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This study examined the association between dynamic angiopoietin-2 assessment and COVID-19 short- and long-term clinical course. We included consecutive hospitalized patients from 1 February to 31 May 2020 with laboratory-confirmed COVID-19 from 2 Italian tertiary referral centers (derivation cohort, n = 187 patients; validation cohort, n = 62 patients). Serum biomarker levels were measured by sandwich enzyme-linked immunosorbent assay. Lung tissue from 9 patients was stained for angiopoietin-2, Tie2, CD68, and CD34. Cox model was used to identify risk factors for mortality and nonresolving pulmonary condition. Area under the receiver operating characteristic curve (AUROC) was used to assess the accuracy of 3- and 10-day angiopoietin-2 for in-hospital mortality and nonresolving pulmonary condition, respectively. Three-day angiopoietin-2 increase of at least twofold from baseline was significantly associated with in-hospital mortality by multivariate analysis (hazard ratio [HR], 6.69; 95% confidence interval [CI], 1.85-24.19; P = .004) with AUROC = 0.845 (95% CI, 0.725-0.940). Ten-day angiopoietin-2 of at least twofold from baseline was instead significantly associated with nonresolving pulmonary condition by multivariate analysis (HR, 5.33; 95% CI, 1.34-11.77; P ≤ .0001) with AUROC = 0.969 (95% CI, 0.919-1.000). Patients with persistent elevation of 10-day angiopoietin-2 levels showed severe reticular interstitial thickening and fibrous changes on follow-up computed tomography scans. Angiopoietin-2 and Tie2 were diffusely colocalized in small-vessel endothelia and alveolar new vessels and macrophages. Angiopoietin-2 course is strongly associated with COVID-19 in-hospital mortality and nonresolving pulmonary condition. Angiopoietin-2 may be an early and useful predictor of COVID-19 clinical course, and it could be a relevant part of disease pathogenesis. Angiopoietin-2 blockade may be a COVID-19 treatment option.

The methods for detecting and measuring autoantibodies have evolved markedly in recent years, encompassing three generations of analytical technologies. Many different immunoassay methods have been developed and used for research and laboratory practice purposes, from the early conventional (or monoplex) analytical methods able to detect single autoantibodies to the more recent multiplex platforms that can quantify tens of molecules. Although it has been in use for over 50 years, indirect immunofluorescence remains the standard method for research on many types of autoantibodies, due to its characteristics of diagnostic sensitivity and also to recent technological innovations which permit it a greater level of automation and standardization. The recent multiplex immunometric methods, with varying levels of automation, present characteristics of higher diagnostic accuracy, but are not yet widely diffused in autoimmunology laboratories due to the limited number of autoantibodies that are detectable, and due to the high cost of reagents and systems. Technological advancement in autoimmunology continues to evolve rapidly, and in the coming years new proteomic techniques will be able to radically change the approach to diagnostics and possibly also clinical treatment of autoimmune diseases. The scope of this review is to update the state of the art of technologies and methods for the measurement of autoantibodies, with special reference to innovations in indirect immunofluorescence and in multiple proteomic methods.

This study was aimed to analyse the prevalence of antinuclear antibodies in patients with psoriasis after treatment with infliximab and correlates the development of antibodies with both response to treatment and adipokines levels. Serum levels of ANA, anti-dsDNA, anti-histone, anti-nucleosome and anti-ENA antibodies at baseline after 2 and 12 months of treatment with infliximab were measured in 27 patients with psoriasis, as well as in 27 matched controls. Serum C-reactive protein (CRP), chemerin, visfatin and resistin were also assessed. The prevalence of ANA increased from 22 to 37% and 63% (p < 0.01) during treatment with infliximab, with a gradual progressive increase both in ANA titre and in percentage of ANA pattern. The prevalence of other antibodies also increased from 7 to 30% and 48% (p < 0.01) for anti-ds-DNA and from 7 to 26% and 37% for anti-nucleosome antibodies (p < 0.05), whereas the prevalence of anti-histone and anti-ENA antibodies was unchanged throughout the study period. Basal chemerin, resistin and CRP levels were higher in patients than in controls, and their levels progressively normalized during treatment (p < 0.01). Conversely, visfatin levels gradually increased (p < 0.01). ANA+ patients tended to show a faster decrease in PASI score, CRP and chemerin levels after 2 months, but the PASI score did not differ between ANA+ and ANA- patients at 12 months. A higher increase of visfatin was also found in ANA+ patients at 2 and 12 months. The antinuclear antibody response induced by infliximab was restricted to ANA, anti-dsDNA and anti-nucleosome antibodies. Patients who developed ANA positivity showed a faster clinical, inflammatory and immunological response to infliximab therapy.

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