The search for biological markers, which allow a relatively accurate assessment of the individual course of pulmonary sarcoidosis at the time of diagnosis remains one of the research priorities in this field of pulmonary medicine. The aim of our study was to investigate possible prognostic factors for pulmonary sarcoidosis with a special focus on cellular immune inflammation markers. 2 years follow-up of the study population after initial prospective and simultaneous analysis of lymphocyte activation markers expression in the blood, as well as bronchoalveolar lavage fluid (BALF), and lung biopsy tissue of patients with newly diagnosed pulmonary sarcoidosis, was done. We found that some blood and BAL fluid immunological markers and lung computed tomography (CT) patterns have been associated with a different course of sarcoidosis. We revealed five markers that had a significant negative association with the course of sarcoidosis (worsening pulmonary function tests and/or the chest CT changes) – blood CD4+CD31+ and CD4+CD44+ T lymphocytes, BALF CD8+CD31+ and CD8+CD103+ T lymphocytes and a number of lung nodules on chest CT at the time of the diagnosis. Cut-off values, sensitivity, specificity, and odds ratio for predictors of sarcoidosis progression were calculated. These markers may be reasonable predictors of sarcoidosis progression.
Radvilė Malickaitė1,2, Aldona Stanevičienė2, Kęstutis Ručinskas1,2, Laimutė Jurgauskienė1,2, Saulius Miniauskas1,2, Vytautas Sirvydis1,21 Vilniaus universiteto Širdies ir kraujagyslių ligų klinikos Širdies chirurgijos centras,Santariškių g. 2, LT-08661 Vilnius2 Vilniaus universiteto ligoninės Santariškių klinikos, Santariškių g. 2, LT-08661 VilniusEl paštas: radvile.malickaite@santa.lt Tikslas Įvertinti Vilniaus universiteto ligoninės Santariškių klinikų Širdies chirurgijos centre atliekamos dirbtinės širdies implantavimo procedūros įtaką imuninei širdies laukiančių recipientų būklei ir palyginti gautus rezultatus su kitų centrų duomenimis. Ligoniai ir metodai Ištirta aštuonių potencialių širdies recipientų, kurių kraujotaka buvo palaikoma dirbtinės širdies skilvelio (DŠS), imuninių rodiklių dinamika: prieš DŠS implantavimą ir praėjus ne mažiau kaip vienam mėnesiui po operacijos. Nustatytas periferinio kraujo imunokompetentinių ląstelių CD3+CD4+ ir CD3+CD8+ skaičius, Apo-1/FAS (CD95) ekspresija CD4+ ir CD8+ limfocitų paviršiuje, viduląstelinė aktyvi kaspazė-3 ir sensitizacija HLA antigenams. Rezultatai Po DŠS prijungimo atsiranda limfocitų T helperių (CD3+CD4+) skaičiaus trūkumas, ryškesnis pacientų, kuriems implantuotas išorinis dirbtinis skilvelis. Numanomas ląstelių praradimo mechanizmas yra apoptozės indukcija. Nepaisant ilgalaikio DŠS prijungimo ir pakartotinių kraujo produktų perpylimų (lentelė), antikūnai prieš HLA sistemos antigenus daugumai pacientų nesigamino: sensitizacija nustatyta tik dviem iš aštuonių pacientų (gavusių santykiškai daugiau kraujo produktų). Išvada Sensitizacija apsunkina pacientų gydymą, ypač vengtini kraujo produktai. Patartina naudoti leukofiltruotus kraujo produktus. Pagrindiniai žodžiai: dirbtiniai širdies skilveliai, imunologinė sensitizacija, apoptozė Comparison of quality of life and physical condition of heart failure Radvilė Malickaitė1,2, Aldona Stanevičienė2, Kęstutis Ručinskas1,2, Laimutė Jurgauskienė1,2, Saulius Miniauskas1,2, Vytautas Sirvydis1,21 Vilnius University Clinic of Cardiovascular Diseases, Cardiac Surgery Centre,Santariškių str. 2, LT-08661 Vilnius, Lithuania2 Vilnius University Hospital „Santariškių klinikos“, Santariškių str. 2, LT-08661 Vilnius, LithuaniaE-mail: radvile.malickaite@santa.lt Objective This study was designed to characterize alterations in the immune system of patients who received artificial heart (AH) placement therapy for end-stage heart failure as a bridge to heart transplantation at the Vilnius University Cardial Surgery Centre. Patients and methods Immunological studies were performed in 8 pts awaiting cardiac transplantation with AH assist (7 of them were transplanted after 75–1050 days of support). Immunological indices before AH placement and after one month of mechanical assistance (period free from infection) were compared. Fluorochrome-labeled Mabs were used for immunophenotypic analysis of circulating T cells and apoptocic activity evaluation. Antibodies against HLA class I molecules were detected by a standard microlymphocytotoxic test. Results AH recipients showed relative lymphopenia, reduction in CD4 T cell counts, a decreased CD+4+ / CD8+ ratio. Six of the eight recipients with long-term support did not produce HLA antibodies despite receiving blood products during support. Conclusions In conclusion, these results suggest that reduction in CD4+ T cell levels accompanying AH support may increase the prevalence of infectious complications and HLA sensitization. Key words: heart-assist devices, immune, sensitization, apoptosis
Background and Objectives: Severe and critical COVID-19 pneumonia can lead to long-term complications, especially affecting pulmonary function and immune health. However, the extent and progression of these complications over time are not well understood. This study aimed to assess lung function, radiological changes, and some immune parameters in survivors of severe and critical COVID-19 up to 12 months after hospital discharge. Materials and Methods: This prospective observational cohort study followed 85 adult patients who were hospitalized with severe or critical COVID-19 pneumonia at a tertiary care hospital in Vilnius, Lithuania, for 12 months post-discharge. Pulmonary function tests (PFTs), including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and diffusion capacity for carbon monoxide (DLCO), were conducted at 3, 6, and 12 months. High-resolution chest computed tomography (CT) scans assessed residual inflammatory and profibrotic/fibrotic abnormalities. Lymphocyte subpopulations were evaluated via flow cytometry during follow-up visits to monitor immune status. Results: The median age of the cohort was 59 years (IQR: 51–64). Fifty-three (62.4%) patients had critical COVID-19 disease. Pulmonary function improved significantly over time, with increases in FVC, FEV1, VC, TLC, and DLCO. Residual volume (RV) did not change significantly over time, suggesting that some aspects of lung function, such as air trapping, remained stable and may require attention in follow-up care. The percentage of patients with restrictive spirometry patterns decreased from 24.71% at 3 months to 14.8% at 12 months (p < 0.05). Residual inflammatory changes on CT were present in 77.63% at 6 months, decreasing to 69.62% at 12 months (p < 0.001). Profibrotic changes remained prevalent, affecting 82.89% of patients at 6 months and 73.08% at 12 months. Lymphocyte counts declined significantly from 3 to 12 months (2077 cells/µL vs. 1845 cells/µL, p = 0.034), with notable reductions in CD3+ (p = 0.040), CD8+ (p = 0.007), and activated CD3HLA-DR+ cells (p < 0.001). This study found that higher CD4+ T cell counts were associated with worse lung function, particularly reduced total lung capacity (TLC), while higher CD8+ T cell levels were linked to improved pulmonary outcomes, such as increased forced vital capacity (FVC) and vital capacity (VC). Multivariable regression analyses revealed that increased levels of CD4+/CD28+/CD192+ T cells were associated with worsening lung function, while higher CD8+/CD28+/CD192+ T cell counts were linked to better pulmonary outcomes, indicating that immune dysregulation plays a critical role in long-term respiratory recovery. Conclusions: Survivors of severe and critical COVID-19 pneumonia continue to experience significant long-term impairments in lung function and immune system health. Regular monitoring of pulmonary function, radiological changes, and immune parameters is essential for guiding personalized post-COVID-19 care and improving long-term outcomes. Further research is needed to explore the mechanisms behind these complications and to develop targeted interventions for long COVID-19.
Many theories have been proposed to explain pathogenesis of COPD; however, remains unclear why the majority of smokers (~80%) do not develop COPD, or only develop a mild disease. To explore if COPD has an autoimmune component, the role of T regulatory lymphocytes (Tregs) in the lung tissue of COPD patients is of crucial importance.Bronchial tissue biopsy samples were prospectively collected from 64 patients (39 COPD and 25 controls - 15 smokers and 10 non-smokers). The patients with COPD were subdivided into mild/moderate (GOLD stage I-II) and severe/very severe (GOLD stage III-IV) groups. Digital image analysis was performed to estimate densities of CD4+ CD25+ cell infiltrates in double immunohistochemistry slides of the biopsy samples. Blood samples were collected from 42 patients (23 COPD and 19 controls) and tested for CD3+ CD4+ CD25+ bright lymphocytes by flow cytometry.The number of intraepithelial CD4+ CD25+ lymphocytes mm-2 epithelium was significantly lower in the severe/very severe COPD (GOLD III-IV) group as well as in the control non-smokers (NS) group (p < 0,0001). Likewise, the absolute number of Treg (CD3+ CD4+ CD25+ bright) cells in the peripheral blood samples was significantly different between the four groups (p = 0.032). The lowest quantity of Treg cells was detected in the severe/very severe COPD and healthy non-smokers groups.Our findings suggest that severe COPD is associated with lower levels of Tregs in the blood and bronchial mucosa, while higher Tregs levels in the smokers without COPD indicate potential protective effect of Tregs against developing COPD.
Background. Cardiac surgery provokes an intense inflammatory response that can cause an immunosuppressive state and adverse postoperative outcomes. We recently showed that postoperative immunonutrition with glutamine in “fragile” low-risk cardiac surgery patients was associated with a significantly increased level of CD3+ and CD4+ T cells. In order to clarify the biological relevance and clinical importance of these findings, we investigated whether an increase in the CD4+ T cell level was caused by changes in the systemic inflammatory response (caused by surgery or infection) and if it was associated with their activation status.Methods. A randomized control study of low operative risk but “fragile” cardiac surgery patients was performed. Patients were randomized into immunonutrition (IN) and control groups (C). The IN group received normal daily meals plus special immune nutrients for 5 days postoperatively, while the C group received only normal daily meals. Laboratory parameters were investigated before surgery and on the sixth postoperative day and the groups were compared accordingly. The expression of the CD69+ marker was investigated to determine T cell activation status. Serum concentrations of cytokines (interleukin-10 (IL-10), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6)) and C-reactive protein (CRP) were determined to assess the systemic inflammatory response, while procalcitonin (PCT) levels were evaluated to confirm or deny possible bacterial infection.Results. Fifty-five patients were enrolled in the study. Twenty-seven (49.1%) were randomized in the IN group. Results show that on the sixth postoperative day, the CD4+CD69+ and CD8+CD69+ counts did not differ between the IN and C groups, accordingly 0.25 [0.16–0.50] vs 0.22 [0.13-0.41], p=0.578 and 0.13 [0.06–0.3] vs 0.09 [0.05–0.14], p=0.178. Also, statistically significant differences were not observed in the cytokine levels (IN and C groups: TNF-α 8.13 [7.32–10.31] vs 8.78 [7.65–11.2], p=0.300; IL-6 14.65 [9.28–18.95] vs 12.25 [8.55–22.50], p=0.786; IL-10 5.0 [5.0–5.0] vs 5.0 [5.0–5.0], p=0.343 respectively), which imply that an elevated T cell count is not associated with the systemic inflammatory response. Also, PCT (IN and C groups: 0.03 [0.01–0.09] vs 0.05 [0.03–0.08], p=0.352) and CRP (IN and C groups 62.7 [34.2–106.0] vs 63.7 [32.9–91.0], p=0.840) levels did not differ between the two groups. Moreover, low levels of PCT indicated that the increase in T cell count was not determined by bacterial infection.Conclusions. Our findings showed that CD4+ T cell levels were associated with neither the systemic inflammatory response nor bacterial infection. Secondly, increases in T cells are not accompanied by their activation status. These results suggest a hypothesis that a higher postoperative T cell concentration may be associated with postoperative immunonutrition in low-risk cardiac surgery patients with intact cellular vitality, i.e. “fragile”. However, immunonutrition alone did not affect T cell activation status.
Background/Aim: Severe pulmonary influenza A virus (IAV) infection causes lung inflammation and expression of inducible nitric oxide synthase (iNOS), leading to overproduction of nitric oxide (NO). We studied whether zanamivir reduces pulmonary inflammation through inhibition of NO production in mice. Materials and Methods: We treated IAV-infected mice daily with intranasal zanamivir. Controls were infected and either placebo-treated or untreated, or not infected and placebo-treated. Mice were weighed daily. After euthanasia on day 3, lungs were excised and bronchoalveolar lavage was performed and fluid nitrite concentration was determined. Lungs were analyzed microscopically. iNOS and IAV RNA levels in lungs were assessed using quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Results: Mice undergoing zanamivir treatment had less weight loss, viral replication, and lung damage, as well as significant reductions of local NO and iNOS mRNA synthesis (p<0.05). Conclusion: Zanamivir is associated with an anti-inflammatory effect mediated through inhibition of NO production in IAV-infected mice.
The aim of the study. To evaluate the count of regulatory T lymphocytes (CD4+CD25+), as cells, possibly decreasing inflammation, in the patients suffering from different severity COPD and compare with the healthy subjects. Materials and methods. CD4+CD25+ and CD4+CD25+ bright blood cells were examined for 43 COPD patients and 26 healthy persons. The control group consisted of smokers and non smokers. In accordance with spirometrical severity of the disease COPD patients were distributed into two groups: a group (I) of patients with mild and moderate obstruction and group (II) consisted of patients with severe and very severe obstruction. Results. The comparison of COPD and control groups demonstrated no statistically significant difference either in total number of CD4+CD25+ cells, or in CD4+CD25+ bright (Treg). However, in the group of patients with severe and very severe COPD, the count of CD4+CD25+ and CD4+CD25+ bright cells was found to be significantly lower, in comparison with healthy smokers (376±235 vs 610±217 p = 0.01 and 47±26 vs 75±27, p = 0.03).The difference between smoking and non-smoking controls was found to be statistically significant, also: CD4+CD25+ and CD4+CD25+ bright lymphocytes was markedly higher in healthy smokers than in non-smokers (610±217 vs 392±157, p = 0.02 and 59±29 vs 42±19, p = 0.03). Conclusion. Our results confirmed the proposition that the dysfunction of immune system plays the role in development of COPD. Inflammation of the airways during COPD may be supressed inadequately due to insufficiency of CD4+CD25+ (T regulatory) lymphocytes.
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