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1.
J Clin Endocrinol Metab ; 108(11): e1214-e1223, 2023 10 18.
Article in English | MEDLINE | ID: mdl-37247379

ABSTRACT

CONTEXT: There is no early, first-trimester risk estimation available to predict later (gestational week 24-28) gestational diabetes mellitus (GDM); however, it would be beneficial to start an early treatment to prevent the development of complications. OBJECTIVE: We aimed to identify early, first-trimester prediction markers for GDM. METHODS: The present case-control study is based on the study cohort of a Hungarian biobank containing biological samples and follow-up data from 2545 pregnant women. Oxidative-nitrative stress-related parameters, steroid hormone, and metabolite levels were measured in the serum/plasma samples collected at the end of the first trimester from 55 randomly selected control and 55 women who developed GDM later. RESULTS: Pregnant women who developed GDM later during the pregnancy were older and had higher body mass index. The following parameters showed higher concentration in their serum/plasma samples: fructosamine, total antioxidant capacity, testosterone, cortisone, 21-deoxycortisol; soluble urokinase plasminogen activator receptor, dehydroepiandrosterone sulfate, dihydrotestosterone, cortisol, and 11-deoxycorticosterone levels were lower. Analyzing these variables using a forward stepwise multivariate logistic regression model, we established a GDM prediction model with a specificity of 96.6% and sensitivity of 97.5% (included variables: fructosamine, cortisol, cortisone, 11-deoxycorticosterone, SuPAR). CONCLUSION: Based on these measurements, we accurately predict the development of later-onset GDM (24th-28th weeks of pregnancy). Early risk estimation provides the opportunity for targeted prevention and the timely treatment of GDM. Prevention and slowing the progression of GDM result in a lower lifelong metabolic risk for both mother and offspring.


Subject(s)
Cortisone , Diabetes, Gestational , Female , Humans , Pregnancy , Desoxycorticosterone , Diabetes, Gestational/diagnosis , Fructosamine , Hydrocortisone , Pregnancy Trimester, First , Case-Control Studies
2.
Lab Med ; 53(2): 206-209, 2022 Mar 07.
Article in English | MEDLINE | ID: mdl-34415328

ABSTRACT

Platelets have a role in vascular complications of COVID-19-related viral coagulopathy. Although immune-induced thrombocytopenia has been described mostly in moderate-to-severe COVID-19, the prognostic role of platelet count in COVID-19 is still controversial. Pseudothrombocytopenia has been reported to represent COVID-19-associated coagulopathy in critical illness, and transient EDTA-dependent pseudothrombocytopenia lasting less than 3 weeks was described in a patient with severe acute COVID-19 pneumonia. In our case study, EDTA-induced pseudothrombocytopenia was still present at 9 months after an initial SARS-CoV-2 virus infection in an apparently recovered 60 year old man. The persistence of antinucleocapside and antispike antibodies 9 months after the initial infection suggests that EDTA-induced pseudothrombocytopenia may be related to anti-SARS-CoV-2 IgG or IgM antibodies. We should acknowledge the possibility that pseudothrombocytopenia may also appear in some patients after seroconversion after the launch of large-scale vaccination programs.


Subject(s)
COVID-19 , Thrombocytopenia , COVID-19/complications , Edetic Acid , Humans , Immunoglobulin G , Immunoglobulin M , Male , Middle Aged , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Thrombocytopenia/chemically induced
3.
Biomarkers ; 26(5): 443-449, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33825610

ABSTRACT

There is a lack of non-invasive biomarkers to identify lupus nephritis (LN). Soluble urokinase plasminogen activator receptor (suPAR) is a sensitive biomarker of ongoing inflammation and a potential marker of podocyte dysfunction. The aim of this study was to assess urine and plasma suPAR in LN. 14 systemic lupus erythematosus (SLE) patients with newly diagnosed LN, 8 active SLE patients (SLEDAI >8) without LN and 31 healthy individuals were enrolled. Urine and plasma samples were taken before the initiation of LN induction therapy, and monthly thereafter. Global and renal disease activity were defined using the SLEDAI-2K and the SLEDAI-2K renal domain score, respectively. suPAR concentrations were measured with the suPARnostic Flex ELISA assay. Urine and plasma suPAR levels were elevated in SLE patients with active LN compared with resolved LN and healthy controls. Urine suPAR levels were comparable to healthy controls in active SLE without LN. Urine and plasma suPAR levels were higher before than after the initiation of LN induction therapy. Prospective follow-up measurements also suggested that urine suPAR levels raised again in patients with a relapse of LN according to SLEDAI-2K renal domain score, whereas plasma suPAR levels did not correlate with renal disease activity. Urine suPAR is a promising LN activity biomarker, given its isolated elevation in urine in active LN and pronounced decrease with LN improvement.


Subject(s)
Lupus Nephritis/diagnosis , Receptors, Urokinase Plasminogen Activator/metabolism , Adolescent , Adult , Aged , Biomarkers/blood , Biomarkers/urine , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunosuppressive Agents/therapeutic use , Longitudinal Studies , Lupus Nephritis/blood , Lupus Nephritis/drug therapy , Lupus Nephritis/urine , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Receptors, Urokinase Plasminogen Activator/blood , Time Factors , Treatment Outcome , Urinalysis , Young Adult
4.
EJIFCC ; 31(3): 225-230, 2020 Sep.
Article in English | MEDLINE | ID: mdl-33061877

ABSTRACT

BACKGROUND: Vitamin D deficiency has been linked to a higher risk of prostate cancer. We tested the hypothesis that vitamin D levels would have an impact on prostate specific antigen (PSA) levels. METHODS: From our laboratory database we selected 5136 male patients with simultaneously determined vitamin D and PSA levels. Subgroups of several age cohorts with different vitamin D levels were created and PSA 95 percentile values were assessed. The independent effect of vitamin D levels and age on PSA levels was determined with logistic regression. RESULTS: PSA levels increased with age, while no difference was identified in PSA levels in different vitamin D subgroups. CONCLUSION: Vitamin D levels do not have an effect on PSA. Hence, there is no need to adjust PSA reference ranges and threshold values to vitamin D levels during the process of decision making.

5.
Clin Gastroenterol Hepatol ; 17(12): 2506-2513.e2, 2019 11.
Article in English | MEDLINE | ID: mdl-30630103

ABSTRACT

BACKGROUND & AIMS: There is evidence that it is safe and effective for patients with inflammatory bowel diseases (IBD) to switch from maintenance therapy with an original infliximab drug to a biosimilar, but little is known about outcomes of reverse switches and/or multiple switches. We aimed to evaluate the effects of a reverse switch (from a biosimilar to Remicade) in a real-life cohort. METHODS: We performed a prospective observational study of 174 unselected and consecutive patients with IBD (136 with Crohn's disease [CD] and 38 with ulcerative colitis [UC]) who received maintenance therapy with the biosimilar in Hungary. In September 2017, patients were switched from the biosimilar (CT-P13) to Remicade, due to reimbursement policies. In our cohort, 8% (n = 14) patients had been previously exposed to the originator Remicade. We collected clinical and biochemical information from patients at baseline (time of the switch) and 16 and 24 weeks thereafter. Clinical remission was defined as a Crohn's disease activity index <150 points or no fistula drainage, or a partial Mayo score <3 points for patients with UC. Serum drug trough levels and anti-drug antibodies were measured at baseline and week 16. RESULTS: There was no significant difference in the proportion of patients in clinical remission at week 8 before the switch (82.5% with CD and 82.9% with UC), at baseline (80.6% with CD and 81.6% with UC), at week 16 (77.5% with CD and 83.7% with UC), or at week 24 (CD 76.3% with CD and 84.9% with UC) (P = .60 among groups for patients with CD and P = .98 among groups for patients with UC). For all patients, mean serum trough levels of infliximab were 5.33 ± 4.70 µg/mL at baseline and 5.69 ± 4.94 µg/mL at week 16 (P = .71); we did not find significant differences in prevalence of anti-drug antibody at baseline (16.2%) compared with week 16 (16.9%) (P = .87). Four infusion reactions occurred, until week 24 of follow up. There was no difference in outcomes or trough or antidrug antibody levels between patients with or without previous exposure to Remicade. CONCLUSIONS: We collected data from a real-life cohort of patients with CD or UC who were switched from maintenance therapy with a biosimilar to Remicade or were treated with only Remicade. No significant changes were observed in remission, trough levels, or antidrug antibodies in patients switched from the biosimilar to Remicade. No new safety signals were detected.


Subject(s)
Biosimilar Pharmaceuticals/therapeutic use , Gastrointestinal Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , Adult , Antibodies/blood , Female , Gastrointestinal Agents/blood , Gastrointestinal Agents/immunology , Humans , Infliximab/blood , Infliximab/immunology , Male , Prospective Studies , Remission Induction , Young Adult
6.
Pathobiology ; 85(3): 201-210, 2018.
Article in English | MEDLINE | ID: mdl-29212085

ABSTRACT

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic, progressive immune-mediated inflammatory disease, driven primarily by Th1 and Th17 cells. Anti-TNF therapies are successfully used in AS to achieve and maintain remission. However, their influence on the composition of T-cell subsets is not clear. We aimed to characterize the changes in the T-cell repertoire after a long-term anti-TNF treatment in AS patients. METHODS: Twenty-two AS patients under long-term anti-TNF therapy were evaluated (15 anti-TNF responders and 7 nonresponders). A wide range of cell subtypes was analyzed with flow cytometry and compared with therapy-naïve and short-term data too. RESULTS: Key findings include decreased proportions of naïve CD4 and CD8 cells, increased frequencies of Th1 and Th17 cells and higher Th1/Th2 ratios in the long-term anti-TNF-treated patients (responders, nonresponders and total), which was found to be significant not only when compared with healthy controls, but also with therapy-naïve and short-term anti-TNF-treated AS patients. We noted several alterations within the various activated T-cell subsets - increase in CD4HLADR cells in responders, in CD8HLADR cells in the whole AS group and in responders, and in CD4CD25 cells in responders, and decrease in CD4CD69 cell percentages in long-term treated patients - becoming evident only after long-term anti-TNF therapy. CONCLUSIONS: This study provides a comprehensive assessment of the impact of anti-TNF therapy on the T-cell repertoire in AS. Changes in T-cell phenotype seem to develop progressively during therapy, even in inactive disease, and reflect an ongoing effector T-cell differentiation and activation, along with the parallel compensatory increase in regulatory T cells.


Subject(s)
Antirheumatic Agents/therapeutic use , Spondylitis, Ankylosing/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , CD4-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/drug effects , Female , Flow Cytometry , Follow-Up Studies , Humans , Male , Middle Aged , Phenotype , Spondylitis, Ankylosing/immunology , T-Lymphocyte Subsets/drug effects , T-Lymphocytes, Regulatory/drug effects , Th1 Cells/drug effects , Th17 Cells/drug effects , Th2 Cells/drug effects , Tumor Necrosis Factor-alpha/immunology
7.
Mediators Inflamm ; 2017: 6894374, 2017.
Article in English | MEDLINE | ID: mdl-29209104

ABSTRACT

Data on the impact of biological therapies on the T-cell phenotype in rheumatoid arthritis are limited. Here, we prospectively measured the percentages of 15 circulating T-cell subtypes using flow cytometry. We obtained transversal and longitudinal data in 30 anti-TNF responders, 19 secondary anti-TNF nonresponders, and 43 IL-6R antagonist responders, before, 8 weeks and at least 6 months after biological therapy. Untreated RA patients and healthy controls were also included. The important findings are the following: (1) the proportion of regulatory T-cells (Tregs) which are decreased in untreated RA patients becomes normal in all long-term-treated groups; (2) in anti-TNF responders as well as in nonresponders, the frequencies of naïve CD4+ and CD8+ cells are lower, whereas those of proinflammatory Th1, Th2, and Th17 cells and HLA-DR+-activated cells are higher than those in untreated RA or healthy controls; (3) in IL-6R responders, Th1 proportion is decreased, while that of Th2 and Th17 is increased as compared to that in anti-TNF-treated patients and controls; (4) pending confirmation, a CD4CD69 ratio < 2.43 at baseline, could be useful to predict a good therapeutic response to anti-TNF therapy. This study provides comprehensive information regarding the long-term impacts of those biological therapies on the ecotaxis of T-cells in RA. The ClinicalTrials.gov registration number of our study is NCT03266822.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Receptors, Interleukin-6/metabolism , T-Lymphocyte Subsets/metabolism , Tumor Necrosis Factor-alpha/metabolism , Adalimumab/therapeutic use , Adult , Aged , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Arthritis, Rheumatoid/immunology , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , Certolizumab Pegol/therapeutic use , Cross-Sectional Studies , Etanercept/therapeutic use , Female , Flow Cytometry , Humans , Infliximab/therapeutic use , Male , Middle Aged , Receptors, Interleukin-6/antagonists & inhibitors , T-Lymphocytes, Regulatory/metabolism , Th17 Cells/metabolism , Th2 Cells/metabolism , Tumor Necrosis Factor-alpha/antagonists & inhibitors
8.
Inflamm Bowel Dis ; 23(11): 1908-1915, 2017 11.
Article in English | MEDLINE | ID: mdl-28922253

ABSTRACT

BACKGROUND: It has been previously shown that biosimilar infliximab CT-P13 is effective and safe in inducing remission in inflammatory bowel diseases. We report here the 1-year outcomes from a prospective nationwide inflammatory bowel disease cohort. METHODS: A prospective, nationwide, multicenter, observational cohort was designed to examine the efficacy and safety of CT-P13 in the induction and maintenance treatment of Crohn's disease (CD) and ulcerative colitis (UC). Demographic data were collected and a harmonized monitoring strategy was applied. Clinical remission, response, and biochemical response were evaluated at weeks 14, 30, and 54, respectively. Safety data were registered. RESULTS: Three hundred fifty-three consecutive inflammatory bowel disease (209 CD and 144 UC) patients were included, of which 229 patients reached the week 54 endpoint at final evaluation. Age at disease onset: 24/28 years (median, interquartile range: 19-34/22-39) in patients with CD/UC. Forty-nine, 53, 48% and 86, 81 and 65% of patients with CD reached clinical remission and response by weeks 14, 30, and 54, respectively. Clinical remission and response rates were 56, 41, 43% and 74, 66, 50% in patients with UC. Clinical efficacy was influenced by previous anti-tumor necrosis factor (TNF) exposure in patients with a drug holiday beyond 1 year. The mean C-reactive protein level decreased significantly in both CD and UC by week 14 and was maintained throughout the 1-year follow-up (both UC/CD: P < 0.001). Thirty-one (8.8%) patients had infusion reactions and 32 (9%) patients had infections. Antidrug antibody positivity rates were significantly higher throughout patients with previous anti-TNF exposure; concomitant azathioprine prevented antidrug antibody formation in anti-TNF-naive patients with CD. CONCLUSIONS: Results from this prospective nationwide cohort confirm that CT-P13 is effective and safe in inducing and maintaining long-term remission in both CD and UC. Efficacy was influenced by previous anti-TNF exposure; no new safety signals were detected.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Gastrointestinal Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , Antibodies, Monoclonal/adverse effects , Biosimilar Pharmaceuticals/therapeutic use , C-Reactive Protein/analysis , Drug Monitoring , Female , Gastrointestinal Agents/adverse effects , Humans , Hungary/epidemiology , Inflammatory Bowel Diseases/immunology , Infliximab , Male , Prospective Studies , Remission Induction , Treatment Outcome , Young Adult
9.
BMC Gastroenterol ; 17(1): 97, 2017 Aug 08.
Article in English | MEDLINE | ID: mdl-28789636

ABSTRACT

BACKGROUND: Therapeutic drug monitoring (TDM) aid therapeutic decision making in patients with inflammatory bowel disease (IBD) who lose response to anti-TNF therapy. Our aim was to evaluate the frequency and predictive factors of loss of response (LOR) to adalimumab using TDM in IBD patients. METHODS: One hundred twelve IBD patients (with 214 TDM measurements, CD/UC 84/28, male/female 50/62, mean age CD/UC: 36/35 years) were enrolled in this consecutive cohort from two referral centres in Hungary. Demographic data were comprehensively collected and harmonized monitoring strategy was applied. Previous and current therapy, laboratory data and clinical activity were recorded at the time of TDM. Patients were evaluated either at the time of suspected LOR or during follow-up. TDM measurements were determined by commercial ELISA (LISA TRACKER, Theradiag, France). RESULTS: Among 112 IBD patients, LOR/drug persistence was 25.9%/74.1%. The cumulative ADA positivity (>10 ng/mL) and low TL (<5.0 µg/mL) was 12.1% and 17.8% after 1 year and 17.3% and 29.5% after 2 years of adalimumab therapy. Dose intensification was needed in 29.5% of the patients. Female gender and ADA positivity were associated with LOR (female gender: p < 0.001, OR:7.8 CI 95%: 2.5-24.3, ADA positivity: p = 0.007 OR:3.6 CI 95%: 1.4-9.5). CONCLUSIONS: ADA development, low TL and need for dose intensification were frequent during adalimumab therapy and support the selective use of TDM in IBD patients treated with adalimumab. ADA positivity and gender were predictors of LOR.


Subject(s)
Adalimumab/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Drug Monitoring/methods , Adult , Cohort Studies , Dose-Response Relationship, Drug , Drug Tolerance , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Humans , Hungary , Male , Treatment Outcome
11.
J Asthma ; 53(9): 900-6, 2016 11.
Article in English | MEDLINE | ID: mdl-27340880

ABSTRACT

OBJECTIVE: Asthma often complicates pregnancy and represents a risk for complications. Periostin is considered as a biomarker of asthma; however, as it also plays a role in normal gestation, pregnancy may influence circulating periostin levels. This is the first study assessing periostin in asthmatic pregnancy. METHODS: Plasma periostin levels were investigated in asthma (asthmatic non-pregnant, ANP; N = 19) and asthmatic pregnancy (AP; N = 14), compared to healthy non-pregnant controls (HNP; N = 12) and healthy pregnant women (HP; N = 17). The relationship between periostin levels and asthma control determinants was also evaluated. The diagnostic efficacy of periostin to detect uncontrolled asthma was analyzed using ROC analysis. RESULTS: Plasma periostin levels were similar in the HNP and ANP (55.68 [37.21-67.20] vs. 45.25 [32.67-64.55], p > 0.05), and elevated in the HP (68.81 [57.34-98.84] ng/mL, p = 0.02 vs. HNP) and AP groups (54.02 [44.30-74.94] ng/mL, p = 0.0346 vs. ANP). Periostin levels of the two pregnant groups were similar (p > 0.05). In AP women periostin correlated negatively with FEV1 (r = -0.5516) and positively with Raw (r = 0.5535; both p < 0.05). CONCLUSIONS: Pregnancy itself increases circulating periostin levels and this elevation is detectable in asthmatic pregnancy as well. Although periostin correlates with lung function in asthmatic pregnancy, periostin as a biomarker has to be handled with caution in pregnant patients due to the influence of pregnancy on its plasma level.


Subject(s)
Asthma/blood , Cell Adhesion Molecules/blood , Pregnancy Complications/blood , Pregnancy/blood , Adult , Asthma/physiopathology , Biomarkers/blood , Case-Control Studies , Female , Humans , Pregnancy Complications/physiopathology , Pulmonary Ventilation , ROC Curve , Reference Values
12.
J Crohns Colitis ; 10(2): 133-40, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26661272

ABSTRACT

BACKGROUND AND AIMS: Biosimilar infliximab CT-P13 is approved for all indications of the originator product in Europe. Prospective data on its efficacy, safety, and immunogenicity in inflammatory bowel diseases are lacking. METHODS: A prospective, nationwide, multicentre, observational cohort was designed to examine the efficacy, safety, and immunogenicity of CT-P13 infliximab biosimilar in the induction treatment of Crohn's disease [CD] and ulcerative colitis [UC]. Demographic data were collected and a harmonised monitoring strategy was applied. Early clinical remission, response, and early biochemical response were evaluated at Week 14, steroid-free clinical remission was evaluated at Week 30. Therapeutic drug level was monitored using a conventional enzyme-linked immunosorbent assay. RESULTS: In all, 210 consecutive inflammatory bowel disease [126 CD and 84 UC] patients were included in the present cohort. At Week 14, 81.4% of CD and 77.6% of UC patients showed clinical response and 53.6% of CD and 58.6% of UC patients were in clinical remission. Clinical remission rates at Week 14 were significantly higher in CD and UC patients who were infliximab naïve, compared with those with previous exposure to the originator compound [p < 0.05]. Until Week 30, adverse events were experienced in 17.1% of all patients. Infusion reactions and infectious adverse events occurred in 6.6% and 5.7% of all patients, respectively. CONCLUSIONS: This prospective multicentre cohort shows that CT-P13 is safe and effective in the induction of clinical remission and response in both CD and UC. Patients with previous infliximab exposure exhibited decreased response rates and were more likely to develop allergic reactions.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Biosimilar Pharmaceuticals/administration & dosage , Inflammatory Bowel Diseases/drug therapy , Infliximab/administration & dosage , Adult , Female , Follow-Up Studies , Gastrointestinal Agents/administration & dosage , Humans , Male , Prospective Studies , Remission Induction , Time Factors , Treatment Outcome , Young Adult
13.
Article in English | MEDLINE | ID: mdl-26451099

ABSTRACT

INTRODUCTION: The association between vitamin D and clinical parameters in obstructive lung diseases (OLDs), including COPD and bronchial asthma, was previously investigated. As asthma-COPD overlap syndrome (ACOS) is a new clinical entity, the prevalence of vitamin D levels in ACOS is unknown. AIM: Our aim was to assess the levels of circulating vitamin D (25-hydroxyvitamin D [25(OH)D]) in different OLDs, including ACOS patients, and its correlation with clinical parameters. METHODS: A total of 106 men and women (control, n=21; asthma, n=44; COPD, n=21; and ACOS, n=20) were involved in the study. All patients underwent detailed clinical examinations; disease control and severity was assessed by disease-specific questionnaires (COPD assessment test, asthma control test, and modified Medical Research Council); furthermore, 25(OH)D levels were measured in all patients. RESULTS: The 25(OH)D level was significantly lower in ACOS and COPD groups compared to asthma group (16.86±1.79 ng/mL and 14.27±1.88 ng/mL vs 25.66±1.91 ng/mL). A positive correlation was found between 25(OH)D level and forced expiratory volume in 1 second (r=0.4433; P<0.0001), forced vital capacity (FVC) (r=0.3741; P=0.0004), forced expiratory flow between 25% and 75% of FVC (r=0.4179; P<0.0001), and peak expiratory flow (r=0.4846; P<0.0001) in OLD patient groups. Asthma control test total scores and the 25(OH)D level showed a positive correlation in the ACOS (r=0.4761; P=0.0339) but not in the asthma group. Higher COPD assessment test total scores correlated with decreased 25(OH)D in ACOS (r=-0.4446; P=0.0495); however, this was not observed in the COPD group. CONCLUSION: Vitamin D deficiency is present in ACOS patients and circulating 25(OH)D level may affect disease control and severity.


Subject(s)
Asthma/physiopathology , Forced Expiratory Volume/physiology , Pulmonary Disease, Chronic Obstructive/physiopathology , Vitamin D Deficiency/epidemiology , Vitamin D/analogs & derivatives , Adult , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , Quality of Life , Risk Factors , Surveys and Questionnaires , Vitamin D/blood
14.
Clin Chem Lab Med ; 53(11): 1799-805, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25894644

ABSTRACT

BACKGROUND: Urokinase plasminogen activator receptor (uPAR) is a key component of the fibrinolytic system involved in extracellular matrix remodeling and angiogenesis. Novel animal models supported the key role of uPAR not only in fibrosis but also in systemic sclerosis (SSc)-related microvascular abnormalities. The aim of this study was to investigate plasma soluble uPAR (suPAR) levels in SSc, and their association with organ-specific involvement. METHODS: suPAR concentrations were measured by ELISA in SSc patient (n=83) and in healthy controls (n=29). Simultaneously, CRP and ESR were assessed. Detailed clinical data including skin, lung, heart and microvascular characteristics were evaluated at sampling. RESULTS: suPAR values were higher in SSc patients than in controls. Subgroup analysis showed higher suPAR values in diffuse cutaneous- than in limited cutaneous SSc and correlated with anti-Scl-70+. suPAR levels also associated with pulmonary function test parameters of fibrosis, presence of microvascular lesions (e.g., Raynaud phenomenon, naifold capillaroscopic abnormalities and digital ulcers) and arthritis. CONCLUSIONS: Our data indicate that suPAR might be a valuable early diagnostic marker of SSc which also correlates with disease severity.


Subject(s)
Microvessels/abnormalities , Receptors, Urokinase Plasminogen Activator/blood , Scleroderma, Systemic/blood , Scleroderma, Systemic/pathology , Adult , Aged , Enzyme-Linked Immunosorbent Assay , Female , Fibrosis , Humans , Male , Middle Aged , Receptors, Urokinase Plasminogen Activator/deficiency , Receptors, Urokinase Plasminogen Activator/genetics , Scleroderma, Systemic/complications , Solubility
15.
PLoS One ; 9(8): e104298, 2014.
Article in English | MEDLINE | ID: mdl-25098248

ABSTRACT

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a systemic dysfunction of T-cells. In this study we tested the impact of DMARD and anti-TNF agents on short-term activation characteristics of T-cells. We enrolled 12 patients with newly diagnosed RA (naïve RA) who were treated with methothrexate (MTX) and glucocorticsteroid (GCS) and 22 patients with established RA non responding to conventional DMARD therapy who were treated with different anti-TNF agents. Nine healthy volunteers served as controls. Blood samples were taken at baseline, then at 4th and 8th week of therapy. The characteristics of several intracellular activation processes during short-term activation of T-cells including cytoplasmic Ca(2+) level, mitochondrial Ca(2+) level, reactive oxygen species (ROS) and nitric oxide (NO) generation were determined by a novel flow-cytometry technique. At baseline, the tested processes were comparable to controls in naïve RA. During GCS therapy, cytoplasmic Ca(2+) level and ROS generation decreased. After the addition of MTX to GCS cytoplasmic Ca(2+) level became comparable to controls, while ROS generation decreased further. In DMARD non responders, cytoplasmic Ca(2+) level was higher than controls at baseline. The cytoplasmic Ca(2+) level became comparable to controls and ROS generation decreased during each of the three anti-TNF-α agent therapies. Mitochondrial Ca(2+) level and NO generation were unaltered in all of the patient groups. These results indicate that intracellular machinery is affected in T-cells of RA patients. This may alter the behavior of T-cells during activation. Different therapeutic approaches may modulate the abnormal T-cell functions.


Subject(s)
Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/drug therapy , Lymphocyte Activation/drug effects , T-Lymphocytes/immunology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/pathology , Calcium/immunology , Female , Follow-Up Studies , Glucocorticoids/administration & dosage , Humans , Immunosuppressive Agents/administration & dosage , Male , Methotrexate/administration & dosage , Middle Aged , Nitric Oxide/immunology , Reactive Oxygen Species/immunology , T-Lymphocytes/pathology , Tumor Necrosis Factor-alpha/immunology
16.
Clin Rheumatol ; 33(2): 175-85, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23934385

ABSTRACT

Rheumatoid arthritis (RA) is an autoimmune disease characterized by abnormal prevalence of Th1, Th2, Th17, and regulatory (Treg) subsets. Some data suggest that these subsets are influenced by anti-RA agents. Follow-up studies monitoring T cell phenotype in response to therapy are limited. We investigated the alteration of CD4+ T cell subset distribution after the initiation of disease-modifying antirheumatic drug (DMARD) (with glucocorticosteroid (GCS) and methotrexate (MTX)) and anti-TNFα therapy. We enrolled 19 treatment naive (early) RA patients and initiated GCS (in a dose of 16 mg/day for 4 weeks; then 8 mg/day). MTX, 10 mg/week, was started at week 4. We also enrolled 32 RA patients unresponsive to DMARD and initiated anti-TNFα therapy: adalimumab (ADA), 40 mg/2 weeks, n = 12; etanercept (ETA), 50 mg/weeks, n = 12; or infliximab (IFX) on week 0, 2, and 6, 3 mg/kg bw, n = 8. Blood was taken before and 4 and 8 weeks after the initiation of therapy. Ten volunteers served as controls. The T cell phenotype was assessed with flow cytometry. In early RA, Th1, Th2, and Th17 prevalence was higher, while Treg prevalence was lower than normal. GCS alone decreased Th2 prevalence. GCS + MTX decreased Th17 prevalence. Immune phenotype in unresponsive RA before anti-TNF therapy was as in early RA. Four and 8 weeks after initiating anti-TNF therapy, Th1 prevalence was higher than baseline in ETA or IFX, while it was stable in ADA groups. Th2 prevalence was higher than normal in ADA or IFX, while normalized in ETA group. In each group, Treg prevalence increased, while Th17 prevalence was at the baseline. The proinflammatory immune phenotype is normalized only under GCS + MTX combination in early RA. Anti-TNFα therapy exhibit marked effects on all the cell populations investigated (except Th17); some slight differences in this action exist between ADA, ETA, and IFX therapy.


Subject(s)
Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/drug therapy , Biological Products/therapeutic use , CD4-Positive T-Lymphocytes/drug effects , Lymphocyte Subsets/drug effects , Adalimumab , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Arthritis, Rheumatoid/blood , Etanercept , Female , Follow-Up Studies , Glucocorticoids/administration & dosage , Humans , Immunoglobulin G/administration & dosage , Infliximab , Male , Methotrexate/administration & dosage , Middle Aged , Phenotype , Prevalence , Receptors, Tumor Necrosis Factor/administration & dosage , Th17 Cells/drug effects
17.
Joint Bone Spine ; 80(1): 96-8, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22999906

ABSTRACT

Recent studies demonstrated that soluble urokinase plasminogen activator receptor (suPAR) is a valuable marker in the recognition of an inflammatory response. Ongoing inflammation leads to elevated plasma suPAR levels. We aimed to characterize plasma suPAR levels in ankylosing spondylitis (AS) patients compared to healthy individuals in order to reveal if suPAR could be used as a clinical marker of inflammation in AS. We measured plasma suPAR and C-reactive protein (CRP) levels as well as erythrocyte sedimentation rate (ESR) in 33 AS patients at various stages of disease duration and activity and 29 healthy controls. CRP and ESR values were higher in AS patients than in healthy individuals, while suPAR values were comparable (median [interquartile range]: 2.97 [2.57-3.80] ng/mL vs. 2.80 [2.06-3.42] ng/mL, P>0.05). In AS patients, a correlation was detected between BASDAI scores and CRP as well as ESR values but not suPAR levels (P=0.0005, r=0.57 and P=0.01, r=0.43, respectively). Unlike in many other inflammatory conditions, plasma suPAR levels do not reflect inflammation in AS. To assess the inflammatory status in AS, ESR and particularly CRP values are still more appropriate clinical markers. In line with earlier findings, our results indicate that, unlike suPAR, both of these markers are positively correlated with disease activity in AS.


Subject(s)
Receptors, Urokinase Plasminogen Activator/blood , Spondylitis, Ankylosing/blood , Adult , Aged , Biomarkers/blood , Blood Sedimentation , C-Reactive Protein/analysis , Female , Humans , Male , Middle Aged
18.
Neurol Sci ; 34(7): 1151-5, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23070628

ABSTRACT

Aseptic inflammation due to activated immune cells has been implicated in the pathomechanism of migraine. We measured the prevalence of regulatory T cells (Tregs), along with that of CD4(+)/CD8(+) lymphocytes and their Th1/Th2 commitment in pediatric migraine. Children and adolescents suffering from migraine without aura, migraine with aura and hemiplegic migraine ictally (n = 53, 27, and 20, respectively), also interictally (n = 33) were recruited and compared to 24 healthy children. Our results indicated comparable prevalence of Tregs, CD4(+) and Th1/Th2 committed cells. CD8(+) prevalence was lower, and CD4(+)/CD8(+) ratio was higher in ictal phase irrespective of the subtype of migraine. No association between CD8(+) prevalence and gender, body weight, disease onset and attack duration in migraine subtypes was found. CD8(+) prevalence was normal in patients in interictal phase. These results suggest the absence of major systemic alteration of adaptive immunity in children and adolescents suffering from migraine; however, a transient decrease of CD8(+) prevalence during the ictal phase was detected irrespective of the subtype of migraine.


Subject(s)
Lymphocyte Subsets/metabolism , Migraine Disorders/blood , Migraine Disorders/diagnosis , Adolescent , Age Factors , Child , Child, Preschool , Female , Humans , Lymphocyte Subsets/immunology , Lymphocyte Subsets/pathology , Male , Migraine Disorders/immunology , Migraine Disorders/pathology
19.
Biomarkers ; 17(8): 758-63, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23033975

ABSTRACT

OBJECTIVE: Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of systemic inflammation. We aimed to characterize plasma suPAR levels in SLE patients. METHODS: We measured plasma suPAR, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in 89 SLE patients and 29 healthy controls. RESULTS: suPAR and ESR values were higher in SLE than in controls, while CRP levels were comparable. ROC analysis of suPAR levels indicated a cut-off value of 5.70 ng/mL to distinguish patients with high disease activity (SLEDAI >8). CONCLUSION: suPAR might be an objective marker for identifying SLE patients with active disease.


Subject(s)
Biomarkers/blood , Lupus Erythematosus, Systemic/blood , Receptors, Urokinase Plasminogen Activator/blood , Adult , Aged , Blood Sedimentation , C-Reactive Protein/metabolism , Female , Humans , Lupus Erythematosus, Systemic/diagnosis , Male , Middle Aged , Prognosis , ROC Curve , Solubility
20.
Clin Dev Immunol ; 2012: 808724, 2012.
Article in English | MEDLINE | ID: mdl-21969839

ABSTRACT

Our aim was to assess the phenotype of T-cell subsets in patients with ankylosing spondylitis (AS), a chronic inflammatory rheumatic disease. In addition, we also tested short-term T-cell activation characteristics. Measurements were done in 13 AS patients before and during the intravenous therapy with anti-TNF agent infliximab (IFX). Flow cytometry was used to determine T-cell subsets in peripheral blood and their intracellular signaling during activation. The prevalence of Th2 and Th17 cells responsible for the regulation of adaptive immunity was higher in AS than in 9 healthy controls. Although IFX therapy improved patients' condition, immune phenotype did not normalize. Cytoplasmic and mitochondrial calcium responses of CD4+ and CD8+ cells to a specific activation were delayed, while NO generation was increased in AS. NO generation normalized sooner upon IFX than calcium response. These results suggest an abnormal immune phenotype with functional disturbances of CD4+ and CD8+ cells in AS.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Spondylitis, Ankylosing/immunology , Spondylitis, Ankylosing/therapy , T-Lymphocyte Subsets/immunology , Adaptive Immunity , Adult , Antibodies, Monoclonal/administration & dosage , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Female , Flow Cytometry , Humans , Infliximab , Lymphocyte Activation , Male , Middle Aged , Phenotype , T-Lymphocytes/immunology , Treatment Outcome
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