The existence of eosinophils was documented histopathologically in the first half of the 19th century. However, the term "eosinophils" was first used by Paul Ehrlich in 1878. Since their discovery and description, their existence has been associated with asthma, allergies, and antihelminthic immunity. Eosinophils may also be responsible for various possible tissue pathologies in many eosinophil-associated diseases. Since the beginning of the 21st century, the understanding of the nature of this cell population has undergone a fundamental reassessment, and in 2010, J. J. Lee proposed the concept of "LIAR" (Local Immunity And/or Remodeling/Repair), underlining the extensive immunoregulatory functions of eosinophils in the context of health and disease. It soon became apparent that mature eosinophils (in line with previous morphological studies) are not structurally, functionally, or immunologically homogeneous cell populations. On the contrary, these cells form subtypes characterized by their further development, immunophenotype, sensitivity to growth factors, localization, role and fate in tissues, and contribution to the pathogenesis of various diseases, including asthma. The eosinophil subsets were recently characterized as resident (rEos) and inflammatory (iEos) eosinophils. During the last 20 years, the biological therapy of eosinophil diseases, including asthma, has been significantly revolutionized. Treatment management has been improved through the enhancement of treatment effectiveness and a decrease in the adverse events associated with the formerly ultimately used systemic corticosteroids. However, as we observed from real-life data, the global treatment efficacy is still far from optimal. A fundamental condition, "sine qua non", for correct treatment management is a thorough evaluation of the inflammatory phenotype of the disease. We believe that a better understanding of eosinophils would lead to more precise diagnostics and classification of asthma subtypes, which could further improve treatment outcomes. The currently validated asthma biomarkers (eosinophil count, production of NO in exhaled breath, and IgE synthesis) are insufficient to unveil super-responders among all severe asthma patients and thus give only a blurred picture of the adepts for treatment. We propose an emerging approach consisting of a more precise characterization of pathogenic eosinophils in terms of the definition of their functional status or subset affiliation by flow cytometry. We believe that the effort to find new eosinophil-associated biomarkers and their rational use in treatment algorithms may ameliorate the response rate to biological therapy in patients with severe asthma.
- MeSH
- Hypersensitivity * metabolism MeSH
- Biomarkers metabolism MeSH
- Asthma * drug therapy MeSH
- Eosinophils metabolism MeSH
- Humans MeSH
- Leukocyte Count MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Nepřímý imunofluorescenční mikroskopický průkaz autoprotilátek patří mezi nosné metody imunologické laboratorní diagnostiky. Jsou nezbytné pro diagnostiku a monitorování autoimunitních, imunopatologických onemocnění. Výsledky těchto metod jsou velmi závislé na zkušenostech hodnotitele. Běžně se hodnotitelé střídají nebo je třeba zacvičit nového pracovníka. V těchto případech je kontinuita nálezů ohrožena. Z tohoto důvodu je žádoucí shodu mezi hodnotiteli ověřovat. Cílem této studie bylo prověřit shodu mezi třemi hodnotiteli imunofluorescenčních nálezů. V období čtyř měsíců bylo hodnoceno 163 vzorků pro stanovení přítomnosti protilátek proti antigenům cytoplasmatických granulí neutrofilů ANCA, 301 vzorků pro stanovení protilátek proti endomysiu a 772 vzorků protilátek proti jaderným antigenům ANA. Pro posouzení shody mezi hodnotiteli bylo použito Cohenovo kappa (κ) nebo vážené Cohenovo kappa (κwlin ) a shoda byla vyjádřena v procentech. V souhrnu lze shodu mezi sledovanými hodnotiteli označit jako dobrou. U kvalitativního srovnání (pozitivní/negativní) se hodnota κ pohybovala od 0,79 až po 1,00. U kvantitativního hodnocení metod byla nejmenší shoda, vyjádřena hodnotou κ wlin , zjištěna u ANA 0,82 a nejlepší u ANCA 0,98. Největší rozdíly byly pozorovány u rozlišení fluorescenčních obrazů ANA a ANCA. Tady se hodnoty κ pohybovaly od 0,54 do 0,68, což odpovídá interpretaci průměrná až dobrá shoda. Dle názoru autorů by ověření shody mezi hodnotiteli mělo být součástí řízení kvality v imunologické laboratoři alespoň při zácviku nového pracovníka nebo při přechodu na jiné diagnostiky. Autoři doporučují analyzovat shodu pomocí Cohenova kappa a nikoli pouhým procentuálním vyjádřením shody.
Detection of autoantibodies by indirect immunofluorescence microscopy is one of the principal method of the immunological laboratory diagnostic procedures. This method is essential for the diagnosis and monitoring of various autoimmune immunopathological diseases. The results of this tests are always dependent on the experience of the evaluator. It is common for evaluators to alternate or for a new worker to be trained. In those cases, the continuity of the results is at the risk. For this reason, it is appropriate to verify the agreement between evaluators. The aim of this study was to examine the agreement between three evaluators of immunofluorescence tests. Within 4 months, 163 samples were evaluated for the presence of antibodies against autoantigens of cytoplasmic granules of neutrophils ANCA, 301 samples for antibodies against endomysium, and 772 samples for antibodies against nuclear antigens ANA. Cohen’s kappa (κ) or weighted Cohen’s kappa (κwlin ) in combination with agreement expressed as a percentage were used to determine the inter-observer agreement. Overall, the agreement between the monitored evaluators was characterized as good. In the qualitative comparison (positive/negative), the κ value ranged from 0.79 to 1.00. In the quantitative evaluation, the lowest agreement, expressed by the value of κ wlin , was found for ANA 0.82 and the best for ANCA 0.98. The greatest differences were observed in differentiating of the fluorescence patterns of ANA and ANCA. In this case, values of kappa were in the range from 0.54 to 0.68, which was interpreted as moderate to substantial agreement. In the opinion of the authors, verification of agreement between evaluators should be a part of quality control in the immunology laboratory at least during the training of a new evaluater or when transitioning to other diagnostics. The authors recommend to analyze the agreement using Cohen’s kappa, rather than just a simple agreement expressed as a percentage.
INTRODUCTION: Reports on the immunogenicity and efficacy of the Spikevax® vaccine against SARS-CoV-2 in immunodeficient patients are still scarce. We aimed to evaluate the safety and immunogenicity of the vaccine in patients with primary humoral immunodeficiency. METHODS: We enrolled 46 patients, including 34 patients with common variable immunodeficiency (CVID), 10 patients with unclassified hypogammaglobulinemia (HypoIg), and 2 patients with X-linked agammaglobulinemia. We collected the blood samples before vaccination (D 0), and 10 days (D +38) and 90 days (D +118) after the second vaccination. Further, we quantified SARS-CoV-2-specific T-cell response (QuantiFERON ELISA test), serum anti-RBD IgG, and anti-RBD IgA-specific antibodies (enzyme immunoassay). RESULTS: We found that the vaccination elicited predominantly mild adverse events, comparable to healthy population. Vaccination response negatively correlated with a value of Immune Deficiency and Dysregulation Activity in all measured parameters. D +38, seroconversion for anti-RBD IgG and anti-RBD IgA was observed in 65% and 21% CVID patients, respectively. SARS-CoV-2-specific T-cell response was detected in less than 50% of CVID patients. Meanwhile, HypoIg patients had 100%, 90%, and 60% positivity rates for anti-RBD IgG, anti-RBD IgA, and T-cell response, respectively. Three months after the second vaccination, 82% of the responders remained positive for anti-RBD IgG, but only less than 50% remained positive for T-cell activity in CVIDs. Low immunogenicity was observed in patients with lung involvement and/or rituximab treatment history. No SARS-CoV-2 infection was reported within 6 months after the second vaccination. CONCLUSION: Spikevax® seems to be safe with satisfactory immunogenicity in patients with primary humoral immunodeficiency.
- MeSH
- Common Variable Immunodeficiency * therapy MeSH
- COVID-19 * prevention & control MeSH
- Immunoglobulin A MeSH
- Immunoglobulin G MeSH
- Humans MeSH
- RNA, Messenger MeSH
- SARS-CoV-2 MeSH
- Immunologic Deficiency Syndromes * MeSH
- Vaccination MeSH
- COVID-19 Vaccines * adverse effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Publication type
- Meeting Abstract MeSH
INTRODUCTION: To date, there is not generally accepted and universal indicator of activity, and functional integrity of the small intestine in patients with coeliac disease. The aim of our study was to investigate whether serum concentrations of the non-essential amino acids citrulline and ornithine might have this function. METHODS: We examined serum citrulline and ornithine concentrations in a subgroup of patients with proven coeliac disease and healthy controls (blood donors). RESULTS: A total of 94 patients with coeliac disease (29 men, mean age 53 ± 18 years; 65 women, mean age 44 ± 14 years) and 35 healthy controls (blood donors) in whom coeliac disease was serologically excluded (10 men, mean age 51 ± 14 years; 25 women, mean age 46 ± 12 years) were included in the study. Significantly lower concentrations of serum ornithine were found in patients with coeliac disease (mean 65 ± 3 μmol/L; median 63 μmol/L, IQR 34 μmol/L, p < 0.001). No statistically nor clinically significant differences were found in the citrulline concentrations between the study and control group. CONCLUSIONS: Serum ornithine (but not citrulline) may be useful for assessing the functional status of the small intestine in uncomplicated coeliac disease. Further studies involving more detailed analysis of dietary and metabolic changes in patients will be needed to reach definitive conclusions.
- MeSH
- Celiac Disease * MeSH
- Citrulline * metabolism MeSH
- Diet MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Ornithine metabolism MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Úvod a cíle: Laminarin je nízkomolekulární (504 Da) větvený glukózový polysacharid [ (1®3) -b-D-glukan], který je schopen modulovat humorální a buněčnou imunitní odpověď, a to nespecifickou i specifickou. Laminarin se vyznačuje anti-tumorózní aktivitou, neboť indukuje apoptózu a ovlivňuje intestinální mikrobiota. Cílem studie bylo vyšetřit anti-laminarinové protilátky u pacientů s kolorektálním karcinomem. Metody: Do prospektivní studie bylo zahrnuto 46 jedinců, z toho 14 kontrol (5 mužů, 9 žen, věk 29–80, průměr 55 ± 13) a 32 pacientů s kolorektálním karcinomem (14 mužů, 18 žen, věk 46–86, průměr 66 ± 11). Dva pacienti z CRC skupiny byli vyřazeni pro zjištěnou odlehlou hodnotu. Z 30 pacientů s CRC mělo 12 pravostranný kolorektální karcinom (12/30, 40 %). Většina pacientů s CRC měla stadium III (13/30, 43 %) nebo IV (13/30, 43 %). Pacienti měli převážně středně diferencovaný (15/30, 50 %) nebo nízce diferencovaný (11/30, 37 %) karcinom. Vzorky byly odebírány z periferní žilní krve a sérové IgG protilátky proti laminarinu byly stanoveny metodou ELISA v jednotkách U/ml. Výsledky: Sérové protilátky proti laminarinu byly signifikantně vyšší u kontrol ve srovnání s pacienty s CRC (16,23 ± 6,60; 11,41 ± 5,53; p = 0,015) a u kontrol ve srovnání s pacienty s levostranným CRC (11,38 ± 5,39; p = 0,046). Významný rozdíl byl pozorován mezi kontrolami a CRC III. stadiem (11,01 ± 3,36; p = 0,017); mezi kontrolami a CRC IV. stadiem (10,98 ± 6,06; p = 0,049). Anti-laminarinové protilátky byly signifikantně nižší u středně diferencovaného CRC ve srovnání s kontrolami (10,78 ± 5,22; p = 0,020), avšak nikoli u nízce diferencovaného CRC (12,10 ± 6,28; p = 0,755). Nebyl prokázán rozdíl mezi kontrolami a ženami s CRC (11,94 ± 6,39; p = 0,092). Byl potvrzen signifikantní rozdíl mezi kontrolami a muži s CRC (10,72 ± 4,32; p = 0,017). Závěr: Sérové protilátky proti laminarinu byly signifikantně nižší u pacientů s CRC a u podskupin osob s kolorektálním karcinomem.
Introduction and objectives: Laminarin is a low molecular weight (504 Da) glucose branched polysaccharide which modulates humoral and cellular immune response, both non-specific and specific. Laminarin possesses anti-tumorous activity as it induces apoptosis and modulates the colonic microbiota. The aim of our current study was to evaluate anti-laminarin antibodies in colorectal carcinoma. Methods: A total of 46 individuals were enrolled in the prospective study including 14 controls (5 men, 9 women, age 29–80, mean 55 ± 13) and 32 patients with colorectal carcinoma, CRC (14 men, 18 women, age 46–86, mean 66 ± 11). Two outliers were identified in the CRC group. Out of 30 CRC patients, 12 individuals had right-sided CRC (12/30; 40%). Majority of the CRC patients had stage III (13/30; 43%) or IV (13/30; 43%) cancer. Most of the CRC patients had moderately (15/30; 50%) or poorly (11/30; 37%) differentiated CRC. Samples were obtained from the peripheral venous blood and investigation of the serum IgG anti-laminarin antibodies was performed by means of ELISA and measured in U/mL. Results: Serum anti-laminarin antibodies were significantly higher in controls compared to the CRC group (16.23 ± 6.60; 11.41 ± 5.53; p = 0.015) and in controls compared to left-sided carcinoma (11.38 ± 5.39; p = 0.046). A statistically significant difference was observed between controls and CRC stage III (11.01 ± 3.36; p = 0.017) and between controls and CRC stage IV (10.98 ± 6.06; p = 0.049). Anti-laminarin antibodies were significantly lower in moderately differentiated CRC compared to controls (10.78 ± 5.22; p = 0.020), but not in poorly differentiated CRC (12.10 ± 6.28; p = 0.755). No difference was identified between controls and females with CRC (11.94 ± 6.39; p = 0.092). There was a significant difference between controls and males with CRC (10.72 ± 4.32; p = 0.017). Conclusion: Serum anti-laminarin antibodies were significantly lower in the CRC group and CRC subgroups compared to controls.
- Keywords
- anti-laminarinové protilátky,
- MeSH
- Cellulases analysis MeSH
- Colorectal Neoplasms * physiopathology MeSH
- Humans MeSH
- Biomarkers, Tumor MeSH
- Prospective Studies MeSH
- Check Tag
- Humans MeSH
Introduction: The amniotic fluid nicotinamide phosphoribosyltransferase (NAMPT) levels have not been compared among women with preterm prelabor rupture of membranes (PPROM) comorbid with intra-amniotic infection, sterile intra-amniotic inflammation (IAI), colonization, or without IAI and microbial invasion of the amniotic cavity (MIAC). Therefore, the main aim was to quantify the amniotic fluid NAMPT in women with PPROM complicated by intra-amniotic infection, sterile IAI, or colonization. The second aim was to characterize the diagnostic indices of NAMPT to reveal IAI. The third aim was to determine whether the cervical fluid and maternal serum NAMPT quantitation might be of value in the identification of intra-amniotic inflammatory complications in PPROM.Methods of study: NAMPT levels in amniotic fluid, cervical fluid, and maternal serum were assessed in three independent cohorts of women with singleton pregnancies complicated by PPROM between 24+0 and 36+6 weeks of gestation consisting of 88, 121, and 88 women, respectively. Amniotic fluid samples were obtained by transabdominal amniocentesis, cervical fluid samples were obtained using a Dacron polyester swab and maternal blood was obtained by venipuncture of the cubital vein. The NAMPT levels were measured by an enzyme-linked immunosorbent assay. Testing for MIAC and IAI was performed on all women, who were then categorized into four subgroups: intra-amniotic infection (MIAC and IAI), sterile IAI (IAI alone), colonization (MIAC alone), and without MIAC and IAI.Results: Women with intra-amniotic infection and women with sterile IAI had higher NAMPT levels than did women with colonization and women without MIAC and IAI (intra-amniotic infection: median 73.6 ng/mL, sterile IAI: median 55.5 ng/mL, colonization: median 12.1 ng/mL, without MIAC and IAI: 10.6 ng/mL; p < .0001). An amniotic fluid NAMPT level of 37 ng/mL was the best value for the detection of intra-amniotic infection in women with PPROM. Cervical fluid (p = .51) and maternal serum (p = .50) NAMPT levels did not reflect intra-amniotic inflammatory complications in women with PPROM.Conclusions: Intra-amniotic infection and sterile IAI are associated with higher NAMPT levels in amniotic fluid but not in cervical fluid or maternal serum in women with PPROM. Amniotic fluid NAMPT might be a marker for invasive identification of IAI in PPROM.
- MeSH
- Chorioamnionitis * diagnosis MeSH
- Gestational Age MeSH
- Humans MeSH
- Nicotinamide Phosphoribosyltransferase MeSH
- Infant, Newborn MeSH
- Amniotic Fluid MeSH
- Fetal Membranes, Premature Rupture * MeSH
- Pregnancy MeSH
- Inflammation MeSH
- Check Tag
- Humans MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
