and those with AIDS (AIDS cases, n = 24). The activation of non-adaptive immune response was evaluated as the production of reactive oxygen species that cause lipid peroxidation, which was assessed by measuring thiobarbituric reactive substances (TBARS) using the thiobarbituric acid assay (TBA). Plasma levels of von Willebrand factor (vWF), measured by rocket immunoelectrophoresis, were used to show activation of endothelial cells even in the absence of any other causative agent, in these patients. TBARS levels in non-AIDS cases were significantly higher than in control subjects (n = 17) or AIDS cases (P < 0.001). The mean vWF levels were higher in AIDS cases than in non-AIDS cases or normal subjects (P < 0.05). TBARS levels remained significantly higher in non-AIDS cases after adjusting for age, CD4 T-cell and neutrophil counts, antiretroviral therapy and vWF plasma levels. The above findings indicate that in HIV infection, the virus per se is responsible for the increased oxidative stress that in turn activates various transduction pathways, may be leading to endothelial cell activation and shedding of adhesion molecules from the cell surface. Eur J Clin Invest more...

To identify individuals with antinuclear antibodies (ANA) not fulfilling criteria for systemic lupus erythematosus (SLE) or other connective tissue diseases (CTD); to describe their clinical and serological features, to identify factors indicating evolution to SLE.A case-control study, based on retrospective evaluation of clinical files. The cases were ANA positive individuals (n = 50) examined in a medical outpatient setting, for symptoms compatible with SLE, but not fulfilling SLE classification criteria. Two patients with SLE were matched to each case in terms of age at initial symptom onset and sex. Thyroid autoimmunity was assessed by detecting antithyroid antibodies. Fisher's exact test and conditional logistic regression were used to evaluate the predictive ability of initial findings for SLE development.ANA positive individuals suspected of having a CTD present a wide variety of symptoms and findings, usually at the 4th to 5th decade of life. Antibodies to Sm and U1RNP were absent; anti-Ro(SSA) and anti-La(SSB) occurred in 6%, while anti-dsDNA occurred in less than 10% of the cases. Arthritis, butterfly and discoid rash, Raynaud's phenomenon, and anti-Ro/SSA antibodies are the initial findings indicating evolution to SLE. Hematological abnormalities such as leukopenia and thrombocytopenia as well as constitutional symptoms such as easy fatigue and arthralgias are not associated with evolution to SLE. Antithyroid antibodies were detected in 16% of the cases and 2.3% of controls.ANA may connote a form of systemic autoimmunity that is expressed as a wide variety of complaints, even in the absence of a definite diagnosis of CTD. Arthritis, rash, Raynaud's phenomenon, and anti-Ro/SSA antibodies indicate evolution to SLE. Autoimmune thyroid disease occurs in ANA positive individuals not fulfilling SLE classification criteria rather than in patients with SLE. more...

Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1α/β inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR ≥6 ng ml−1, 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26–0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P, The SAVE-MORE phase 3 study demonstrates the efficacy of anakinra, an IL-1α/β inhibitor, in patients with COVID-19 and high serum levels of soluble plasminogen activator receptor. more...