Compounds in sand fly saliva elicit specific immune responses that may play a role in the establishment of canine Leishmania infection. Although canine antibodies to anti-sand fly saliva antigens have been extensively studied, little is known about cellular immune responses against Phlebotomus perniciosus salivary proteins. This study aimed to explore humoral and T-cell-mediated immunity against P. perniciosus salivary proteins in dogs (n = 85) from Mallorca (Spain), a leishmaniosis-endemic area, and find correlations with demographic (age, sex, and breed) and parasite-specific immunological parameters. Anti-sand fly saliva IgG was examined using a P. perniciosus whole salivary gland homogenate (SGH) ELISA and recombinant salivary protein rSP03B ELISA. Interferon gamma (IFN-γ) release whole blood assays with L. infantum soluble antigen (LSA), SGH, and rSP03B were also performed. Positive correlations were found between IgG levels in the SGH and rSP03B tests and between concentrations of SGH IFN-γ and rSP03B IFN-γ. While concentrations of SGH IFN-γ and rSP03B IFN-γ were low and produced only by a minority of dogs (less than 20%), high levels and frequencies of LSA IFN-γ as well as anti-saliva IgG for SGH and rSP03B were detected in a majority of dogs (61% and 75%, respectively). LSA IFN-γ levels were positively correlated with age and Leishmania-specific antibodies. In conclusion, dogs from a leishmaniosis-endemic area presented high humoral immunity against P. perniciosus salivary proteins, but their cellular immunity to these proteins was low and less frequent.

• MeSH
• buněčná imunita * MeSH
• endemické nemoci MeSH
• hmyzí proteiny * imunologie   MeSH
• humorální imunita * MeSH
• imunoglobulin G krev   imunologie   MeSH
• interferon gama MeSH
• leishmanióza * imunologie   veterinární   epidemiologie   MeSH
• nemoci psů * imunologie   parazitologie   epidemiologie   MeSH
• Phlebotomus * imunologie   MeSH
• psi MeSH
• slinné proteiny a peptidy * imunologie   MeSH
• T-lymfocyty * imunologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• psi MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Španělsko MeSH

INTRODUCTION: The immunosuppressive roles of galectin-3 (Gal-3) in carcinogenesis make this lectin an attractive target for pharmacological inhibition in immunotherapy. Although current clinical immunotherapies appear promising in the treatment of solid tumors, their efficacy is significantly weakened by the hostile immunosuppressive tumor microenvironment (TME). Gal-3, a prominent TME modulator, efficiently subverts the elimination of cancer, either directly by inducing apoptosis of immune cells or indirectly by binding essential effector molecules, such as interferon-gamma (IFNγ). METHODS: N-(2-Hydroxypropyl)methacrylamide (HPMA)-based glycopolymers bearing poly-N-acetyllactosamine-derived tetrasaccharide ligands of Gal-3 were designed, synthesized, and characterized using high-performance liquid chromatography, dynamic light scattering, UV-Vis spectrophotometry, gel permeation chromatography, nuclear magnetic resonance, high-resolution mass spectrometry and CCK-8 assay for evaluation of glycopolymer non-toxicity. Pro-immunogenic effects of purified glycopolymers were tested by apoptotic assay using flow cytometry, competitive ELISA, and in vitro cell-free INFγ-based assay. RESULTS: All tested glycopolymers completely inhibited Gal-3-induced apoptosis of monocytes/macrophages, of which the M1 subtype is responsible for eliminating cancer cells during immunotherapy. Moreover, the glycopolymers suppressed Gal-3-induced capture of glycosylated IFNγ by competitive inhibition to Gal-3 carbohydrate recognition domain (CRD), which enables further inherent biological activities of this effector, such as differentiation of monocytes into M1 macrophages and repolarization of M2-macrophages to the M1 state. CONCLUSION: The prepared glycopolymers are promising inhibitors of Gal-3 and may serve as important supportive anti-cancer nanosystems enabling the infiltration of proinflammatory macrophages and the reprogramming of unwanted M2 macrophages into the M1 subtype.

• MeSH
• akrylamidy chemie   farmakologie   MeSH
• apoptóza účinky léků   MeSH
• galektin 3 * antagonisté a inhibitory   MeSH
• galektiny MeSH
• interferon gama * metabolismus   MeSH
• krevní proteiny MeSH
• lidé MeSH
• makrofágy účinky léků   MeSH
• monocyty * účinky léků   MeSH
• nádorové mikroprostředí účinky léků   MeSH
• polymery * chemie   farmakologie   MeSH
• protinádorové látky * farmakologie   chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Interferon‐induced transmembrane proteins (IFITMs) are frequently overexpressed in cancer cells, including cervical carcinoma cells, and play a role in the progression of various cancer types. However, their mechanisms of action remain incompletely understood. In the present study, by employing a combination of surface membrane protein isolation and quantitative mass spectrometry, it was comprehensively described how the IFITM1 protein influences the composition of the cervical cancer cell surfaceome. Additionally, the effects of interferon‐γ on protein expression and cell surface exposure were evaluated in the presence and absence of IFITM1. The IFITM1‐regulated membrane and membrane‐associated proteins identified are involved mainly in processes such as endocytosis and lysosomal transport, cell‐cell and cell‐extracellular matrix adhesion, antigen presentation and the immune response. To complement the proteomic data, gene expression was analyzed using reverse transcription‐quantitative PCR to distinguish whether the observed changes in protein levels were attributable to transcriptional regulation or differential protein dynamics. Furthermore, the proteomic and gene expression data are supported by functional studies demonstrating the impact of the IFITM1 and IFITM3 proteins on the adhesive, migratory and invasive capabilities of cervical cancer cells, as well as their interactions with immune cells.

• MeSH
• buněčná adheze MeSH
• diferenciační antigeny * metabolismus   genetika   MeSH
• fenotyp MeSH
• interferon gama farmakologie   metabolismus   MeSH
• lidé MeSH
• membránové proteiny * metabolismus   genetika   MeSH
• nádorové buněčné linie MeSH
• nádory děložního čípku * patologie   genetika   metabolismus   imunologie   MeSH
• pohyb buněk MeSH
• proteiny vázající RNA * metabolismus   genetika   MeSH
• proteom * MeSH
• proteomika metody   MeSH
• regulace genové exprese u nádorů MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Cytokine licensing with pro-inflammatory molecules, such as tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), has emerged as a promising strategy to enhance the therapeutic potential of multipotent mesenchymal stromal cells (MSCs). While licensing has demonstrated benefits for immunomodulation, its effects on other key MSC functions, including differentiation and paracrine activity, remain incompletely explored. In this study, we evaluated the transcriptomic, metabolomic, and functional changes induced by short-term TNF-α/IFN-γ priming of Wharton's jelly-derived MSCs (WJ-MSCs). METHODS: WJ-MSCs were expanded and exposed to TNF-α and IFN-γ (10 ng/ml each) for 24 h. Transcriptomic analysis was performed using RNA sequencing to identify differentially expressed genes related to immune modulation and lineage commitment. Metabolomic profiling was conducted using high-resolution mass spectrometry to assess changes in metabolic pathways. Functional assays evaluated the effects of cytokine priming on induced differentiation and growth factor secretion. RESULTS: Cytokine licensing induced notable alterations in gene expression, upregulating pathways linked to immune response, inflammation, and cytokine signalling. However, short-term cytokine treatment significantly attenuated the osteogenic and adipogenic differentiation of MSCs, as evidenced by the reduced expression of RUNX2, ALP, CEBPA, and PPARG. The priming had a negligible effect on EGF, FGF-2, HGF, LIF, and SCF secretion. The production of VEGF-A and VEGF-C was elevated, although the levels remained low. Metabolomic analysis revealed enhanced kynurenine pathway activity, indicative of increased tryptophan catabolism, accompanied by elevated levels of fatty acids and polyamines. CONCLUSIONS: Our findings demonstrate that TNF-α/IFN-γ priming reprograms WJ-MSCs by enhancing their immunomodulatory capacity at the expense of differentiation potential. These results highlight the need for tailored strategies to optimize MSC functionality for specific clinical applications.

• MeSH
• buněčná diferenciace * účinky léků   MeSH
• cytokiny * farmakologie   MeSH
• imunomodulace * účinky léků   MeSH
• interferon gama * farmakologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• mezenchymální kmenové buňky * metabolismus   cytologie   účinky léků   imunologie   MeSH
• TNF-alfa * farmakologie   MeSH
• Whartonův rosol * cytologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Trained immunity is defined as an enhanced state of the innate system which leads to an improved immune response against related or non-related pathogens. Bacillus Calmette-Guérin (BCG) vaccine, a live attenuated Mycobacterium bovis strain, is currently one of the main inductors of trained immunity. The objective of the present study was to evaluate the protective effects of heat-inactivated M. bovis (HIMB) against Plasmodium berghei and Borrelia burgdorferi and characterize the immunological mechanisms involved. BALB/c and C3H/HeN mice were randomly assigned in similar number to either immunized group receiving two oral doses of HIMB with a 4-week interval, or control group treated with PBS. All the BALB/c mice were intraperitoneally infected with P. berghei while the C3H/HeN mice were subcutaneously infected with B. burgdorferi. Pathogen burden was significantly reduced in both immunized groups when compared to controls. The number of macrophages significantly decreased in the liver or in the spleen of the mice that had been immunized prior to the challenge with P. berghei or B. burgdorferi, respectively. Furthermore, the immunized groups showed an apparent upregulation of IFN-γ, TNF-α and IL-1α in the liver (P. berghei challenge) or a significant increase in IL-1α producing cells in the spleen (B. burgdorferi challenge). Our findings suggest that oral immunization with heat-inactivated mycobacteria limits pathogen burden through stimulation of the innate immune response in two vector-borne diseases in mice.

• MeSH
• adjuvancia imunologická * aplikace a dávkování   MeSH
• BCG vakcína * imunologie   aplikace a dávkování   MeSH
• Borrelia burgdorferi imunologie   MeSH
• cytokiny MeSH
• inaktivované vakcíny imunologie   aplikace a dávkování   MeSH
• interferon gama imunologie   MeSH
• interleukin-1alfa imunologie   MeSH
• játra imunologie   MeSH
• lymeská nemoc * prevence a kontrola   imunologie   MeSH
• makrofágy imunologie   MeSH
• malárie * prevence a kontrola   imunologie   MeSH
• Mycobacterium bovis * imunologie   MeSH
• myši inbrední BALB C MeSH
• myši inbrední C3H MeSH
• myši MeSH
• Plasmodium berghei imunologie   MeSH
• protilátky bakteriální krev   MeSH
• slezina imunologie   mikrobiologie   MeSH
• TNF-alfa imunologie   MeSH
• vysoká teplota MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Screening for tuberculosis infections (TBI) using the tuberculin skin test or interferon-gamma release assays (IGRA) is crucial in controlling the global TB burden. This study evaluates the performance of a new IGRA for the detection of T-cell responses against Mycobacterium tuberculosis. Blood samples from 34 adults with tuberculosis disease (TB) and from 30 children with TB, TBI or without TB were analyzed using the prototype Quan-T-Cell TB (EUROIMMUN). The pediatric samples were additionally measured using the established QuantiFERON-TB Gold Plus assay (Qiagen). Clinical performance and inter-assay concordance were analyzed. The prototype Quan-T-Cell TB yielded positivity rates of 88.2% and 100% in adults with TB and children with TBI, respectively, at a specificity of 93.8%. Comparison between the two IGRAs showed positive, negative and overall agreement rates of 100%, 93.8% and 96.3%, respectively, with a kappa score of 0.924 indicating almost perfect agreement. Our study shows promising results of the new prototype Quan-T-Cell TB, as reflected by high concordance with the final diagnosis in adults and children and performance comparable to that of the QuantiFERON IGRA. In individual cases, the data suggest that the prototype Quan-T-Cell TB may be even more consistent with TBI-related clinical findings. Unlike the QuantiFERON assay, the Quan-T-Cell TB has a predefined borderline range, which is advantageous as it may help to differentiate non-specific variation near the cut-off, and fewer sample tubes are required per analysis. The new Quan-T-Cell TB may therefore be a good alternative to the established QuantiFERON IGRA for TBI screening. Further assay optimization is underway, including evaluation studies based on larger patient and control cohorts.

• MeSH
• dítě MeSH
• dospělí MeSH
• interferon gama MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Mycobacterium tuberculosis * imunologie   MeSH
• předškolní dítě MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• T-lymfocyty * imunologie   MeSH
• test pomocí interferonu gama * metody   MeSH
• tuberkulóza * diagnóza   imunologie   mikrobiologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH

BACKGROUND: Cognitive impairment is a well-recognized symptom of multiple sclerosis (MS) that can manifest early in the disease course. Deficits in cognitive function can have a major impact on daily life. However, cognitive decline is often under-examined in clinical trials and clinical practice due to lack of adequate data. The objective of this study was to examine the longitudinal effect of ocrelizumab vs interferon beta (IFNβ)-1a on cognitive impairment in 2 phase 3 studies in relapsing MS (RMS). METHODS: The pooled population of participants with RMS (n = 1656) from the OPERA I/II clinical trials received subcutaneous IFNβ-1a (44 μg; n = 829) 3 times weekly or intravenous ocrelizumab (600 mg; n = 827) every 24 weeks. Cognition was assessed with a Symbol Digit Modalities Test (SDMT), administered in written or oral form according to each site investigator's choice, that primarily measured cognitive processing speed at baseline and every 12 weeks until the end of the double-blind treatment (96 weeks). Treatment effects were investigated based on longitudinal linear models for the change from baseline in SDMT and Cox regression for the time to 12- or 24-week confirmed decline of ≥4 points. RESULTS: Among the participants with an SDMT assessment at baseline and ≥1 postbaseline time point (IFNβ-1a, n = 749; ocrelizumab, n = 766), ocrelizumab treatment was associated with a greater mean SDMT improvement over 96 weeks than IFNβ-1a treatment (5.4 [95 % CI, 4.4-6.5] vs 4.0 [95 % CI, 3.0-5.1]; adjusted mean difference, 1.4 [95 % CI, 0.05-2.72]; P = 0.042). The risk of a clinically meaningful SDMT decline (≥4 points) was lower for those treated with ocrelizumab for both ≥12 weeks (IFNβ-1a, 18.4 %; ocrelizumab, 12.7 %; hazard ratio, 0.63 [95 % CI, 0.47-0.85]; P = 0.003) and ≥24 weeks (IFNβ-1a, 12.9 %; ocrelizumab, 7.9 %; HR, 0.57 [95 % CI, 0.39-0.82]; P = 0.003). CONCLUSION: Ocrelizumab treatment resulted in better cognitive outcomes as measured by SDMT in participants with RMS compared with IFNβ-1a treatment. However, methodological limitations need to be considered when interpreting these data. CLINICALTRIALS: gov: NCT01247324, NCT01412333.

• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• humanizované monoklonální protilátky * aplikace a dávkování   farmakologie   škodlivé účinky   MeSH
• imunologické faktory * aplikace a dávkování   škodlivé účinky   farmakologie   MeSH
• interferon beta 1a * aplikace a dávkování   farmakologie   MeSH
• kognitivní dysfunkce etiologie   farmakoterapie   chemicky indukované   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• relabující-remitující roztroušená skleróza * farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

BACKGROUND AND OBJECTIVES: Patients with multiple sclerosis (MS) may demonstrate better disease control when treatment is initiated on high-efficacy disease-modifying therapies (DMTs) from onset. This subgroup analysis assessed the long-term efficacy and safety profile of the high-efficacy DMT ocrelizumab (OCR) as first-line therapy for early-stage relapsing MS (RMS). METHODS: Post hoc exploratory analyses of efficacy and safety were performed in a subgroup of treatment-naive patients with RMS who received ≥1 dose of OCR in the multicenter OPERA I/II (NCT01247324/NCT01412333) studies. Patients were randomized to OCR or interferon β-1a for 96 weeks (double-blind controlled treatment period [DBP]), before switching to OCR in the open-label extension (OLE). Efficacy assessments included no evidence of disease activity (NEDA-3), 24-week confirmed disability progression (CDP), MRI lesion activity, change in whole-brain volume; with safety outcomes assessed over a 9-year treatment period. RESULTS: Overall, 757 patients were included (interferon-treated n = 382, mean age 36.3 years, 65.7% female; OCR-treated n = 375, mean age 35.5 years, 64.0% female); 505 of 757 (66.7%) completed 9 years of follow-up. The difference in NEDA status between OCR-treated and interferon-treated patients achieved during the DBP (72.5% and 43.8%, respectively, odds ratio 3.48, 95% CI 2.52-4.81) was maintained throughout the 7-year OLE (48.2% vs 25.7%; odds ratio 2.72, 95% CI 1.94-3.82). No 24-week CDP was observed in 78.7% of OCR-treated patients over 9 years. Brain volume loss over the entire study period remained numerically higher among patients starting OCR later (p = 0.09 at OLE at week 336). During the DBP, safety profiles in both groups were similar; no new safety signals were observed during the OLE. Over >9 years of continuous OCR treatment, the rate of infections remained low and stable over time. DISCUSSION: A higher proportion of OCR-treated patients achieved NEDA status compared with interferon-treated patients during the DBP, which was maintained throughout the OLE. After switching to OCR, disability accrual and brain volume loss among interferon-treated patients became similar to the OCR-OCR group, but disability and brain volume loss accrued during interferon treatment were not recovered. Possible study limitations include assessment bias due to unmaintained blinding during the OLE. These data support OCR as first-line therapy for these patients. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that OCR delays disease progression in treatment-naïve patients with early-stage RMS.

• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• humanizované monoklonální protilátky * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• imunologické faktory * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• interferon beta 1a terapeutické užití   aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• progrese nemoci MeSH
• relabující-remitující roztroušená skleróza * farmakoterapie   diagnostické zobrazování   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: The longitudinal study was conducted over the initial 2 years of the COVID-19 pandemic, spanning from June 2020 to December 2022, in healthcare workers (HCWs) of the Thomayer University Hospital. A total of 3892 blood samples were collected and analyzed for total nucleocapsid (N) antibodies. The aim of the study was to evaluate the dynamics of N antibodies, their relationship to the PCR test, spike (S) antibodies, interferon-gamma, and prediction of reinfection with SARS-CoV-2. METHODS: Blood collections were performed in three rounds, along with questionnaires addressing clinical symptoms of past infection, PCR testing, and vaccination. Antibody measurements included total N antibodies (Roche Diagnostics) and postvaccination S antibodies (Euroimmun). Cellular immunity was tested by interferon-gamma release assay (Euroimmun). RESULTS: At the end of the study, 35.9% of HCWs were positive for N antibodies, and 39.5% of HCWs had either known PCR positivity or N antibodies or both. Ten percent of participants had no knowledge of a COVID-19 infection and 35% of positive individuals exhibited no symptoms. The values of positive antibodies decrease over a period of 6 months to 1 year, depending on the initial value, and their dynamics are highly variable. The study also demonstrated that the highest levels of spike antibodies and interferon-gamma occur during so-called hybrid immunity. CONCLUSION: Nucleocapsid antibodies proved valuable in monitoring SARS-CoV-2 infection dynamics, and they may detect cases of SARS-CoV-2 infection missed by PCR tests. The study identified distinct patterns in antibody dynamics and protection of hybrid immunity during reinfection.

• MeSH
• biologické markery krev   MeSH
• COVID-19 * imunologie   krev   diagnóza   epidemiologie   MeSH
• dospělí MeSH
• fosfoproteiny MeSH
• glykoprotein S, koronavirus imunologie   MeSH
• interferon gama krev   MeSH
• koronavirové nukleokapsidové proteiny imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• nemocnice univerzitní MeSH
• nukleokapsida imunologie   MeSH
• protilátky virové * krev   MeSH
• SARS-CoV-2 * imunologie   MeSH
• sérologické testování na COVID-19 metody   MeSH
• zdravotnický personál * statistika a číselné údaje   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Účinnost interferonu alfa v terapii Ph negativních myeloproliferativních onemocnění je známá již několik desetiletí, nicméně až nové pegylované formy s lepšími farmakokinetickými vlastnostmi vedly k jeho rozšíření do běžné klinické praxe. Interferon alfa prokazatelně vede u vysokého procenta nemocných s pravou polycytemií k dosažení nejenom hematologické, ale i molekulární odpovědi a tím snižuje riziko přechodu do myelofibrózy. Jednotlivé přípravky pegylovaných interferonů se od sebe liší způsobem pegylace, což má za následek rozdíly nejenom v četnosti frekvence aplikace, ale také v toleranci léčby.

Efficiency of interferon alpha in treatment of Ph-negative myeloproliferative neoplasms is well known for many decades, however only recently new pegylated forms of interferon with better pharmacokinetic profile led to its widespread use in routine clinical practice. Interferon alpha has shown in multiple studies in substantial proportion of patients with polycythemia vera its potential to achieve not only hematological but also molecular response important for reducing risk of progression to myelofibrosis. In the Czech Republic, there are two pegylated interferon forms with different pegylation, which causes differences in dosing intervals and safety profile.

• Klíčová slova
• Ropeg-IFN, Peg-IFN,
• MeSH
• interferon alfa * farmakologie   klasifikace   terapeutické užití   MeSH
• lidé MeSH
• nežádoucí účinky léčiv MeSH
• polycythaemia vera * diagnóza   farmakoterapie   MeSH
• tolerance léku MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH