BACKGROUND:Legionella pneumophila is a leading cause of Legionnaires' disease, with Legionella pneumophila serogroup 1 (Lp1) being the most commonly detected strain. Current urinary antigen tests (UAT) primarily target Lp1, leading to underdiagnosis of non-Lp1 and other Legionella species. A broad-spectrum, fully automated UAT is needed to improve diagnostic accuracy and patient outcomes. METHODS:A novel chemiluminescence immunoassay-based UAT was developed targeting both Legionella peptidoglycan-associated lipoprotein (PAL) and soluble lipopolysaccharide antigen to enable broader detection. Monoclonal antibodies were generated against PAL and integrated into an automated immunoassay platform. The assay's analytical performance was evaluated using recombinant PAL antigens, urine samples spiked with Legionella strains, and clinical specimens. Sensitivity, specificity, cross-reactivity, interference, and precision were assessed. RESULTS:The LIAISON® Legionella Urinary Ag assay demonstrated a 97.5 % positive agreement and 100 % negative agreement with the Binax™ UAT in detecting Legionella infections. Importantly, the new test also identified multiple non-Lp1 Legionella species, which the comparator assay failed to detect. The assay showed low imprecision, no cross-reactivity or interference. CONCLUSIONS:The LIAISON® Legionella Urinary Ag Assay, a fully automated chemiluminescence-based UAT, provides highly sensitive and specific detection of Legionella infections, including non-Lp1 strains, addressing a major limitation of existing diagnostics. This assay has the potential to improve early detection, guide targeted antibiotic therapy, and enhance public health surveillance of Legionnaires' disease.

Colorectal cancer (CRC) represents a relevant public health problem, with high incidence and mortality in Western countries. CRC can occur as sporadic (65%-75%), common familial (25%), or as a consequence of an inherited predisposition (up to 10%). While unravelling its genetic basis has been a long trip leading to relevant clinical implementation over more than 30 years, other contributing factors remain to be clarified. Among these, micro-organisms have emerged as critical players in the development and progression of the disease, as well as for CRC treatment response. Fusobacterium nucleatum (Fn) has been associated with CRC development in both pre-clinical models and clinical settings. Fusobacteria are core members of the human oral microbiome, while being less prevalent in the healthy gut, prompting questions about their localization in CRC and its precursor lesions. This review aims to critically discuss the evidence connecting Fn with CRC pathogenesis, its molecular subtypes and clinical outcomes.

Abstract Background There is a need for sensitive clinical diagnostics for early and acute infection as current serology-based tests have low sensitivities in the early phases of the disease and cannot discriminate between acute and past infections. In 2016, using a 33 peptide T-cell stimulating cocktail (QIAGEN prototype), Callister et al. provided the first published evidence showing that the integration of humoral and cell mediated immunity can result in earlier detection of Lyme Disease. Additional data have since shown that interferon γ (IFNγ) release is a marker of acute disease and decreases following antibiotic treatment of the patients. Methods A fully automated chemiluminescence immunoassay was developed that allows the detection of IgG, IgM, and an IFNγ release assay component (QFL) using a proprietary peptide-based technology; an algorithm combines the 3 results into a POS, NEG or IND call. The performance of the assay was compared to standard two-tiered testing (sTTT) in a prospective clinical trial (NCT05041595). Results In 2021, 54 patients with sign and symptoms consistent with Lyme disease were evaluated, as well as 200 healthy subjects from an area of low Lyme incidence. The assay showed significant sensitivity improvement over sTTT (79.6% vs 57.4%). However, suboptimal specificity was observed (89.5%) with some relatively high IFNγ values that required reassessment of the test. A troubleshooting process identified two decorin binding protein peptides as being responsible for most of the non-specific reactivity of QFL. The performance of an updated assay version with a 31-peptide QFL stimulation tube was evaluated in 2022 on 56 patients with erythema migrans, and 99 apparently healthy subjects from endemic areas. Sensitivity and specificity were assessed and compared to sTTT and found to be 73.2% vs 58.9%, and 100% for both, respectively. Conclusion The data presented support the operational utility of the assay as an aid in the diagnosis of early Lyme disease, while providing high specificity after the optimization of the stimulation peptides of the QFL assay component. A promising expanded clinical validation study for the assay is in process for submission to the U.S. Food and Drug Administration. Disclosures Fabrizio Bonelli, PhD, Diasorin SpA: employee Ashli Rode, MS, Diasorin Inc: employee Claudia Zierold, PhD, Diasorin SpA: Advisor/Consultant Jenny Howard, PhD, QIAGEN: Employee|QIAGEN: Stocks/Bonds (Public Company) Nadia Allen, PhD, QIAGEN: employee|QIAGEN: Stocks/Bonds (Public Company) Giorgio Ghignoni, MD, Diasorin: Employee

The clinical diagnosis, severity assessment, and outcome prognostication of community-acquired pneumonia (CAP) remain challenging due to the complex disease pathophysiology. Accurate outcome prediction is crucial for optimizing patient management, reducing mortality, and minimizing hospital and ICU admissions. In this prospective observational cohort study, 228 CAP patients with varying degrees of disease severity were assessed. Clinical and demographic data, along with multiple biomarker measurements, including pentraxin-3 (PTX3), were analysed longitudinally. The primary outcome was clinical failure. Among the single parameters evaluated, the oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2), PTX3, and mid-regional pro-adrenomedullin (MRproADM) demonstrated the strongest predictive performance, with areas under the curve (AUC) of 0.799, 0.709, and 0.647, respectively. Machine learning (ML) experiments integrating multiple features identified the optimal algorithm for outcome prediction, combining these stand-alone markers at baseline and 72 h. The optimal ML model achieved an AUC of 0.950 (95

This record contains raw data related to article “mRNA COVID-19 vaccine booster fosters B- and T-cell responses in immunocompromised patients" SARS-CoV-2 vaccination has proven effective in inducing an immune response in healthy individuals and is progressively us allowing to overcome the pandemic. Recent evidence has shown that response to vaccination in some vulnerable patients may be diminished, and it has been proposed a booster dose. We tested the kinetic of development of serum antibodies to the SARS-CoV-2 Spike protein, their neutralizing capacity, the CD4 and CD8 IFN-γ T-cell response in 328 subjects, including 131 immunocompromised individuals (cancer, rheumatologic, and hemodialysis patients), 160 health-care workers (HCW) and 37 subjects older than 75 yr, after vaccination with two or three doses of mRNA vaccines. We stratified the patients according to the type of treatment. We found that immunocompromised patients, depending on the type of treatment, poorly respond to SARS-CoV-2 mRNA vaccines. However, an additional booster dose of vaccine induced a good immune response in almost all of the patients except those receiving anti-CD20 antibody. Similarly to HCW, previously infected and vaccinated immunocompromised individuals demonstrate a stronger SARS-CoV-2-specific immune response than those who are vaccinated without prior infection.

SARS-CoV-2 vaccination has proven effective in inducing an immune response towards the Spike protein in healthy individuals and is progressively allowing to overcome the pandemic. Recent evidence has shown that response to vaccination in some vulnerable patients may be diminished, and it has been proposed a booster dose. We tested the kinetic of development of serum antibodies to the trimeric form of the SARS-CoV-2 Spike protein, their neutralizing capacity, the CD4 and CD8 IFN-{gamma} T cell response in 328 subjects, including 131 fragile individuals (cancer, rheumatologic, and hemodialysis patients), 160 healthcare workers (HCW) and 37 subjects older than 75 yo, after vaccination with two or three doses of mRNA vaccines. We stratified the patients according to the type of treatment. We found that fragile patients, depending on the type of treatment, poorly respond to SARS-CoV-2 mRNA vaccines. However, an additional booster dose of vaccine induced a good immune response in almost all of the patients except those receiving anti-CD20 antibody. Similarly to HCW, previously infected and vaccinated fragile individuals demonstrate a stronger SARS-CoV-2 specific immune response than those who are vaccinated without prior infection.

Background Heterogeneous progression of chronic kidney disease (CKD) toward dialysis advocates improving in renal care management. Diagnosis and staging of CKD relies on estimated glomerular filtration rate (eGFR) and albuminuria. Tubular biomarkers emerged as new predictors of worsening renal function (WRF), due to partial inaccuracy of eGFR and existing WRF in non-proteinuric patients. Active vitamin D is synthesized in renal tubules and participates to mineral adaptation in CKD. Circulating 1,25-dihydroxyvitamin D [1,25(OH)2D] was poorly investigated as a biomarker of endocrine tubular function and predictor of WRF. Objective Investigate capability of 1,25(OH)2D to predict parathormone (PTH) increase and WRF in CKD stage 3–4. Methods PASCaL-1,25D was an observational, prospective, monocentric study. Primary outcomes were absolute and 20% increase in PTH, and WRF defined as 20% reduction in eGFR or dialysis initiation at 6 months. Results Seventy-one patients completed follow up. Absolute increase in PTH (1–84) was independently predicted by lower 1,25(OH)2D levels (p = 0.0134). No association was detected between 1,25(OH)2D and iPTH increase. Higher 1,25(OH)2D was associated with reduced risk of WRF at univariate analysis [OR 0.89 (95% CI 0.86–0.93), p = 0.006]. The 1,25(OH)2D/PTH (1–84) ratio was associated with non-significant 84% risk reduction for WRF [OR 0.16 (95% CI 0.06–0.41), p = 0.05]. Low 1,25(OH)2D reached 100% sensitivity in predicting WRF in CKD stage 3 (AUC 9.909, p < 0.0001) and non-elderly patients (AUC 0.883, p < 0.0001). Machine learning models retained 1,25(OH)2D/PTH (1–84) as relevant predictor of WRF together with eGFR and albuminuria. Age influenced interaction between renal and mineral biomarkers. Conclusion 1,25(OH)2D deserves attention as biomarker of tubular health, and sensible predictor of WRF on the short run among non-elderly patients affected by stage 3 CKD. The 1,25(OH)2D/PTH (1–84) ratio may represent a composite biomarker of tubular reserve/endocrine response to the transition from adaptive to maladaptive equilibrium in CKD-MBD.

Immunocompromised patients poorly respond to two doses of SARS-CoV-2 mRNA vaccines. However, an additional booster dose elicits a strong humoral and cellular immune response in these subjects. SARS-CoV-2 vaccination has proven effective in inducing an immune response in healthy individuals and is progressively us allowing to overcome the pandemic. Recent evidence has shown that response to vaccination in some vulnerable patients may be diminished, and it has been proposed a booster dose. We tested the kinetic of development of serum antibodies to the SARS-CoV-2 Spike protein, their neutralizing capacity, the CD4 and CD8 IFN-γ T-cell response in 328 subjects, including 131 immunocompromised individuals (cancer, rheumatologic, and hemodialysis patients), 160 health-care workers (HCW) and 37 subjects older than 75 yr, after vaccination with two or three doses of mRNA vaccines. We stratified the patients according to the type of treatment. We found that immunocompromised patients, depending on the type of treatment, poorly respond to SARS-CoV-2 mRNA vaccines. However, an additional booster dose of vaccine induced a good immune response in almost all of the patients except those receiving anti-CD20 antibody. Similarly to HCW, previously infected and vaccinated immunocompromised individuals demonstrate a stronger SARS-CoV-2–specific immune response than those who are vaccinated without prior infection.

AbstractIntroductionFecal calprotectin (FC) is established as a diagnostic marker to differentiate between inflammatory bowel diseases and non‐inflammatory conditions. Furthermore, it may be effective in monitoring response to treatment, and to predict relapse during maintenance therapy.DesignThis was a prospective longitudinal study carried out in Italy, France and Spain. The primary objective was to correlate the LIAISON® Calprotectin assay measurements to quiescent ulcerative colitis (UC) or relapse as assessed by clinical data. Patients were assessed every 3 months for 12 months, and at 18 months.ResultsThe last FC measured prior to relapse was the variable that predicted relapse in a statistically significant manner. With a 62.3 μg/g cut‐off the area under the curve was 0.619, and the sensitivity was 62.9% (95% Confidence Interval [CI] 44.9%–78.5%) and specificity 63.0% (95% CI 53.1%–72.1%). Using machine learning methods, the last FC measurement was shown to have the largest impact in predicting relapse. An algorithm was developed that included other variables available following a clinician's visit, which resulted in an area under the curve of 0.754 for predicting relapse.ConclusionIn the present study FC measured by the LIAISON® Calprotectin assay on the visit before relapse is predictive of relapse in patients with quiescent UC. In a proof of concept, the accuracy of prediction can further be improved including other variables in an algorithm developed by machine learning.Trial registrationThe trial is registered at clinicaltrials.gov with reference number NCT05168917.

1AdRes Health Economics and Outcomes Research, Torino, Italy; 2DiaSorin SpA, via Crescentino, Saluggia, 13040, Italy; 3Division of Laboratory Medicine, University Hospital Giuliano Isontina (ASU GI), Trieste, Italy Purpose: This Lyme disease early detection economic model, for patients with suspected Lyme disease without erythema migrans (EM), compares outcomes of standard two-tier testing (sTTT), modified two-tier testing (mTTT) and the DiaSorin Lyme Detection Algorithm (LDA), a combination of both serology tests and Interferon-ɤ Release Assay. Patients and Methods: A patient-level simulation model was built to incorporate effectiveness estimation from a structured focused literature review, and health-care cost inputs for the United States, Germany, and Italy. Simulated clinical outcomes were 1) percent of patients with timely and correct diagnosis, 2) patients appropriately treated and exposed to antibiotics therapy, and 3) patients with late Lyme disease manifestations. Expected health outcomes were expressed in terms of differences in quality-adjusted life years (QALYs) due to disseminated Lyme disease and persisting symptoms, and economic outcomes were analyzed from a third-party payer perspective. Results: The DiaSorin LDA resulted in a better sensitivity compared to sTTT and mTTT, 84% vs 49% and 45%, respectively, in the base case (13% of infected patients in the tested population). Due to the improved diagnostic performance, the LDA-based strategy is expected to be more effective, providing mean incremental 0.024 QALYs per tested patient, or 0.19 per infected patient. Furthermore, from a third-party payer perspective, the adoption of the LDA-based strategy would reduce the expected health-care cost for suspected and confirmed Lyme disease by roughly 40%, ie about $410, €130, and €170 per tested patient in the United States, Germany, and Italy, respectively, compared to sTTT. The results are most sensitive to the infection rate in the tested population, with LDA maintaining a cost advantage for Lyme disease active infection rates ≥0.8-2.5%. Conclusion: LDA early diagnostic testing and subsequent treatment of subjects with early Lyme disease without EM are expected to outperform traditional management strategies both clinically and economically in the US, Germany, and Italy.

Purpose This Lyme disease early detection economic model, for patients with suspected Lyme disease without erythema migrans (EM), compares outcomes of standard two-tier testing (sTTT), modified two-tier testing (mTTT) and the DiaSorin Lyme Detection Algorithm (LDA), a combination of both serology tests and Interferon-ɤ Release Assay. Patients and Methods A patient-level simulation model was built to incorporate effectiveness estimation from a structured focused literature review, and health-care cost inputs for the United States, Germany, and Italy. Simulated clinical outcomes were 1) percent of patients with timely and correct diagnosis, 2) patients appropriately treated and exposed to antibiotics therapy, and 3) patients with late Lyme disease manifestations. Expected health outcomes were expressed in terms of differences in quality-adjusted life years (QALYs) due to disseminated Lyme disease and persisting symptoms, and economic outcomes were analyzed from a third-party payer perspective. Results The DiaSorin LDA resulted in a better sensitivity compared to sTTT and mTTT, 84% vs 49% and 45%, respectively, in the base case (13% of infected patients in the tested population). Due to the improved diagnostic performance, the LDA-based strategy is expected to be more effective, providing mean incremental 0.024 QALYs per tested patient, or 0.19 per infected patient. Furthermore, from a third-party payer perspective, the adoption of the LDA-based strategy would reduce the expected health-care cost for suspected and confirmed Lyme disease by roughly 40%, ie about $410, €130, and €170 per tested patient in the United States, Germany, and Italy, respectively, compared to sTTT. The results are most sensitive to the infection rate in the tested population, with LDA maintaining a cost advantage for Lyme disease active infection rates ≥0.8-2.5%. Conclusion LDA early diagnostic testing and subsequent treatment of subjects with early Lyme disease without EM are expected to outperform traditional management strategies both clinically and economically in the US, Germany, and Italy.

Abstract Objectives COVID-19 has brought about tests from many manufacturers. While molecular and rapid antigen tests are targeted for early diagnosis, immunoassays have a larger role in epidemiological studies, understanding longitudinal immunity, and in vaccine development and response. Methods The performance of the LIAISON® SARS-CoV-2 TrimericS IgG assay was evaluated against the Beckman ACCESS SARS-CoV-2 IgG assay in New Mexico, and against the Siemens ADVIA Centaur COV2G assay in New York. Discordant samples were parsed using a microneutralization assay. Results A SARS-CoV-2 antibody positivity rate of 23.8% was observed in the samples tested in New York (September 2020), while in the same month the positivity rate was 1.5% in New Mexico. Positive and negative agreement were 67.6% (95% CI 49.5–82.6%) and 99.8% (95% CI 99.5–99.9%), respectively, with the Beckman test, and 98.0% (95% CI 95.7–99.3%) and 94.8% (95% CI 93.4–96.0%), respectively, with the Siemens test. Receiver operating characteristic analysis for the detection of SARS-CoV-2 antibodies discloses an AUC, area under the curve, of 0.996 (95% CI 0.992–0.999) for the LIAISON® SARS-CoV-2 TrimericS IgG assay. The criterion associated to the Youden Index was determined to be >12.9 kAU/L with a sensitivity of 99.44% and a specificity of 99.82%. Conclusions The LIAISON® SARS-CoV-2 TrimericS IgG assay is highly sensitive and specific. The balance of these parameters, without emphasis on high specificity alone, is particularly important when applied to high prevalence populations, where a highly sensitive assay will result in reporting a lower number of false negative subjects.

In the coronavirus (CoV) disease 2019 (COVID-19) pandemic, highly selective serological testing is essential to define exposure to severe acute respiratory syndrome CoV 2 (SARS-CoV-2). Many tests have been developed, yet with variable speeds to first results, and are of unknown quality, particularly when considering the prediction of neutralizing capacity. The LIAISON SARS-CoV-2 S1/S2 IgG assay was designed to measure antibodies against the SARS-CoV-2 native S1/S2 proteins in a standardized automated chemiluminescence assay.

ABSTRACT BACKGROUND In the Covid-19 pandemic, highly selective serological testing is essential to define exposure to SARS-CoV-2 virus. Many tests have been developed, yet with variable speed to first result, and of unknown quality, particularly when considering the prediction of neutralizing capacity. OBJECTIVES/METHODS The LIAISON ® SARS-CoV-2 S1/S2 IgG assay was designed to measure antibodies against the SARS-CoV-2 native S1/S2 proteins in a standardized automated chemiluminescent assay. Clinical and analytical performance of the test were validated in an observational study using residual samples (>1500) with positive or negative Covid-19 diagnosis. RESULTS The LIAISON ® SARS-CoV-2 S1/S2 IgG assay proved highly selective and specific, and offers semiquantitative measures of serum or plasma levels of anti-S1/S2 IgG with neutralizing activity. The diagnostic sensitivity was 91.3% and 95.7% at >5 or ≥15 days from diagnosis respectively, and 100% when assessed against a neutralizing assay. The specificity ranged between 97% and 98.5%. The average imprecision of the assay was <5 % coefficient of variation. Assay performance at 2 different cut-offs was evaluated to optimize predictive values in settings with different % disease prevalence. CONCLUSIONS. The automated LIAISON ® SARS-CoV-2 S1/S2 IgG assay brings efficient, sensitive, specific, and precise serological testing to the laboratory, with the capacity to test large amounts of samples per day: first results are available within 35 minutes with a throughput of 170 tests/hour. The test also provides a semiquantitative measure to identify samples with neutralizing antibodies, useful also for a large scale screening of convalescent plasma for safe therapeutic use. IMPORTANCE With the worldwide advance of the COVID-19 pandemic, efficient, reliable and accessible diagnostic tools are needed to support public health officials and healthcare providers in their efforts to deliver optimal medical care, and articulate sound demographic policy. DiaSorin has developed an automated serology based assay for the measurement of IgG specific to SARS CoV-2 Spike protein, and tested its clinical performance in collaboration with Italian health care professionals who provided access to large numbers of samples from infected and non-infected individuals. The assay delivers excellent sensitivity and specificity, and is able to identify samples with high levels of neutralizing antibodies. This will provide guidance in assessing the true immune status of subjects, as well as meeting the pressing need to screen donors for high titer convalescent sera for subsequent therapeutic and prophylactic use.

Background and aims: Vitamin D exists as an inactive 25-hydroxyvitamin D (25(OH)D) in the bloodstream, which is converted to active 1,25-dihydroxyvitaminD (1,25(OH)(2)D) in target tissues. Cohort studies reporting cardiovascular disease among individuals with low vitamin D are inconsistent and solely measure 25(OH)D. Psoriasis, a chronic inflammatory disease, is a vitamin D deficient state and is associated with increased cardiovascular disease risk. While serum 25(OH)D is routinely measured, we hypothesized that measurement of 1,25(OH)2D in psoriasis may perform better than 25(OH)D in capturing cardiovascular risk. Methods: Consecutive psoriasis patients (N = 122) at baseline underwent FDG PET/CT and CCTA scans to measure visceral adipose volume, aortic vascular uptake of FDG, and coronary plaque burden respectively. Blood levels of both 1,25(OH)(2)D and 25(OH)D were measured by chemiluminescence (LIAISON XL DIaSorin, Stillwater, MN). Results: The psoriasis cohort was middle-aged (mean +/- SD: 49.6 +/- 13.0), predominantly male (n = 71, 58%), in majority Caucasians (n = 98, 80%), and had moderate-to-severe skin disease [psoriasis area severity index score, PASI score, med. (IQR): 5.5 (3.2-10.7)], with almost one-fourth of the cohort on biologic psoriasis therapy for skin disease management (n = 32, 27%) at baseline. Interestingly, serum levels of 1,25(OH)(2)D but not 25(OH)D were found to be inversely associated with visceral adipose, a marker of cardiometabolic risk in fully adjusted models (beta = -0.43, p = 0.026 and beta = -0.26 p = 0.13). Similarly, we found an inverse relationship between 1,25(OH)(2)D, but not 25(OH)D, and aortic vascular uptake of FDG independent of traditional risk factors (beta = -0.19, p = 0.01). Finally, we found that serum 1,25(OH)(2)D, but not 25(OH)D, was inversely associated with non-calcified coronary plaque burden, as measured by CCTA independent of traditional risk factors (beta = -0.18, p = 0.03). Conclusions: In conclusion, we demonstrate that low 1,25(OH)(2)D levels were associated with visceral adipose volume, vascular uptake of FDG and coronary plaque burden independent of traditional risk factors, suggesting that 1,25(OH)(2)D may better capture the cardiometabolic risk associated with vitamin D deficient states.

Mark Canney, Ognjenka Djurdjev, Mila Tang, Claudia Zierold, Frank Blocki, Fabrizio Bonelli, Myles Wolf, Adeera Levin Analytics, BC Renal Agency, Vancouver, BC, Canada, Scientific Affairs, Diasorin Inc., Stillwater, MN, United States, Medicine, Duke University, Durham, NC, United States, Nephrology Research, St. Paul’s Hospital, Vancouver, BC, Canada and Medicine, University of British Columbia, Vancouver, BC, Canada

Introduction: Psoriasis (PSO), a chronic inflammatory disease associated with increased Cardiovascular (CV) risk provides an ideal model to study the role of vitamin D, a known anti-inflammatory molecule in PSO associated CV disease. Vitamin D exists as inactive 25-hydroxyvitamin D (25(OH)D) in the bloodstream which is converted to active 1,25-dihydroxyvitaminD (1,25(OH)2D) in target tissues. Cohort studies reporting CV disease among individuals with low vitamin D are inconsistent and solely measure 25(OH)D. While serum 25(OH)D is routinely measured , we propose that measurement of 1,25(OH)2D may perform better than 25(OH)D as a surrogate for CV disease. Methods: Consecutive PSO patients (N=122) and healthy controls (N=35) underwent FDG PET/CT and CCTA scans to measure vascular inflammation/ abdominal adiposity volume and coronary plaque burden respectively. Blood levels of both 1,25(OH)2D and 25(OH)D were measured by chemiluminescence (LIASON XL DIaSorin, Stillwater, MN). Results: PSO patients were middle-aged, mostly male, had moderate PSO severity and were at low CV risk by 10-year Framingham risk. PSO patients had lower serum 1,25(OH)2D compared to healthy controls (mean±SEM: 52.4±1.4 pg/ml versus 57.5±2.0, p<0.037) but 25(OH)D was not significantly different (28.7±1.3 versus 27.3±2.2, p=0.30). 1,25(OH)2D, but not 25(OH)D was negatively associated with PASI score beyond adjustment for CV risk factors and systemic/ biological therapy (B=-0.20, p=0.043 vs. B=0.12, p=0.25). Furthermore, serum 1,25(OH)2D but not 25(OH)D was inversely associated with non-calcified coronary burden (B=-0.16, p<0.001 versus B=0.01, p=0.84), vascular inflammation (B=-0.24, p=0.007 versus B=-0.13, p=0.16) and visceral adiposity (B=-0.43, p=0.026 versus B=-0.26, p=0.13) independent of traditional risk factors and statin/PSO therapy. Conclusion: Our data support that active 1,25(OH)2D may more accurately capture cardiometabolic disturbance compared to inactive 25(OH)D in humans.