Introduction
Primary antibody deficiencies (PAD) are inborn defects of the immune system that result in increased susceptibility to infections. Despite the reduced response to vaccination, PAD ...patients still benefit from it by reducing the risk of severe infections and complications. SARS-CoV-2 vaccines are recommended in PAD patients, but their immune effects are poorly studied. Here, we analyze virus-specific T-cell responses in PAD patients after booster vaccination against SARS-CoV-2.
Patients and methods
The study included 57 adult PAD patients on long-term immunoglobulin replacement therapy (IgRT) diagnosed with X-linked agammaglobulinemia (XLA; n = 4), common variable immunodeficiency (CVID; n = 33), isotype defects or IgG subclass deficiency (n = 6), and unclassified IgG deficiency (n = 14). Of those, 49 patients (86%) received vaccination against SARS-CoV-2 using mRNA vaccine (Pfizer-BioNTech). T-cell responses were assessed at a median of 21 (13 – 30) weeks after the booster dose (mainly the third dose) using commercially available interferon-gamma release assay (IGRA) with recombinant SARS-CoV-2 spike S1 protein.
Results
Vaccinated PAD patients showed an increased (3.8-fold, p = 0.004) release of IFN-γ upon S1 stimulation. In this group, we also documented higher serum levels of anti-SARS-CoV-2 IgG (4.1-fold, p = 0.01), although they were not associated with IGRA results. Further subgroup analysis revealed very similar IGRA responses in CVID and unclassified IgG deficiencies that were 2.4-fold increased compared to XLA and 5.4-fold increased compared to patients with isotype defects or IgG subclass deficiencies (e.g., vs. CVID: p = 0.016). As expected, CVID and XLA patients showed decreased serum titers of anti-SARS-CoV-2 antibodies compared to other studied groups (e.g., CVID vs. unclassified IgG deficiency: 4.4-fold, p = 0.006). The results did not depend directly on IgRT mode or dose, number of vaccine doses and time from the last booster dose, and clinical manifestations of PAD. Interestingly, anti-SARS-CoV-2 titers were positively correlated with serum immunoglobulin levels before IgRT (e.g., for IgA: r = 0.45, p<0.001; for IgG: r = 0.34, p = 0.009) and the percentage of peripheral blood NK cells (r = 0.48, p<0.001).
Conclusions
Our results documented satisfactory
in vitro
cellular immune response in PAD patients after booster SARS-CoV-2 vaccination. Therefore, even patients with agammaglobulinemia should benefit from vaccination due to the apparent induction of cell-mediated immunity, which, together with IgRT, grants comprehensive protection against the pathogen.
Central retinal artery occlusion (CRAO) is a common cause of blindness and visual morbidity. In the majority of cases, it is related to thrombotic embolism. Nevertheless, the role of inherited or ...acquired thrombophilic risk factors in CRAO pathogenesis has not been comprehensively studied.
In 126 CRAO patients (66 52.4% men, median age 55 range: 18-80 years) and 107 matched controls (56 52.3% men, median age 53 range: 34-78 years) we evaluated classical atherosclerotic risk factors, including serum lipid profile and glucose level, analyzed intima-media complex thickness (IMT) of external carotid arteries, and performed transthoracic echocardiography. Furthermore, we established the prevalence of inherited and acquired thrombophilic risk factors, such as factor V Leiden (FVL) and prothrombin 20210 G/A genetic variants, plasma activity of factor (F) VIII, protein C and antithrombin activity, and free protein S levels. We also assessed the presence of antiphospholipid antibodies (APLA) and evaluated blood homocysteine in all enrolled subjects. Additionally, we estimated the occurrence of Val34Leu polymorphism of the A subunit of coagulation factor XIII (FXIII-A) in both groups as a potential thrombosis-protecting factor.
Among traditional atherosclerotic risk components, obesity/overweight and hypercholesterolemia were the most common in the CRAO group and occurred in 103 (81.7%) and 85 (67.5%) patients, respectively. CRAO patients also had elevated IMT and altered echocardiographic parameters, indicating diastolic cardiac dysfunction. In thrombophilia investigations, at least one laboratory risk factor occurred in 72.2% (n = 91) of CRAO patients, with APLA as the most frequent, detected in 38.1% (n = 48) of them (almost seven times more frequent than in controls, p < 0.001). Deficiencies in protein C activity and free protein S levels were also common in the CRAO group, reported in 17.5% (n = 22) and 19.8% (n = 25) of patients, respectively. Interestingly, among two analyzed prothrombotic genetic variants, only the FVL was related to CRAO, with the allelic frequency 2.4 times more prevalent than in controls (p = 0.044). Finally, the CRAO group was characterized by hyperhomocysteinemia, almost twice as common as in controls (p = 0.026). Antithrombin deficiency, elevated FVIII, and FXIII-A Val34Leu polymorphism were not associated with CRAO.
Our findings suggest that thrombophilia plays a vital role in the pathogenesis of CRAO. Thus, proper laboratory screening should be considered in the primary and secondary prevention of those episodes, with implementing appropriate therapy as needed.
The work of teachers during the COVID-19 pandemic created additional challenges and required them to go beyond conventional teaching methods, which in turn required teachers to be more resilient and ...caused stress and excessive workload. The aim of the study was to assess the level of occupational burnout, the sense of job satisfaction and the self-efficacy of primary and secondary school teachers working during the COVID-19 pandemic in Poland.
This is a cross-sectional descriptive study conducted among 412 teachers from randomly selected primary and secondary schools in the Podkarpacie region in Poland. The questionnaire contained socio-demographic data of the respondents and three standardized scales: The Scale of Job Satisfaction (SJS), General Self-Efficacy Scale (GSES) and Arbeitsbesorgenes Verhaltens und Erlebenmuster (AVEM). The Shapiro-Wilk, Kruskal-Wallis and Mann-Whitney
-test were used. Statistical analysis was performed with Statistica TIBCO 13.3 and R (version 3.6.1) software.
The satisfaction with the work of the surveyed teachers was average in the job satisfaction scale. The vast majority of the surveyed teachers presented type
overburdened risk type) of work-related behavior, and type
(overburdened risk type) in which the probability of burnout is very high. The feeling of self-effectiveness determines the level of job satisfaction and the level of professional burnout among the surveyed teachers. Job satisfaction had a statistically significant impact on the assessment of self-efficacy of the surveyed teachers (
< 0.0001). The types of work-related behavior have a statistically significant impact on the assessment of the teachers' own effectiveness (
< 0.0001).
There is a close relationship between teachers' level of self- efficacy, job satisfaction and, therefore it may predispose them to the occurrence of burnout syndrome in the future. Support for this professional group is needed. These findings may be important for education policy, teacher's practice, and subsequent research. Ultimately, the study may provide some suggestions for methodological and educational strategies.
Samples of leaves, flowers, soil, pollen, bee workers, bee brood, honey, and beeswax were collected to assess the possibility of a transfer of captan, thiacloprid, penthiopyrad, and λ-cyhalothrin ...from apple trees of Idared variety to honey bee (
Apis mellifera
) hives. Chemical analyses were performed using the Agilent 7890 Gas Chromatograph equipped with the Micro-cell Electron Capture Detector. It was found that significant amounts of penthiopyrad, the active ingredient of Fontelis 200 SC, were present in leaves, flowers, pollen, bee workers, and beeswax. Simultaneously, captan was present in the brood, worker bees, and honey samples. Significant levels of the captan residues were also detected on the soil surface. In honey samples, captan residue levels exceeded the acceptable standard, reaching 160% of its maximum residue level. However, in no case the amounts of captan, thiacloprid, penthiopyrad, and λ-cyhalothrin ingested with honey by an adult consumer exceeded the level of 0.02% of the acceptable daily intake. Despite the trace amounts of pesticide residues in honey samples collected during the field trial, bee honey consumption can be considered safe. An adult consumer can safely consume about 16 kg of honey.
Background
Lupus nephritis (LN) manifests systemic lupus erythematosus (SLE) and is characterized by various clinical and laboratory features. This study aimed to comprehensively evaluate the ...characteristics of LN patients according to the time of LN diagnosis: early-onset (LN diagnosed within one year from SLE diagnosis) vs. delayed-onset (LN diagnosed more than one year after SLE diagnosis).
Methods
We conducted a retrospective analysis of medical records from all SLE patients treated at the University Hospital in Kraków, Poland, from 2012 to 2022. We collected data on demographic, clinical, and laboratory characteristics, including histological findings, treatment modalities, and disease outcomes. Statistical analyses were performed to identify factors impacting LN development and prognosis.
Results
Among 331 LN patients, early-onset was diagnosed in 207 (62.54%) and delayed-onset was documented in 122 cases (36.86%). In 2 (0.6%) LN cases, the time of first kidney manifestation in the SLE course was unknown. Delayed-onset LN had a higher female-to-male ratio and younger age at SLE diagnosis. This group was associated with more severe clinical manifestations. In turn, studied subgroups did not differ in internist comorbidities, kidney histopathology, and family history regarding autoimmune diseases. Delayed-onset LN exhibited a higher frequency of anti-dsDNA, anti-Smith, anti-Ro, anti-RNP, and anti-cardiolipin IgG autoantibodies. During a 14-year follow-up period, 16 patients died. Mortality rate and causes of death were comparable in both analyzed subgroups.
Conclusions
More severe clinical manifestations in delayed-onset LN prompt strict monitoring of non-LN SLE patients to diagnose and treat kidney involvement early. Also, recognizing the higher frequency of autoantibodies such as anti-dsDNA or anti-Smith in delayed-onset LN underscores the potential value of autoantibody profiling as a diagnostic and prognostic tool.
COVID-19 is associated with an increased thromboembolic risk. However, the mechanisms triggering clot formation in those patients remain unknown.
In 118 adult Caucasian severe but non-critically ill ...COVID-19 patients (median age 58 years; 73 % men) and 46 controls, we analyzed in vitro plasma thrombin generation profile (calibrated automated thrombogram CAT assay) and investigated thrombophilia-related factors, such as protein C and antithrombin activity, free protein S level, presence of antiphospholipid antibodies and factor V Leiden R506Q and prothrombin G20210A mutations. We also measured circulating von Willebrand factor (vWF) antigen and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) antigen and activity. In patients, blood samples were collected on admission to the hospital before starting any therapy, including heparin. Finally, we examined the relationship between observed alterations and disease follow-up, such as thromboembolic complications.
COVID-19 patients showed 17 % lower protein C activity, 22 % decreased free protein S levels, and a higher prevalence of positive results for IgM anticardiolipin antibodies. They also had 151 % increased vWF, and 27 % decreased ADAMTS13 antigens compared with controls (p < 0.001, all). On the contrary, thrombin generation potential was similar to controls. In the follow-up, pulmonary embolism (PE) occurred in thirteen (11 %) patients. They were characterized by a 55 % elevated D-dimer (p = 0.04) and 2.7-fold higher troponin I (p = 0.002) during hospitalization and 29 % shorter time to thrombin peak in CAT assay (p = 0.009) compared to patients without PE.
In COVID-19, we documented prothrombotic abnormalities of peripheral blood. PE was characterized by more dynamic thrombin generation growth in CAT assay performed on admittance to the hospital.
Abstract Objective Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a variable clinical manifestation, potentially leading to death. Importantly, patients with SLE have an ...increased risk of neoplastic disorders. Thus, this study aimed to comprehensively evaluate the clinical and laboratory characteristics of patients with SLE and with or without malignancy. Methods We conducted a retrospective analysis of medical records of 932 adult Caucasian patients with SLE treated at the University Hospital in Kraków, Poland, from 2012 to 2022. We collected demographic, clinical, and laboratory characteristics, but also treatment modalities with disease outcomes. Results Among 932 patients with SLE, malignancy was documented in 92 (9.87%), with 7 (7.61%) patients experiencing more than one such complication. Non-hematologic malignancies were more prevalent ( n = 77, 83.7%) than hematologic malignancies ( n = 15, 16.3%). Patients with SLE and malignancy had a higher mean age of SLE onset and a longer mean disease duration than patients without malignancy ( p < 0.001 and p = 0.027, respectively). The former group also presented more frequently with weight loss (odds ratio OR = 2.62, 95% confidence interval CI 1.61–4.23, p < 0.001), fatigue/weakness (OR = 2.10, 95% CI 1.22–3.77, p = 0.005), and fever (OR = 1.68, 95% CI 1.06–2.69, p = 0.024). In the malignancy-associated group, we noticed a higher prevalence of some clinical manifestations, such as pulmonary hypertension (OR = 3.47, 95% CI 1.30–8.42, p = 0.007), lung involvement (OR = 2.64, 95% CI 1.35–4.92, p = 0.003) with pleural effusion (OR = 2.39, 95% CI 1.43–3.94, p < 0.001), and anemia (OR = 2.24, 95% CI 1.29–4.38, p = 0.006). Moreover, the patients with SLE and malignancy more frequently had internal comorbidities, including peripheral arterial obliterans disease (OR = 3.89, 95% CI 1.86–7.75, p < 0.001), myocardial infarction (OR = 3.08, 95% CI 1.41–6.30, p = 0.003), heart failure (OR = 2.94, 95% CI 1.30–6.17, p = 0.005), diabetes mellitus (OR = 2.15, 95% CI 1.14–3.91, p = 0.011), hypothyroidism (OR = 2.08, 95% CI 1.29–3.34, p = 0.002), arterial hypertension (OR = 1.97, 95% CI 1.23–3.23, p = 0.003), and hypercholesterolemia (OR = 1.87, 95% CI 1.18-3.00, p = 0.006). Patients with SLE and malignancy were treated more often with aggressive immunosuppressive therapies, including cyclophosphamide (OR = 2.07, 95% CI 1.30–3.28, p = 0.002), however median cumulative cyclophosphamide dose in malignancy-associated SLE subgroup was 0 g (0–2 g). Interestingly, over a median follow-up period of 14 years (ranges: 8–22 years) a total of 47 patients with SLE died, with 16 cases (5.28%) in the malignancy-associated SLE group and 31 cases (5.73%) in the non-malignancy SLE group ( p = 0.76). The most common causes of death were infections (21.28%) and SLE exacerbation (8.51%). Conclusion The study highlights the relatively frequent presence of malignancies in patients with SLE, a phenomenon that demands oncological vigilance, especially in patients with a severe clinical course and comorbidities, to improve long-term outcomes in these patients.
Systemic sclerosis (SSc) is a rare connective tissue disorder of unknown etiology characterized by organ fibrosis and microcirculation dysfunction. Emerging evidence suggests that SSc is related to ...increased oxidative stress, which contributes to further tissue and vascular damage.
Oxidative stress response in the peripheral blood was assessed in patients with SSc (n = 55) and well-matched controls (n = 44) using real-time monitoring of protein hydroperoxide (HP) formation by the coumarin boronic acid (CBA) assay. We also analyzed the relationship between HP generation and SSc clinics, systemic inflammation, and cellular fibronectin, an emerging biomarker of endothelial damage.
SSc was characterized by a significantly faster (2-fold) fluorescent product generation in the CBA assay and higher cumulative HP formation (3-fold) compared to controls (p<0.001, both). The dynamics of HP generation were not associated with the form of the disease (diffuse vs. limited SSc), current immunosuppressive therapy use, presence of abnormal nailfold capillaries, and autoantibody profile. Still, it was enhanced in patients with more severe illness and certain clinical manifestations (i.e., pulmonary hypertension, digital ulcers, and cyclophosphamide treatment) and in smokers (current or past). Higher serum CRP, blood eosinophil count, and cellular fibronectin with lower hemoglobin levels were independent determinants of increased HP formation.
Our data indicate a pro-oxidant imbalance in SSc, likely related to systemic inflammation and endothelial injury. However, extensive prospective studies are needed to verify whether it is also associated with clinical disease progression.
