NK degranulation plays an important role in the cytotoxic activity of innate immunity in the clearance of intracellular infections and is an important factor in the outcome of the disease. This work ...has studied NK degranulation and innate immunological profiles and functionalities in COVID-19 patients and its association with the severity of the disease. A prospective observational study with 99 COVID-19 patients was conducted. Patients were grouped according to hospital requirements and severity. Innate immune cell subpopulations and functionalities were analyzed. The profile and functionality of innate immune cells differ between healthy controls and severe patients; CD56dim NK cells increased and MAIT cells and NK degranulation rates decreased in the COVID-19 subjects. Higher degranulation rates were observed in the non-severe patients and in the healthy controls compared to the severe patients. Benign forms of the disease had a higher granzymeA/granzymeB ratio than complex forms. In a multivariate analysis, the degranulation capacity resulted in a protective factor against severe forms of the disease (OR: 0.86), whereas the permanent expression of NKG2D in NKT cells was an independent risk factor (OR: 3.81; AUC: 0.84). In conclusion, a prompt and efficient degranulation functionality in the early stages of infection could be used as a tool to identify patients who will have a better evolution.
The Th1/Th2 balance plays a crucial role in the progression of different pathologies and is a determining factor in the evolution of infectious diseases. This work has aimed to evaluate the early, or ...on diagnosis, T-cell compartment response, T-helper subsets and anti-SARS-CoV-2 antibody specificity in COVID-19 patients and to classify them according to evolution based on infection severity. A unicenter, randomized group of 146 COVID-19 patients was divided into four groups in accordance with the most critical events during the course of disease. The immunophenotype and T-helper subsets were analyzed by flow cytometry. Asymptomatic SARS-CoV-2 infected individuals showed a potent and robust Th1 immunity, with a lower Th17 and less activated T-cells at the time of sample acquisition compared not only with symptomatic patients, but also with healthy controls. Conversely, severe COVID-19 patients presented with Th17-skewed immunity, fewer Th1 responses and more activated T-cells. The multivariate analysis of the immunological and inflammatory parameters, together with the comorbidities, showed that the Th1 response was an independent protective factor for the prevention of hospitalization (OR 0.17, 95% CI 0.03-0.81), with an AUC of 0.844. Likewise, the Th1 response was found to be an independent protective factor for severe forms of the disease (OR 0.09, 95% CI: 0.01-0.63,
= 0.015, AUC: 0.873). In conclusion, a predominant Th1 immune response in the acute phase of the SARS-CoV-2 infection could be used as a tool to identify patients who might have a good disease evolution.
The presence of antiphospholipid antibodies (aPLs) is associated with antiphospholipid syndrome (APS), characterized by thrombosis and obstetric morbidity. aPLs included in APS classification ...criteria are lupus anticoagulant, anti-cardiolipin and anti-beta-2-glycoprotein-I of IgG or IgM isotypes. Enzyme-linked immunosorbent assay is the most used diagnostic technique to determine aPLs. Recently, new automated technologies mainly based in antigen-coated beads have been developed. The aim is to compare a fluorescence enzyme immunoassay (M1) and an antigen-coated bead assay (M2) in obstetric and thrombotic APS patients. All samples from the first 1020 patients received in the Immune Service Laboratory (Hospital 12 de Octubre) during the recruitment period, without exclusions, were analysed for aPLs. The weighted kappa for both methods in all the patients was 0.39 (0.30-0.47). Agreement increased to 0.56 (0.38-0.73) in patients with autoimmune disease. Sensitivity and specificity obtained for M1 were 17.1% and 89.3%, respectively, and 12.7% and 91.4% for M2. The sensibility and specificity of IgG isotypes were higher than the IgM ones. Regarding obstetric patients, M1 obtained significant diagnostic performance and had more sensitivity 23.75 (14.95-34.58) compared to M2 12.50 (6.16-21.79). In conclusion, clinical suspicion-based method selection for aPLs should be considered. To identify obstetric APS patients, solid phase methods remain more preferable.
Introduction Influenza virus infection can cause a range of clinical symptoms, including respiratory failure (RF) and even death. The mechanisms responsible for the most severe forms of the disease ...are not yet well understood. The objective is to assess the initial immune response upon admission and its potential impact on infection progression. Methods We conducted a prospective observational study of patients with influenza virus infection who required admission to a tertiary hospital in the 2017/18 and 2018/19 flu seasons. Immune markers, surrogate markers of neutrophil activation, and blood levels of DNase I and Apolipoprotein-H (ApoH) were determined in the first serum sample available during hospital care. Patients were followed until hospital discharge or death. Initially, 792 patients were included. From this group, 107 patients with poor evolution were selected, and a random control group was matched by day of admission. Results Patients with poor outcomes had significantly reduced ApoH levels, a soluble protein that regulate both complement and coagulation pathways. In multivariate analysis, low plasma levels of ApoH (OR:5.43; 2.21-13.4), high levels of C- reactive protein (OR:2.73: 1.28-5.4), hyperferritinemia (OR:2.83; 1.28-5.4) and smoking (OR:3.41; 1.04-11.16), were significantly associated with a worse prognosis. RF was independently associated with low levels of ApoH (OR: 5.12; 2.02-1.94), while high levels of IL15 behaved as a protective factor (OR:0.30; 0.12-0.71). Discussion Therefore, in hospitalized influenza patients, a dysregulated early immune response is associated with a worse outcome. Adequate plasma levels of ApoH are protective against severe influenza and RF and High levels of IL15 protect against RF.
Background: COVID-19 clinical features include a hypercoagulable state that resembles the antiphospholipid syndrome (APS), a disease characterized by thrombosis and presence of antiphospholipid ...antibodies (aPL). The relationship between aPL-presence and the appearance of thrombi as well as the transience or permanence of aPL in COVID-19 patients is not sufficiently clear. Methods: A group of 360 COVID-19 patients were followed-up for 6 months. Classic aPL, anti-B2GPI IgA, anti-phosphatidylserine/prothrombin IgG/M and anti-SARS-CoV-2 antibodies were determined at acute phase and >12 weeks later. The reference group included 143 healthy volunteers of the same age-range distribution. Results: aPL prevalence was similar in COVID-19 patients and the reference population. aPL presence in both determinations was significantly associated with thrombosis (OR: 2.33 and 3.71), strong agreement being found for classic aPL and anti-B2GPI IgA (Weighted kappa: 0.85–0.91). Thrombosis-associated aPL occurred a median of 17 days after hospital admission (IQR: 6–28) vs. 4 days for the rest (IQR: 3–7). Although anti-SARS-CoV-2 antibodies levels increased during convalescence, aPL hardly changed. Conclusions: Most COVID-19 patients would carry these aPL before the infection. At least two mechanisms could be behind thrombosis, early immune-dysregulation-mediated thrombosis after infection and belated-aPL-mediated thrombosis, with SARS-CoV-2 behaving as a second hit.
ObjectiveTo compare characteristics, pregnancies and treatments during pregnancies of seronegative and seropositive antiphospholipid syndrome (APS), to analyse factors associated with obstetrical ...outcome.Patients and methodsInclusion criteria were: (1) thrombotic and/or obstetrical APS (Sydney criteria); (2) absence of conventional antiphospholipid antibodies (APL); (3) at least one persistent non-conventional APL among IgA anticardiolipin antibodies, IgA anti-B2GPI, anti-vimentin G/M, anti-annexin V G/M, anti-phosphatidylethanolamine G/M and anti-phosphatidylserine/prothrombin G/M antibodies. The exclusion criteria were: (1) systemic lupus erythematosus ( SLE) or SLE-like disease; and (2) other connective tissue disease.ResultsA total of 187 women (mean 33±5 years) with seronegative APS were included from 14 centres in Austria, Spain, Italy, Slovenia and France and compared with 285 patients with seropositive APS. Seronegative APS has more obstetrical rather than thrombotic phenotypes, with only 6% of venous thrombosis in comparison to seropositive APS. Cumulative incidence of adverse obstetrical events was similar in seronegative and seropositive APS patients, although higher rates of intrauterine deaths (15% vs 5%; p=0.03), of preeclampsia (7% vs 16%, p=0.048) and lower live birth term (36±3 vs 38±3 weeks of gestation; p=0.04) were noted in seropositive APS. The cumulative incidence of adverse obstetrical events was significantly improved in treated versus untreated seronegative APS (log rank<0.05), whereas there was no difference between patients who received aspirin or aspirin-low-molecular weighted heparin combination.ConclusionSeveral non-criteria APL can be detected in patients with clinical APS features without any conventional APL, with various rates. The detection of non-criteria APL and thus the diagnosis of seronegative APS could discuss the therapeutic management similar to seropositive APS, but well-designed controlled studies are necessary.
Ischemic stroke is the most common and severe arterial thrombotic event in Antiphospholipid syndrome (APS). APS is an autoimmune disease characterized by the presence of thrombosis and ...antiphospholipid antibodies (aPL), which provide a pro-coagulant state. The aPL included in the classification criteria are lupus anticoagulant, anti-cardiolipin (aCL) and anti-β2-glycoprotein-I antibodies (aB2GPI) of IgG and IgM isotypes. Extra-criteria aPL, especially IgA aB2GPI and IgG/IgM anti-phosphatidylserine/prothrombin antibodies (aPS/PT), have been strongly associated with thrombosis. However, their role in the general population suffering from stroke is unknown. We aim (1) to evaluate the aPL prevalence in ischemic stroke patients, (2) to determine the role of aPL as a risk factor for stroke, and (3) to create an easy-to-use tool to stratify the risk of ischemic stroke occurrence considering the presence of aPL and other risk factors.
A cohort of 245 consecutive ischemic stroke patients was evaluated in the first 24 h after the acute event for the presence of classic aPL, extra-criteria aPL (IgA aB2GPI, IgG, and IgM aPS/PT) and conventional cardiovascular risk factors. These patients were followed-up for 2-years. A group of 121 healthy volunteers of the same age range and representative of the general population was used as reference population. The study was approved by the Ethics Committee for Clinical Research (Reference numbers CEIC-14/354 and CEIC-18/182).
The overall aPL prevalence in stroke patients was 28% and IgA aB2GPI were the most prevalent (20%). In the multivariant analysis, the presence of IgA aB2GPI (OR 2.40, 95% CI: 1.03-5.53), dyslipidemia (OR 1.70, 95% CI: 1.01-2.84), arterial hypertension (OR 1.82, 95% CI: 1.03-3.22), atrial fibrillation (OR 4.31, 95% CI: 1.90-9.78), and active smoking (OR 3.47, 95% CI: 1.72-6.99) were identified as independent risk factors for ischemic stroke. A risk stratification tool for stroke was created based on these factors (AUC: 0.75).
IgA aB2GPI are an important independent risk factor for ischemic stroke. Evaluation of aPL (including extra-criteria) in cardiovascular risk factor assessment for stroke can potentially increase the identification of patients at risk of thrombotic event, facilitating a decision on preventive treatments.
Mortality of patients on hemodialysis (HD) remains very high despite recent improvements in HD techniques. Cardiovascular (CV) complications and infections are the main causes of death. Some studies ...suggest that disturbances in the immune system could play a role in this disproportionate mortality, through the links of immunity with inflammation and propensity to infections. However, few studies have addressed the role of lymphocyte populations and the global and CV mortality of HD patients.
To analyze the relationship of peripheral blood lymphocyte populations (PBLP) and all-cause and CV mortality of HD patients.
We design a prospective observational single center study in a cohort of HD prevalent patients. PBLP were analyzed at baseline and after 1 year and patients were followed for a 5-year period. Main outcomes were all-cause and CV mortality.
One hundred and four patients (51% male, mean age 64.8 ± 15 years) were included. Follow-up was 18 (7-47) months. Fifty-five patients (52.8%) died, main causes of death being CVD (40%) and infections (29.1%). Low total lymphocyte counts were found in 47 patients (45.2%), and the most frequency lymphopenias were CD19
B-cell (57.7%), CD3
(40.4%), and CD4
(36.5%). After 1 year, all determinations were lower except CD56
CD16
CD3
natural killer. Patient survival was significantly lower in patients with a CD19
B-cell count < 100 cells/μL at baseline as compared to patients with CD19
B-cell ≥ 100 cells/μL counts at the end of follow-up (16.5 vs 54%,
= 0.003). By multivariable analysis, age, history of CV disease, Charlson index, a KT/V < 1.2, and a CD19
B-cell count < 100 cells/μL at baseline and after 1-year were factors associated with of all-cause mortality. A CD19
B-cell count < 100 cells/μL at baseline was associated with CV mortality.
CD19
B-cell lymphopenia is very common among HD patients, and it could be an independent predictor of all-cause and CV mortality. More studies are needed to confirm these findings.
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