Calcium Influx Kinetics and the Characteristics of Potassium Channels in Peripheral T Lymphocytes in Systemic Sclerosis

Pathobiology ◽  
2020 ◽  
Vol 87 (5) ◽  
pp. 311-316
Author(s):  
Gergely Toldi ◽  
Nóra Legány ◽  
Imre Ocsovszki ◽  
Attila Balog
Keyword(s):  
Systemic Sclerosis ◽  
T Lymphocytes ◽  
Potassium Channels ◽  
Calcium Influx ◽  
Th1 Cells ◽  
Healthy Controls ◽  
Cytoplasmic Calcium ◽  
Cd8 Cells ◽  
Channel Inhibition ◽  
Influx Kinetics

<b><i>Background:</i></b> Systemic sclerosis (SSc) is a chronic, immune-mediated, connective tissue disease causing microvascular abnormalities and fibrosis. The cytoplasmic calcium influx kinetics in T lymphocytes governs lymphocyte activation in this inflammatory process. The inhibition of Kv1.3 and IKCa1 potassium channels reduces calcium influx. <b><i>Methods:</i></b> This study aimed to analyze cytoplasmic calcium influx kinetics following activation in Th1, Th2, and CD8 cells in peripheral blood of 12 healthy individuals and 16 patients with systemic sclerosis using flow cytometry. We also evaluated the effect of the specific inhibition of the Kv1.3 and IKCa1 potassium channels. <b><i>Results:</i></b> We observed higher levels of activation in CD8 compared with Th1 cells in SSc. However, the activation of CD8 cells was lower in SSc compared to healthy controls. Moreover, activation of Th1 lymphocytes was slower in SSc than in healthy controls. The inhibition of IKCa1 channels decreased the activation of Th1 cells, while the inhibition of Kv1.3 channels modified the dynamics of activation of Th1 and Th2 lymphocytes in SSc. <b><i>Conclusion:</i></b> Th1 and CD8 cells demonstrate specific activation dynamics and sensitivity to potassium channel inhibition in SSc, distinguishing this condition both from healthy controls and other autoimmune diseases.

scholarly journals The effects of Kv1.3 and IKCa1 potassium channel inhibition on calcium influx of human peripheral T lymphocytes in rheumatoid arthritis

Immunobiology ◽  
2013 ◽  
Vol 218 (3) ◽  
pp. 311-316 ◽  
Author(s):  
Gergely Toldi ◽  
Anna Bajnok ◽  
Diána Dobi ◽  
Ambrus Kaposi ◽  
László Kovács ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Lymphocytes ◽  
Potassium Channel ◽  
Calcium Influx ◽  
Channel Inhibition

Changes of Subsets of DC 1 in the Bone Marrow of Severe Aplastic Anemia Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3712-3712
Author(s):  
Guangsheng He ◽  
Zhonghong Shao ◽  
De Pei Wu ◽  
Xiao Ma ◽  
Aining Sun
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
T Lymphocytes ◽  
Aplastic Anemia ◽  
Severe Aplastic Anemia ◽  
Stable Form ◽  
Th1 Cells ◽  
Th1 Cell ◽  
Cd8 Cells ◽  
Normal Controls

Abstract Objective To measure the changes of subsets of dendritic cells 1 (DC1) in the bone marrow of severe aplastic anemia (SAA) patients and evaluate the relationships between the CD11c+CD83+cells and Th1 cells, CD3+CD8+ cells or hematopoietic function. Methods By FACS, the quantity and ratio of CD11c+CD1a+ cells, CD11c+CD83+ cells, Th1 cells, and CD3+CD8+ cells in the bone marrow of SAA patients and normal controls were detected respectively. The relationships between CD3+CD8+ cells and Ret or ANC, between Th1 cells and CD3+CD8+ cells, Ret or ANC, between CD11c+CD83+ cells, and Th1 cells, CD3+CD8+ cells, Ret or ANC were evaluated. Results In normal control’s bone marrow, the percentages of Th1 cells, CD11c+CD1a+ cells, CD11c+CD83+ cells and ratio of CD11c+CD83+ /CD11c+CD1a+ was 0.42±0.30%, 0.38±0.29%, 0.37±0.32% and 1.07±0.10 respectively. In the untreated SAA patient’s bone marrow, they were 4.87±0.54%, 1.73±0.24%, 3.38±0.56% and 2.21±0.32 respectively, and increased markedly(p<0.01). In recovering SAA patient’s bone marrow, the percentages of Th1 cells, CD11c+CD1a+ cells and CD11c+CD83+ cells decreased significantly[0.53±0.22%, 0.61±0.23%, 0.65±0.22%, respectively (p<0.01)]. The ratio of CD11c+CD83+/CD11c+ CD1a+ of recovering SAA patients was 1.37±0.25 which was similar to that of normal controls (p>0.05). The percentages of CD3+CD8+ cells of untreated SAA patients was 32.32±10.22%, and that of recovering SAA patients decreased to 13.67%±5.24 significantly (p<0.01). The percentages of CD3+CD8+ cells of SAA patients were correlated to their Ret and ANC (P<0.05) negatively. Their Th1 cell percentages were correlated to their CD3+CD8+ cells positively (P<0.01), but to their Ret and ANC negatively(p<0.01). SAA patient’s CD11c+CD83+ cell percentages were correlated to their Th1 cell and CD3+CD8+ cells positively (P<0.01, P<0.05), but to their Ret and ANC negatively(p<0.01). Conclusion Both immature DC1 and activated DC1 increased in the bone marrow of SAA patients, and the balance of subsets of DC1 shifted from stable form to active one, which might promote Th0 cells to polarize to Th1 cells, then cause the over-function of T lymphocytes and hematopoietic failure in SAA.

scholarly journals AB0691 ANALYSIS OF SARS-COV-2 ANTIBODIES IN NON-COVID-19 PATIENTS: COMPARISON BETWEEN SYSTEMIC SCLEROSIS PATIENTS AND HEALTHY CONTROLS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1379.1-1379
Author(s):  
L. Giardullo ◽  
C. Rotondo ◽  
A. Corrado ◽  
N. Maruotti ◽  
R. Colia ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Systemic Sclerosis ◽  
Autoimmune Disease ◽  
Reverse Transcriptase ◽  
Real Time ◽  
Polymerase Chain Reaction Assay ◽  
Nuclear Antigen ◽  
Healthy Controls ◽  
Chain Reaction ◽  
Polymerase Chain

Background:Previous study evidenced a cross-reactivity between Sars-Cov-2 antibodies and autoimmune tissue antigen involved in connective tissue diseases, as nuclear antigen (NA), extractable nuclear antigen (ENA), histone and collagen (1). No study has been published about the titer of Sars-Cov-2 antibodies in non-infected patients with autoimmune disease.Objectives:To evaluate the titer of SARS-CoV-2 antibodies in non-COVID-19 patients and compare it between systemic sclerosis (SSc) patients and healthy controls (HC).Methods:A total of 58 patients with SSc (who fulfilled ACR/EULAR 2013 SSc classification criteria) and 18 HC were enrolled. Sera of all participants were collected, and SARS-CoV-2 antibodies (IgG and IgM) were evaluated by means ELISA. In all participants swabs for SARS-CoV-2 by real-time reverse-transcriptase-polymerase-chain-reaction assay were reported negative. Demographic, clinical, and autoimmune serological characteristics of SSc patients were recorded. The normal distribution was assessed using the Shapiro–Wilk’s test. Exclusion criteria was previous or actual Sars-Cov-2 infection. Comparisons between study groups of patients were evaluated by the Student’s t-test or Mann – Whitney U-test as appropriate. The differences between categorial variables were assessed by Pearson chi-square or Fisher’s exact test, as opportune. Statistical significance was set at p ≤ 0.05.Results:We observed significant differences between SSc patients and HC in serum levels of Sars-Cov-2 antibodies (IgG: 1,4±2,1 AU/ml vs 0,36±0,19 AU/ml respectively (p=0,001); and IgM: 2,5±3,1 AU/ml vs 0,8±0,7 AU/ml (p=0,022)). In 5 SSc patients was found titer of Sars-Cov-2 antibodies (IgG) exceeding the cut-off, but the control of swabs for SARS-CoV-2 by real-time reverse-transcriptase-polymerase-chain-reaction assay were negative. No significative differences in Sars-Cov-2 autoantibodies titer were found in subgroup of SSc patients with or without ILD or PAH, limited or diffuse skin subset, and different autoantibodies profile. Furthermore, antibodies titer was not associated with different drugs (steroid, methotrexate, mofetil-mycophenolate and bosentan) in use.Conclusion:A cross mimicking between Sars-Cov-2 antibodies and antinuclear antibodies or anti ENA could be hypothesized. Further studies are necessary to unravel the reliability of Sars-Cov-2 antibodies detection in autoimmune disease.References:[1]Vojdani, A., Vojdani, E., & Kharrazian, D. (2021). Reaction of human monoclonal antibodies to SARS-CoV-2 proteins with tissue antigens: Implications for autoimmune diseases. Frontiers in Immunology, 11, 3679Disclosure of Interests:None declared

scholarly journals FRI0226 OPTICAL COHERENCE TOMOGRAPHY OF THE SKIN DETECTS SCLERODERMA CHANGES IN CLINICALLY UNAFFECTED SKIN: AN OPPORTUNITY FOR EARLY DETECTION OF SYSTEMIC SCLEROSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 696.2-696
Author(s):  
G. Abignano ◽  
D. Temiz Karadağ ◽  
O. Gundogdu ◽  
G. Lettieri ◽  
M. C. Padula ◽  
...  
Keyword(s):  
At Risk ◽  
Clinical Trials ◽  
Optical Coherence Tomography ◽  
Systemic Sclerosis ◽  
Early Detection ◽  
Classification Criteria ◽  
Healthy Controls ◽  
Optical Coherence ◽  
Risk Patients ◽  
Unaffected Skin

Background:The Very Early Diagnosis Of Systemic Sclerosis (VEDOSS) study has shown that 82% of patients with Raynaud’s Phenomenon, specific ANA positivity and scleroderma pattern at nail fold videocapillaroscopy will fulfil classification criteria within 5 years. This is suggesting that there is a subclinical window of opportunity to diagnose systemic sclerosis (SSc) before clinical manifestations occur. In this scenario, a non-invasive tool to diagnose SSc in clinically unaffected skin might improve the early detection of disease in at risk-patients. Optical coherence tomography (OCT) of the skin has been shown to be a sensitive and accurate biomarker of skin fibrosis in SSc.Objectives:Here we aimed to assess the ability of skin OCT to “detect” SSc in clinically unaffected skin from a multicentre cohort.Methods:Dorsal forearm skin of SSc patients and matched-healthy controls (HC) was evaluated using VivoSight scanner (Michelson Diagnostics). Mean A-scans (mean OCT signal plotted against depth-in-tissue) were derived as previously described. Minimum Optical Density (MinOD), Maximum OD (MaxOD) and OD at 300 micron-depth (OD300) were calculated. Clinical involvement was assessed by an operator blinded to OCT findings using the mRSS. Receiver-operating characteristic (ROC) curve analysis was carried out for MinOD, MaxOD, and OD300 to evaluate their ability to discriminate between SSc and HC. Statistical analysis was performed using GraphPad Prism software V.7.0.Results:One hundred seventy four OCT images were collected from 87 subjects [43 SSc (39 Female, mean age 49.7±9.1 years) and 44 gender/age-matched healthy controls (HC) (36 Female, mean age 50.2±8.3 years)] in two different SSc centres. All patients fulfilled classification criteria for SSc. OCT measures demonstrated discriminative ability in SSc skin detection with any clinical skin involvement (0-3 at site of analysis) with an AUC of 0.73 (MinOD, 95%CI 0.64-0.81), 0.77 (MaxOD, 95%CI 0.7-0.85) and 0.82 (OD300, 95%CI 0.76-0.89); p<0.0001 for all as previously indicated. Most importantly, all three measures showed comparable performance in detecting scleroderma also in clinically unaffected skin (mRss=0 at site of analysis), with an AUC of 0.7 (95%CI 0.6-0.81, p=0.001), 0.72 (95%CI 0.61-0.83, p=0.0003) and 0.72 (95%CI 0.61-0.83, p=0.0003) for MinOD, MaxOD and OD300 respectively.Conclusion:Virtual biopsy by OCT recognises clinically unaffected skin of SSc patients from the HC skin. This is consistent with gene array data showing that scleroderma specific signatures are consistent in affected and clinically unaffected skin. These results inform future studies on at risk patients with clinically unaffected skin which may define a role for OCT in detecting subclinical SSc.Disclosure of Interests:Giuseppina Abignano: None declared, Duygu Temiz Karadağ: None declared, Ozcan Gundogdu: None declared, Giovanni Lettieri: None declared, Maria Carmela Padula: None declared, Angela Padula: None declared, Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), Salvatore D’Angelo: None declared, Francesco Del Galdo: None declared

scholarly journals AB0562 SLEEP HYGIENE: COULD IT BE A CONFOUNDING FACTOR FOR SLEEP QUALITY IN SYSTEMIC SCLEROSIS?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1578.2-1578
Author(s):  
N. Gokcen ◽  
A. Komac ◽  
F. Tuncer ◽  
A. Yazici ◽  
A. Cefle
Keyword(s):  
Systemic Sclerosis ◽  
Sleep Quality ◽  
Disease Activity ◽  
Beck Depression Inventory ◽  
Sleep Disturbances ◽  
Activity Index ◽  
Univariate Analysis ◽  
Sleep Hygiene ◽  
Healthy Controls ◽  
Clinical Variables

Background:Sleep disturbances have been described in Systemic Sclerosis (SSc). Confounding factors related to sleep quality are also investigated. Although sleep hygiene plays an important role in sleep quality, as far as we know, there are not enough data to show the effect of sleep hygiene on sleep quality of SSc.Objectives:To investigate sleep hygiene, its impact on sleep quality, and its association with demographic-clinical factors in patients with SSc, rheumatoid arthritis (RA), and healthy controls.Methods:The study was designed as cross-sectional. Forty-nine patients with SSc who fulfilled the 2013 ACR/EULAR classification criteria for SSc, 66 patients with RA who fulfilled 1987 revised classification criteria, and 30 healthy controls were included in the study. All participants were female. Demographic and clinical variables were documented. Disease activity index of both SSc and RA was calculated. SSc patients were assessed by questionnaires including Short Form 36 (SF-36), The Health Assessment Questionnaire Disability Index (HAQ-DI), Beck Anxiety and Beck Depression Inventory, Pittsburg Sleep Quality Index (PSQI), Sleep Hygiene Index (SHI). Additionally, RA patients and healthy controls were estimated by HAQ-DI, Beck Anxiety and Beck Depression Inventory, PSQI, and SHI. Logistic regression analysis was used to determine the predictors of sleep quality.Results:Preliminary results of the study were given. The baseline demographics were similar among groups. When comparing groups according to HAQ-DI, Beck Anxiety and Beck Depression Inventory, PSQI, and SHI, we found higher scores in SSc and RA rather than healthy controls (p<0.001, p=0.001, p=0.001, p<0.001, p=0.003; respectively). While depression and sleep hygiene were determined as the risk factors of sleep quality in SSc in univariate analysis, depression (OR=1.380, 95%CI: 1.065−1.784, p=0.015) and sleep hygiene (OR=1.201, 95%CI: 1.003−1.439, p=0.046) were also found in multivariate logistic model. In RA patients, while health status, depression, and anxiety were found as risk factors according to the univariate analysis, depression (OR=1.120, 95%CI: 1.006−1.245, p=0.038) was the only factor according to multivariate logistic model (Table).Conclusion:Although depression is a well-known clinical variable impacting on sleep quality, sleep hygiene should also be kept in mind as a confounding factor.References:[1]Milette K, Hudson M, Körner A, et al. Sleep disturbances in systemic sclerosis: evidence for the role of gastrointestinal symptoms, pain and pruritus. Rheumatology (Oxford). 2013 Sep;52(9):1715-20.[2]Sariyildiz MA, Batmaz I, Budulgan M, et al. Sleep quality in patients with systemic sclerosis: relationship between the clinical variables, depressive symptoms, functional status, and the quality of life. Rheumatol Int. 2013 Aug;33(8):1973-9.TableUnivariate logistic regression analysis of clinical variables to assess predictors of sleep qualitySystemic sclerosisRheumatoid arthritisOR (95% CI)pOR (95% CI)pHAQ-DI1.019 (0.882−1.177)0.8011.089 (1.011−1.173)0.025BDI score1.293 (1.082−1.547)0.0051.129 (1.036−1.230)0.006BAI score1.080 (0.997−1.169)0.0591.122 (1.038−1.214)0.004SHI1.200 (1.060−1.357)0.0041.048 (0.965−1.137)0.264Disease activitya0.707 (0.439−1.138)0.1531.446 (0.839−2.492)0.185aDisease activity was calculated by Valentini disease activity index for SSc and DAS28-CRP for RA.Disclosure of Interests:None declared

scholarly journals AB0450 PERIPHERAL MACROVASCULAR INVOLVEMENT IN SYSTEMIC SCLEROSIS AS COMPARED WITH HEALTHY CONTROLS: A SMALL COHORT STUDY BY COLOR AND SPECTRAL DOPPLER ULTRASONOGRAPHY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1252.2-1252
Author(s):  
R. D’alessandro ◽  
E. Garcia Gonzales ◽  
P. Falsetti ◽  
C. Baldi ◽  
F. Bellisai ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Clinical Features ◽  
Doppler Ultrasonography ◽  
Power Doppler ◽  
Ulnar Artery ◽  
Artery Occlusion ◽  
Power Doppler Ultrasonography ◽  
Digital Ulcers ◽  
Healthy Controls ◽  
History Of

Background:Together with autoimmune-inflammation and fibrosis, microvasculopathy is a hallmark of SSc. However, also macrovascular changes may occur including peripheral proliferative vasculopathy. Whether this changes may represent a specific SSc marker with a predictive value remains a matter of debate.[1,2,3]Objectives:To study peripheral macrovascular involvement by color doppler ultrasound (CDUS) with spectral wave analysis (SWA) in a cohort of 40 SSc patients as compared to healthy controls. To further analyze any differences among the SSc population.Methods:Forty SSc patients and 36 healthy controls were examined by CDUS with SWA of both hands. Macrovascular involvement was assessed by measuring the resistivity index (RI) of distal ulnar and radial arteries. Examinations were performed with an Esaote MyLab Twice machine equipped with a linear 10-22 MHz probe. Ultrasound examination was carried out by two independent rheumatologists blinded to clinical conditions of the patients. Statistical analysis was performed by using MaxStat software.Results:The RI index resulted increased in the SSc cohort as compared with healthy controls (left ulnar RI 0.977 vs 0.715; right ulnar RI 0.996 vs 0.699; left radial RI 0.988 vs 0.706; right radial RI 0.999 vs 0.688; p<0.001). SSc patients with an increased RI in one artery were more probable to have an increased RI in the other vessels too (r 2 = 0.35; p<0.01). In addition, 8 out of 40 SSc patients presented left ulnar artery occlusion (UAO) and 7 out of 40 SSc patients presented right UAO, of which 6 presented bilateral UAO. Awaiting to enlarge the cohort for further analysis, descriptive data regarding increased RI at CDUS/SWA and clinical features, including years from onset of the disease, subtype of SSc, mRSS, history of digital ulcers, interstitial lung disease and PAH are described in Table 1.Conclusion:Peripheral macrovascular involvement was observed in SSc patients as compared with healthy controls. Further studies will determine whether this feature may have specificity for diagnosis/prognosis in SSc.References:[1]Lescoat A, Yelnik CM, Coiffier G et al. Ulnar Artery Occlusion and Severity Markers of Vasculopathy in Systemic Sclerosis: A Multicenter Cross-Sectional Study. Arthritis Rheumatol. 2019;71:983-990.[2]Lescoat A, Coiffier G, Rouil A et al. Vascular Evaluation of the Hand by Power Doppler Ultrasonography and New Predictive Markers of Ischemic Digital Ulcers in Systemic Sclerosis: Results of a Prospective Pilot Study. Arthritis Care Res (Hoboken). 2017;69:543-551.[3]Schioppo T, Orenti A, Boracchi P, De Lucia O, Murgo A, Ingegnoli F. Evidence of macro- and micro-angiopathy in scleroderma: An integrated approach combining 22-MHz power Doppler ultrasonography and video-capillaroscopy. Microvasc Res. 2019;122:125-130.Table 1.Main clinical features of the SSc cohort (n=40) studied by CDUS for macrovascular involvement.SSc cohort (n = 40)Years from onsetrange (35 y – 0 y)mean = 10.5 yAutoantibodiesACA 13/40Anti-TopoI 14/40Other 13/40mRSSrange (0 -30)mean = 3ILD17/40PAH7/40Capillaroscopy patternEarly 10/40Active 11/40Late 6/40History of digital ulcers16/40Left ulnar IR0.977Left radial IR0.988Right ulnar IR0.996Right radial IR0.999Disclosure of Interests:None declared.

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