Agata Burska - Academia.edu (original) (raw)

Papers by Agata Burska

Annales Umcs Pharmacia, 2008

Pharmacogenomics, Jul 1, 2014

Pharmacogenomics in rheumatoid arthritis: how close are we to the clinic? Frederique Ponchel

Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society, Jan 7, 2015

Immune age-related abnormalities may synergise with osteoarthritis (OA) pathology. We explored wh... more Immune age-related abnormalities may synergise with osteoarthritis (OA) pathology. We explored whether abnormalities in the blood immune cell composition are present in OA, beyond defects typically associated with ageing. Blood was collected from 121 healthy controls (HC) and 114 OA patients. Synovial biopsies were obtained from another 52 OA patients. Flow cytometry was used to establish the frequencies of lineage subsets, naïve, memory and regulatory T and B-cells, cells with an abnormal phenotype related to inflammation (IRC) and memory-like CD8(+) T-cells. Multivariate analysis of covariance (MANCOVA) was used to determine whether the relative subset frequencies differed between HC and OA, controlling for age. Expected histology and T/B-cell infiltration were observed. Following age adjusted analysis, we confirmed the lack of age association in HC for CD4(+), B, NK and NKT cells but a negative trend for CD8(+) T-cells. In OA, CD4(+) and B-cell frequency were lower compared to HC...

Annals of the Rheumatic Diseases, 2015

ABSTRACT

Annals of the Rheumatic Diseases, 2015

ABSTRACT Background Immuno-senescence and inflammageing are features of the ageing immune system.... more ABSTRACT Background Immuno-senescence and inflammageing are features of the ageing immune system. Such age-related abnormalities may be synergising with structural defects of the musculoskeletal system augmenting the development of OA. Our aim was to establish if abnormalities of blood immune cell composition were associated with OA, beyond defects already associated with ageing. Methods Blood was collected from 120 healthy controls (age 18–69) to establish variations associated with age and 110 OA patients (age 49–85). Synovial tissue biopsies were obtained for 52 OA patients. We examined loss or acquisition of age-related changes in blood immune cells composition using flow-cytometry to establish frequencies of CD4/CD8, B, NK-cells. T and B-cells were analysed further for phenotypes including an inflammation related cell (IRC) subset. Immunohistochemistry was used to analyse immune cell infiltration in OA synovial tissue. Results OA synovial tissue had a normal appearance in 13/52 samples. In 28/52 samples diffuse infiltration of T and B-cells could be observed while formation of small aggregates was found in 10 cases. The presence of an ectopic germinal centre-like structure was only seen in one sample. Lineage analysis showed no change in relation with age for NK, CD4, and B-cells, weak decline in CD8 ( rho = -0.300, p = 0.019) and increase in NKT ( rho = 0.315, p = 0.012). Phenotyping T/B-cells revealed clear age-related changes with reduction of naïve CD4+T-cell (rho = 0.817, p < 0.0001), increased Treg (rho = 0.501, p = 0.001), increased naive B-cells (rho = -0.501, p = 0.002) and reduced memory (rho = -0.518, p = 0.002). In OA, NK cells become positively related to age ( rho = 0.350, p < 0.0001), CD4 and B-cells negatively ( rho = -0.318, p = 0.001, rho = -0.260,p = 0.006 respectively). The CD8 relationship was lost. Naïve CD4 cells appeared to be particularly affected with increased frequencies in 32/110 patients. Treg were reduced in 41/105 patients irrespective of age. IRC were only increased in 16 patients. B-cell subsets were also affected resulting in loss of age-relationships observed in health. We observed that longer disease duration was associated with loss of CD4+T cells ( rho = -0.297, p = 0.025). IRC frequency was also associated with disease duration ( rho = 0.248, p = 0.058) and were also more frequent in patients affected in the hip (p = 0.002) or foot (p = 0.023). We observed no further association with B-cell subsets/phenotypes. Conclusion This analysis of the immune cell composition of the blood of OA patients suggests that immune dysfunction is present in OA beyond what is directly related to ageing. The relationship to severity of OA inflammation requires further investigation. The therapeutic implications of this warrant further study.

Annals of the Rheumatic Diseases, 2015

ABSTRACT Background Lack of accurate early diagnostic testing of Rheumatoid Arthritis (RA) remain... more ABSTRACT Background Lack of accurate early diagnostic testing of Rheumatoid Arthritis (RA) remains the limiting factor for early treatment to achieve remission. We hypothesised that molecular pathways implicated in RA pathology in the joint can inform a biomarker discovery programme based on flow-cytometry phenotyping of blood cells. Based on published work, we selected 74 subset/phenotypes and used high-dimensional dataset analysis to established their potential value in discriminating patients from an early arthritis clinic with <6 months symptoms who developed RA from those with other rheumatic diseases or non-persistent inflammation. Methods 46 patients were enrolled. 6–8 colour flowcytometry was performed using standard protocols. We recorded% of positive cells when 2 populations could be distinguished, and levels of expression (MFI) for single populations. A random forest ordered predictors from these 74 subset/phenotypes according to importance. Then a classification tree was fitted based on the most important factors and finally the variables identified from the classification tree were fitted in a logistic regression. Results 23 of the 46 patients had RA, 11 non-persistent inflammation and 12 other rheumatic diseases (AS, SPA, gout, OA and reactive). 47 individual phenotypes were analysed and 36 additional ones using a combination of 2 markers. No difference in lineage representation was found; significant difference were observed for 11/47 subsets (P < 0.025) with 3 more borderline significant (P < 0.075). These suggested particularly high significant differences on CD4 and NKT cells as well as lesser one on B, NK and monocytes. Due to the low number of patients, multivariable analysis was limited. We ran un-supervised cluster analysis which separated 2 groups (RA/non-RA) quite efficiently with 5-RA and 6-non-RA misclassified. A 3-node classification tree using 47 phenotypes classified 20/23 RA patients correctly. The 3 phenotypes showing best discrimination power were IL-6R+NKT-cells, naïve CD4+T-cells and CCR6+ monocytes. A logistic regression confirmed that these 3 phenotypes were highly significant phenotypes (P < 0.005). A random forest combining all phenotypes suggested that 8 CD4+T-cells phenotypes, 1 CD8+ T-cells, 2 B-cells, 1 monocyte and 1 NKT-cells have potential value for discriminating RA from non-RA patients based on accuracy. Conclusion Despite the small sample size, this analysis demonstrated the value of hypothesis driven marker analysis, with 12 of the 47 phenotypes predicted to have potential showing significant differences. By triangulating different analysis approaches, the robustness of the findings was improved giving confidence in the identification of relevant biomarkers.

Pharmacogenomics, 2014

Pharmacogenomics in rheumatoid arthritis: how close are we to the clinic? Frederique Ponchel

Annales UMCS, Pharmacia, 2008

Arthritis Research & Therapy, 2014

Introduction: Interleukin-7 (IL-7) is a cytokine essential for T-cell lymphopoiesis, survival and... more Introduction: Interleukin-7 (IL-7) is a cytokine essential for T-cell lymphopoiesis, survival and polarization with an emerging role in autoimmunity. We previously demonstrated reduced levels of circulating IL-7 in rheumatoid arthritis (RA), although high amounts are expressed in joints, suggesting differences between systemic and synovial effects. We observed healthy levels of IL-7 in 48% of RA patients in clinical remission (CR) and aimed to investigate the consequences of IL-7 deficiency on T-cell responses.

Annales UMCS, Pharmacia, 2008

Endocrine Abstracts, 2013

Annals of the Rheumatic Diseases, 2012

Annales Umcs Pharmacia, 2008

Pharmacogenomics, Jul 1, 2014

Pharmacogenomics in rheumatoid arthritis: how close are we to the clinic? Frederique Ponchel

Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society, Jan 7, 2015

Immune age-related abnormalities may synergise with osteoarthritis (OA) pathology. We explored wh... more Immune age-related abnormalities may synergise with osteoarthritis (OA) pathology. We explored whether abnormalities in the blood immune cell composition are present in OA, beyond defects typically associated with ageing. Blood was collected from 121 healthy controls (HC) and 114 OA patients. Synovial biopsies were obtained from another 52 OA patients. Flow cytometry was used to establish the frequencies of lineage subsets, naïve, memory and regulatory T and B-cells, cells with an abnormal phenotype related to inflammation (IRC) and memory-like CD8(+) T-cells. Multivariate analysis of covariance (MANCOVA) was used to determine whether the relative subset frequencies differed between HC and OA, controlling for age. Expected histology and T/B-cell infiltration were observed. Following age adjusted analysis, we confirmed the lack of age association in HC for CD4(+), B, NK and NKT cells but a negative trend for CD8(+) T-cells. In OA, CD4(+) and B-cell frequency were lower compared to HC...

Annals of the Rheumatic Diseases, 2015

ABSTRACT

Annals of the Rheumatic Diseases, 2015

ABSTRACT Background Immuno-senescence and inflammageing are features of the ageing immune system.... more ABSTRACT Background Immuno-senescence and inflammageing are features of the ageing immune system. Such age-related abnormalities may be synergising with structural defects of the musculoskeletal system augmenting the development of OA. Our aim was to establish if abnormalities of blood immune cell composition were associated with OA, beyond defects already associated with ageing. Methods Blood was collected from 120 healthy controls (age 18–69) to establish variations associated with age and 110 OA patients (age 49–85). Synovial tissue biopsies were obtained for 52 OA patients. We examined loss or acquisition of age-related changes in blood immune cells composition using flow-cytometry to establish frequencies of CD4/CD8, B, NK-cells. T and B-cells were analysed further for phenotypes including an inflammation related cell (IRC) subset. Immunohistochemistry was used to analyse immune cell infiltration in OA synovial tissue. Results OA synovial tissue had a normal appearance in 13/52 samples. In 28/52 samples diffuse infiltration of T and B-cells could be observed while formation of small aggregates was found in 10 cases. The presence of an ectopic germinal centre-like structure was only seen in one sample. Lineage analysis showed no change in relation with age for NK, CD4, and B-cells, weak decline in CD8 ( rho = -0.300, p = 0.019) and increase in NKT ( rho = 0.315, p = 0.012). Phenotyping T/B-cells revealed clear age-related changes with reduction of naïve CD4+T-cell (rho = 0.817, p < 0.0001), increased Treg (rho = 0.501, p = 0.001), increased naive B-cells (rho = -0.501, p = 0.002) and reduced memory (rho = -0.518, p = 0.002). In OA, NK cells become positively related to age ( rho = 0.350, p < 0.0001), CD4 and B-cells negatively ( rho = -0.318, p = 0.001, rho = -0.260,p = 0.006 respectively). The CD8 relationship was lost. Naïve CD4 cells appeared to be particularly affected with increased frequencies in 32/110 patients. Treg were reduced in 41/105 patients irrespective of age. IRC were only increased in 16 patients. B-cell subsets were also affected resulting in loss of age-relationships observed in health. We observed that longer disease duration was associated with loss of CD4+T cells ( rho = -0.297, p = 0.025). IRC frequency was also associated with disease duration ( rho = 0.248, p = 0.058) and were also more frequent in patients affected in the hip (p = 0.002) or foot (p = 0.023). We observed no further association with B-cell subsets/phenotypes. Conclusion This analysis of the immune cell composition of the blood of OA patients suggests that immune dysfunction is present in OA beyond what is directly related to ageing. The relationship to severity of OA inflammation requires further investigation. The therapeutic implications of this warrant further study.

Annals of the Rheumatic Diseases, 2015

ABSTRACT Background Lack of accurate early diagnostic testing of Rheumatoid Arthritis (RA) remain... more ABSTRACT Background Lack of accurate early diagnostic testing of Rheumatoid Arthritis (RA) remains the limiting factor for early treatment to achieve remission. We hypothesised that molecular pathways implicated in RA pathology in the joint can inform a biomarker discovery programme based on flow-cytometry phenotyping of blood cells. Based on published work, we selected 74 subset/phenotypes and used high-dimensional dataset analysis to established their potential value in discriminating patients from an early arthritis clinic with <6 months symptoms who developed RA from those with other rheumatic diseases or non-persistent inflammation. Methods 46 patients were enrolled. 6–8 colour flowcytometry was performed using standard protocols. We recorded% of positive cells when 2 populations could be distinguished, and levels of expression (MFI) for single populations. A random forest ordered predictors from these 74 subset/phenotypes according to importance. Then a classification tree was fitted based on the most important factors and finally the variables identified from the classification tree were fitted in a logistic regression. Results 23 of the 46 patients had RA, 11 non-persistent inflammation and 12 other rheumatic diseases (AS, SPA, gout, OA and reactive). 47 individual phenotypes were analysed and 36 additional ones using a combination of 2 markers. No difference in lineage representation was found; significant difference were observed for 11/47 subsets (P < 0.025) with 3 more borderline significant (P < 0.075). These suggested particularly high significant differences on CD4 and NKT cells as well as lesser one on B, NK and monocytes. Due to the low number of patients, multivariable analysis was limited. We ran un-supervised cluster analysis which separated 2 groups (RA/non-RA) quite efficiently with 5-RA and 6-non-RA misclassified. A 3-node classification tree using 47 phenotypes classified 20/23 RA patients correctly. The 3 phenotypes showing best discrimination power were IL-6R+NKT-cells, naïve CD4+T-cells and CCR6+ monocytes. A logistic regression confirmed that these 3 phenotypes were highly significant phenotypes (P < 0.005). A random forest combining all phenotypes suggested that 8 CD4+T-cells phenotypes, 1 CD8+ T-cells, 2 B-cells, 1 monocyte and 1 NKT-cells have potential value for discriminating RA from non-RA patients based on accuracy. Conclusion Despite the small sample size, this analysis demonstrated the value of hypothesis driven marker analysis, with 12 of the 47 phenotypes predicted to have potential showing significant differences. By triangulating different analysis approaches, the robustness of the findings was improved giving confidence in the identification of relevant biomarkers.

Pharmacogenomics, 2014

Pharmacogenomics in rheumatoid arthritis: how close are we to the clinic? Frederique Ponchel

Annales UMCS, Pharmacia, 2008

Arthritis Research & Therapy, 2014

Introduction: Interleukin-7 (IL-7) is a cytokine essential for T-cell lymphopoiesis, survival and... more Introduction: Interleukin-7 (IL-7) is a cytokine essential for T-cell lymphopoiesis, survival and polarization with an emerging role in autoimmunity. We previously demonstrated reduced levels of circulating IL-7 in rheumatoid arthritis (RA), although high amounts are expressed in joints, suggesting differences between systemic and synovial effects. We observed healthy levels of IL-7 in 48% of RA patients in clinical remission (CR) and aimed to investigate the consequences of IL-7 deficiency on T-cell responses.

Annales UMCS, Pharmacia, 2008

Endocrine Abstracts, 2013

Annals of the Rheumatic Diseases, 2012