Cándido Juárez

This study tested the hypothesis that a more senescent immune system would predict a worse outcome in older patients hospitalized for community-acquired pneumonia (CAP). CAP has long been responsible for high rates of mortality and readmissions among older people. Although immunosenescence is a key factor in the increased susceptibility to infections, there are no related biomarkers currently available in clinical practice. In this context, the aim of this prospective study was to identify immunosenescence-related biomarkers to predict outcomes in patients older than 65 years hospitalized for CAP. We evaluated 97 patients admitted to our hospital for CAP in 2019 and 2020. All patients were followed for 1 year. Our findings showed that elevated levels of early differentiated CD28+ CD27+ T cells at admission were associated with better short (2 months) and long-term (1 year) outcomes in terms of mortality and readmissions. Early differentiated CD28+ CD27+ CD4+ T cell counts were even better long-term predictors. In conclusion, early differentiated CD28+ CD27+ T cells could be useful biomarkers to identify high-risk older patients with CAP, helping clinicians with risk stratification and follow-up.

It is essential to find new biomarkers for severity stratification of patients with coronavirus disease (COVID-19). Growth differentiation factor 15 (GDF-15) is upregulated in pathological conditions that involve inflammation and/or oxidative stress. We determined circulating levels of GDF-15 and correlated them with clinical and laboratory parameters reflecting severity in 84 patients with COVID-19, finding that GDF-15 levels were higher in both patients than in 20 healthy controls and were higher in patients with poorer respiratory function. GDF-15 levels also correlated with interleukin-6, C-reactive protein, ferritin and D-dimer levels and with neutrophilia and lymphopenia. Of all the analysed biomarkers, GDF-15 showed the best area under the receiver operating characteristics curve in identifying patients with poor respiratory function. In conclusion, our data support GDF-15 as a biomarker associated with pulmonary impairment in COVID-19 and so can potentially be useful in stratifying COVID-19 cases by severity.

Introduction: Grown Differentiation Factor-15 (GDF-15), also known as Macrophage Inhibitory cytokine-1 (MIC-1), is a Transforming Growth Factor (TGF)-β superfamily member secreted in response to pro-inflammatory mediators and oxidative stress and associates with inflammation and cellular damage. Aim and Objectives: to study the role of GDF-15 as a risk factor in patients with SARS-CoV-2 pneumonia admitted to hospital. Methods: 81 patients with COVID-19 and 20 healthy controls (HC) were included. GDF-15 was quantified by ELISA (R&D Systems) and compared to other inflammatory and respiratory parameters at admission. Results: We found higher levels of GDF-15 in COVID-19 patients in comparison with HC: 2042 (1396-3054) vs. 582 (370.8-807.6) pg/ml; p<0.0001. GDF-15 levels were higher in patients with low oxygen saturation (SaO2) (p=0.004) and with low SaO2/inspired fraction of oxygen (SaFi) ratio, (p=0.003). Differences in PCR, DD and ferritin values were observed when segregating according to SaO2 but not when segregating according to SaFi. A positive correlation between GDF-15 levels and PCR (p<0.001), ferritin (p=0.011), D-dimer (DD) (p=0.003) IL-6 (p<0.001) was found. Conclusions: GDF-15 levels are elevated in COVID-19 patients in comparison with HC. Those patients with respiratory worsening (SaFi<300) had the highest levels of GDF-15, but no differences in PCR, DD or ferritin. So, GDF-15 could be a good biomarker of respiratory deterioration to be used in clinical practice.

Objectives: Anti-TIF-1γ autoantibody detection is important for cancer screening in patients with dermatomyositis. The gold standard for anti-TIF-1γ detection, immunoprecipitation, is only available from a few specialized laboratories worldwide, so commercial ELISA/immunoblot tests have emerged in recent years. To analyze their usefulness in diagnosing cancer-associated dermatomyositis, we compared Euroimmun Euroline profile with our previously validated in-house immunoblot assay with human recombinant TIF-1γ. Methods: We included 308 adult patients from Hospital de la Santa Creu I Sant Pau and Vall Hebrón Hospital (Barcelona, Spain) tested for anti-TIF-1γ autoantibodies using the Euroline profile and an in-house immunoblot assay. Results: A total of 27 anti-TIF-1γ were detected by the Euroline and 12 by the in-house assay. Fair agreement was observed between Euroline and the in-house immunoblot Cohen’s kappa 0.3163. Expected prevalence of anti-TIF-1γ autoantibodies was observed for the two methods for dermatomyositis and undifferentiated connective tissue diseases, but unexpectedly high prevalence of anti-TIF-1γ autoantibodies was detected by Euroline compared to the in-house immunoblot for other diseases (16.5% Euroline vs 0.8% in-house immunoblot, pConclusion: We recommend using a second validated method to confirm Euroline-detected anti-TIF-1γ antibodies when the dermatomyositis diagnosis is not definitive. Furthermore, in the context of definite DM diagnosis with negative anti-TIF-1γ antibodies by Euroline and no other myositis specific antibody, is also recommendable to confirm by a second validated method.

Vitiligo pathophysiology is mediated by antigen‐specific cytotoxic T cells. Environmental stressors cause susceptible melanocytes to secrete damage‐associated molecular patterns (DAMPs). DAMPs are recognized by receptors such as the endocytic low‐density lipoprotein receptor‐related protein (LRP1/CD91), expressed in antigen‐presenting cells, which activate self‐reactive CD8+ T cells, leading to melanocyte destruction. Within this response, interferon gamma triggers production of cytokine CXCL10, recruiting more activated T cells causing further melanocytic damage. We hypothesized that expression of LRP1/CD91 was higher in vitiligo patients compared to non‐vitiligo individuals. And further that levels/expression of CXCL10 in plasma were linked to disease severity. We enrolled forty individuals in this study: 18 patients with vitiligo and 22 healthy volunteers. We assessed LRP1/CD91 expression and plasma CXCL10 in patients with vitiligo and healthy volunteers. Additionally, vitiligo patients received combined treatment for 16 weeks following which the said parameters were reassessed. Vitiligo Area Scoring Index was calculated before and after treatment for these patients. Analysis of LRP1/CD91 MFI values in monocytes from vitiligo patients showed high surface levels of LRP1/CD91 than from healthy volunteers (10.50 ± 0.77 vs. 6.55 ± 0.77 MFI units, p < 0.001). This expression did not change after treatment. Plasma levels of CXCL10 were higher in vitiligo patients than healthy volunteers (93.78 ± 7.73 vs. 40.17 ± 6.25 pg/ml). The patients with a good clinical response to treatment had a parallel reduction in plasma CXCL10 levels (105.8 ± 18.44 vs. 66.13 ± 4.87 pg/ml) before and after treatment. LRP1/CD91 expression may reflect susceptibility to vitiligo. Plasma levels of CXCL10 can represent a biomarker for monitoring treatment response. LRP1 and CXCL10 may represent therapeutic targets.

A distinctive new indirect immunofluorescence pattern in liver tissue has been associated with anti‐HMGCR autoantibodies. It is known as HALIP (HMGCR Associated Liver Immunofluorescence Pattern). In this study, we furthered the original studies to demonstrate the association of anti‐HMGCR antibodies with the HALIP. Human anti‐HMGCR antibodies from patients’ sera were purified and incubated with rat triple tissue (kidney/stomach/liver). A characteristic HALIP was observed. Additionally, a colocalization assay of human anti‐HMGCR antibodies with rabbit polyclonal anti‐HMGCR antibodies showed colocalization of both immunofluorescence patterns. This study confirms that the HALIP is due to human anti‐HMGCR antibodies.

Background: The LRP1 (CR9) domain and, in particular, the sequence Gly¹¹²⁷-Cys¹¹⁴⁰ (P3) plays a critical role in the binding and internalization of aggregated LDL (agLDL). We aimed to evaluate whether immunization with P3 reduces high-fat diet (HFD)-induced atherosclerosis.

Antibodies against myelin-associated glycoprotein (MAG) almost invariably appear in the context of an IgM monoclonal gammopathy associated neuropathy. Very few cases of anti-MAG neuropathy lacking IgM-monoclonal gammopathy have been reported. We investigated the presence of anti-MAG antibodies in 69 patients fulfilling diagnostic criteria for CIDP. Anti-MAG antibodies were tested by ELISA and confirmed by immunohistochemistry. We identified four (5.8%) anti-MAG positive patients without detectable IgM-monoclonal gammopathy. In two of them, IgM-monoclonal gammopathy was detected at 3 and 4-year follow-up coinciding with an increase in anti-MAG antibodies titers. In conclusion, anti-MAG antibody testing should be considered in chronic demyelinating neuropathies, even if IgM-monoclonal gammopathy is not detectable.

Probiotics can modulate gut microbiota, intestinal permeability, and immune response and could therefore improve cognitive dysfunction and help avoid potential consequences, such as falls, in patients with cirrhosis. The aim of this study was to evaluate the effect of a multistrain probiotic on cognitive function, risk of falls, and inflammatory response in patients with cirrhosis. Consecutive outpatients with cirrhosis and cognitive dysfunction (defined by a Psychometric Hepatic Encephalopathy Score [PHES] < −4) and/or falls in the previous year were randomized to receive either a sachet of a high‐concentration multistrain probiotic containing 450 billion bacteria twice daily for 12 weeks or placebo. We evaluated the changes in cognitive function (PHES); risk of falls (Timed Up and Go [TUG] test, gait speed, and incidence of falls); systemic inflammatory response; neutrophil oxidative burst; intestinal barrier integrity (serum fatty acid–binding protein 6 [FABP‐6] and 2 [FABP‐2] and zonulin and urinary claudin‐3); bacterial translocation (lipopolysaccharide‐binding protein [LBP]); and fecal microbiota. Thirty‐six patients were included. Patients treated with the probiotic (n = 18) showed an improvement in the PHES (P = 0.006), TUG time (P = 0.015) and gait speed (P = 0.02), and a trend toward a lower incidence of falls during follow‐up (0% compared with 22.2% in the placebo group [n = 18]; P = 0.10). In the probiotic group, we observed a decrease in C‐reactive protein (P = 0.01), tumor necrosis factor alpha (P = 0.01), FABP‐6 (P = 0.009), and claudin‐3 (P = 0.002), and an increase in poststimulation neutrophil oxidative burst (P = 0.002). Conclusion: The multistrain probiotic improved cognitive function, risk of falls, and inflammatory response in patients with cirrhosis and cognitive dysfunction and/or previous falls.