scholarly journals Differences in Maturation Status and Immune Phenotypes of Circulating Helios+ and Helios− Tregs and Their Disrupted Correlations With Monocyte Subsets in Autoantibody-Positive T1D Individuals

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuyue Zhang ◽  
Jie Zhang ◽  
Yun Shi ◽  
Min Shen ◽  
Hui Lv ◽  
...  
Keyword(s):  
Disease Duration ◽  
Effector Memory ◽  
Healthy Controls ◽  
Monocyte Subsets ◽  
Distinct Subset ◽  
Immune Phenotypes ◽  
Immunological Changes ◽  
Positive Correlations ◽  
Intermediate Monocytes

CD4 Tregs are involved in the regulation of various autoimmune diseases but believed to be highly heterogeneous. Studies have indicated that Helios controls a distinct subset of functional Tregs. However, the immunological changes in circulating Helios+ and Helios− Tregs are not fully explored in type 1 diabetes (T1D). Here, we elucidated the differences in maturation status and immune regulatory phenotypes of Helios+ and Helios− Tregs and their correlations with monocyte subsets in T1D individuals. As CD25−/low FOXP3+ Tregs also represent a subset of functional Tregs, we defined Tregs as FOXP3+CD127−/low and examined circulating Helios+ and Helios− Treg subpopulations in 68 autoantibody-positive T1D individuals and 68 age-matched healthy controls. We found that expression of both FOXP3 and CTLA4 diminished in Helios− Tregs, while the proportion of CD25−/low Tregs increased in Helios+ Tregs of T1D individuals. Although the frequencies of neither Helios+ nor Helios− Tregs were affected by investigated T1D genetic risk loci, Helios+ Tregs correlated with age at T1D diagnosis negatively and disease duration positively. Moreover, the negative correlation between central and effector memory proportions of Helios+ Tregs in healthy controls was disrupted in T1D individuals. Finally, regulatory non-classical and intermediate monocytes also decreased in T1D individuals, and positive correlations between these regulatory monocytes and Helios+/Helios− Treg subsets in healthy controls disappeared in T1D individuals. In conclusion, we demonstrated the alternations in maturation status and immune phenotypes in Helios+ and Helios− Treg subsets and revealed the missing association between these Treg subsets and monocyte subsets in T1D individuals, which might point out another option for elucidating T1D mechanisms.

scholarly journals Clinical autonomic dysfunction in narcolepsy type 1

SLEEP ◽  
2019 ◽  
Vol 42 (12) ◽  
Author(s):  
Lucie Barateau ◽  
Sofiene Chenini ◽  
Elisa Evangelista ◽  
Isabelle Jaussent ◽  
Regis Lopez ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Autonomic Dysfunction ◽  
Disease Duration ◽  
Poor Quality ◽  
Healthy Controls ◽  
Clinical Autonomic ◽  
And Gender ◽  
Drug Free

Abstract Study Objectives (1) To compare the presence of autonomic symptoms using the validated SCOPA-AUT questionnaire in untreated patients with narcolepsy type 1 (NT1) to healthy controls, (2) to study the determinants of a high total SCOPA-AUT score in NT1, and (3) to evaluate the effect of drug intake on SCOPA-AUT results in NT1. Methods The SCOPA-AUT questionnaire that evaluates gastrointestinal, urinary, cardiovascular, thermoregulatory, pupillomotor, and sexual dysfunction was completed by 92 consecutive drug-free adult NT1 patients (59 men, 39.1 ± 15.6 years old) and 109 healthy controls (63 men, 42.6 ± 18.2 years old). A subgroup of 59 NT1 patients completed the questionnaire a second time, under medication (delay between two evaluations: 1.28 ± 1.14 years). Results Compared to controls, NT1 patients were more frequently obese, had more dyslipidemia, with no difference for age and gender. The SCOPA-AUT score of NT1 was higher than in controls in crude and adjusted models. Patients experienced more problems than controls in all subdomains. A higher score in NT1 was associated with older age, longer disease duration, altered quality of life and more depressive symptoms, but not with orexin levels and disease severity. Among patients evaluated twice, the SCOPA-AUT score total did not differ according to treatment status, neither did each subdomain. Conclusion We captured a frequent and large spectrum of clinical autonomic dysfunction in NT1, with impairment in all SCOPA-AUT domains, without key impact of medication intake. This assessment may allow physicians to screen and treat various symptoms, often not spontaneously reported but associated with poor quality of life.

scholarly journals Distinct immune regulatory receptor profiles linked to altered monocyte subsets in sarcoidosis

2020 ◽  
pp. 00804-2020
Author(s):  
Simon D. Fraser ◽  
Michael G. Crooks ◽  
Paul M. Kaye ◽  
Simon P. Hart
Keyword(s):  
Inflammatory Responses ◽  
Pulmonary Sarcoidosis ◽  
Receptor Expression ◽  
Healthy Controls ◽  
Blood Monocytes ◽  
Monocyte Subsets ◽  
Oral Corticosteroids ◽  
Duration Of Disease ◽  
Classical Monocytes ◽  
Intermediate Monocytes

BackgroundIn sarcoidosis, blood monocytes, circulating precursors of granuloma macrophages, display enhanced inflammatory cytokine production, reduced expression of the regulatory (inhibitory) receptor CD200R, and altered subsets defined by CD14 and CD16. Regulatory receptors serve to dampen monocyte and macrophage inflammatory responses. We investigated the relationship between monocyte subsets and regulatory receptor expression in sarcoidosis.MethodsMulti-parameter flow cytometry was used to perform detailed analyses of cell surface regulatory molecules on freshly isolated blood immune cells from patients with chronic pulmonary sarcoidosis and age-matched healthy controls.ResultsTwenty-five patients with chronic pulmonary sarcoidosis (median duration of disease 22 months) who were not taking oral corticosteroids or other immunomodulators were recruited. Non-classical monocytes were expanded in sarcoidosis and exhibited significantly lower expression of regulatory receptors CD200R, SIRP-α, and CD47 than classical or intermediate monocytes. In sarcoidosis, all three monocyte subsets had significantly reduced CD200R and CD47 expression compared with healthy controls. A dichotomous distribution of CD200R was seen on classical and intermediate monocytes in the sarcoidosis population, with 14/25 (56%) sarcoidosis patients having a CD200R-low phenotype, and 11/25 (44%) CD200R-high. These distinct sarcoidosis monocyte phenotypes remained consistent over time.ConclusionNon-classical monocytes, which are expanded in sarcoidosis, express very low levels of regulatory receptors. Two distinct and persistent phenotypes of CD200R expression in classical and intermediate monocytes could be evaluated as sarcoidosis biomarkers.

scholarly journals 0009 Anti-Streptococcal Antibodies in Chinese Patients with Type -1 Narcolepsy

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A3-A4
Author(s):  
Q Ding ◽  
J Li ◽  
F Xiao ◽  
C Zhang ◽  
X Dong ◽  
...  
Keyword(s):  
Disease Duration ◽  
Streptococcal Infection ◽  
Chinese Patients ◽  
Healthy Controls ◽  
Recent Onset ◽  
Clear Cut ◽  
Streptolysin O ◽  
Environmental Trigger ◽  
Antibody Titers

Abstract Introduction Narcolepsy type 1 (NT1) is considered to be an autoimmune disease, and streptococcal infection may be an environmental trigger. However, previous studies from Asian narcolepsy patients did not reveal elevated anti-streptolysin O [ASO]. The aim is to investigate whether large sample Chinese patients with NT1 have an increase in antistreptococcal antibody titers. Methods A total of 214 narcolepsy patients and 360 healthy controls were recruited. All patients were DQB1*0602 positive with clear-cut cataplexy or had low CSF hypocretin-1. Participants were tested for ASO and anti DNAse B [ADB]. These patients were divided into five groups according to disease duration, including 29 patients less than 3 months; 25 from 3 months to 1 year; 40 from 1 to 3 years; 61 from 3 to 10 years and 59 patients over 10 years. Comparison was also made between children and adults with age matched controls, respectively. Results There were no significant differences between patients and healthy controls in regard to both ASO ≥ 200 IU (19.2% vs. 16.9%, p = 0.50) and ADB≥480IU (9.8% vs. 10.3%, p = 0.86). For children narcolepsy patients, ASO positive rates(19.8% vs. 18%, p = 0.68) and ADB positive rates(10.4% vs. 12%, p = 0.72) had no differences compared to age matched controls. And no difference was observed in adult narcolepsy patients either, with ASO positive rates (18.5% vs. 13.8%, p = 0.39) and ADB positive rates (9.3% vs. 5.3%, p = 0.42) compared to age matched controls, respectively. ASO (ADB) positive rates had no significant differences among different disease duration groups(p= 0.55, 0.9). Conclusion It is indicated that positive rates of ASO and ADB were not significantly different between Chinese patients with NT1 and healthy controls, including recent onset cases and children. Support The study was supported by the National Natural Science Foundation of China (No. 81420108002 and NO. 81570083)

Plasma thiol/disulphide homeostasis changes in patients with restless legs syndrome

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ertan Kucuksayan ◽  
Serkan Ozben ◽  
Selma Topaloglu Tuac ◽  
Mesrure Koseoglu ◽  
Ozcan Erel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Restless Legs Syndrome ◽  
Rating Scales ◽  
Spectrophotometric Analysis ◽  
Healthy Controls ◽  
Restless Legs ◽  
Severity Rating ◽  
Total Thiol ◽  
Disease Rating ◽  
Positive Correlations

Abstract Objectives Restless legs syndrome (RLS) is a common neurological condition. Oxidative stress plays an important role in its pathogenesis. Thiol-disulphide homeostasis (TDH) is a new biomarker of oxidative stress. We studied plasma TDH to determine whether TDH could be used as a new biomarker for RLS and evaluated correlations between TDH and various disease severity rating scales. Methods A total of 25 RLS patients and 25 healthy controls were included into the study. TDH status was determined using an automated spectrophotometric analysis method and correlations were analyzed between the TDH status and various disease rating scales in the RLS patients. Results Plasma total (401 ± 27 μmol/L) and native thiol (354 ± 30 μmol/L) levels were significantly lower, but disulphide level (24 ± 6 μmol/L) was significantly (<0.0001) higher in the RLS patients compared to the controls (455 ± 36, 424 ± 37, 15 ± 5 μmol/L, respectively). The disulphide/native thiol and disulphide/total thiol ratios increased, in contrast, native thiol/total thiol ratio decreased significantly in the RLS patients compared to the healthy controls (<0.0001). The disulphide levels correlated positively with age and various rating scores of the RLS patients. International Restless Legs Syndrome Study Group (IRLSSG) rating score and age correlated negatively with the total and native thiol levels. Conclusions Our findings indicate increased oxidative stress in the RLS patients reflected by decreased native and total thiol, and increased disulphide levels and positive correlations between the disulphide levels and various rating scores. We suggest dynamic TDH status to be used as a novel biomarker for the diagnosis and follow-up of the RLS patients.

Decreased Flow-Mediated Dilatation in Children With Type 1 Diabetes: A Systematic Review and Meta-Analysis

Angiology ◽  
2021 ◽  
pp. 000331972110100
Author(s):  
Lei Cao ◽  
Miao Hou ◽  
Wanping Zhou ◽  
Ling Sun ◽  
Jie Shen ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Type 1 Diabetes ◽  
Endothelial Function ◽  
Meta Analysis ◽  
Quality Data ◽  
Cochrane Library ◽  
Healthy Children ◽  
Healthy Controls ◽  
Flow Mediated Dilatation

Type 1 diabetes (T1DM) is a strong risk factor for the development of cardiovascular disease. Flow-mediated dilatation (FMD) is an early noninvasive marker of endothelial function and it predicts future cardiovascular disease. However, the changes in FMD among T1DM children are still controversial. The present meta-analysis aimed to investigate whether FMD is impaired in children with T1DM. PubMed, EMBASE, Cochrane library, and Web of Science were searched for studies comparing FMD in children with T1DM and healthy controls. The Newcastle-Ottawa quality assessment scale for case–control studies was used to assess study quality. Data were pooled using a random effects models to obtain the weighted mean differences (WMD) in FMD and 95% CIs. Overall, 19 studies with 1245 patients and 872 healthy controls were included in this meta-analysis. Children with T1DM had significantly lower FMDs compared with healthy controls (WMD: −2.58; 95% CI: −3.36 to −1.81; P < .001). Meta-regression analysis revealed that low-density lipoprotein cholesterol levels impacted the observed difference in FMD between T1DM and healthy children. This meta-analysis showed that T1DM children have impaired endothelial function, which indicates they are at higher risk of developing cardiovascular disease in later life.

scholarly journals A/H1N1 hemagglutinin antibodies show comparable affinity in vaccine-related Narcolepsy type 1 and control and are unlikely to contribute to pathogenesis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexander Lind ◽  
Ilaria Marzinotto ◽  
Cristina Brigatti ◽  
Anita Ramelius ◽  
Lorenzo Piemonti ◽  
...  
Keyword(s):  
Antibody Response ◽  
Antigenic Determinant ◽  
Etiological Agent ◽  
Healthy Controls ◽  
Antibody Affinity ◽  
Antibody Titres ◽  
Antibody Levels ◽  
And Control ◽  
Radiobinding Assay

AbstractAn increased incidence of narcolepsy type 1 (NT1) was observed in Scandinavia following the 2009–2010 influenza Pandemrix vaccination. The association between NT1 and HLA-DQB1*06:02:01 supported the view of the vaccine as an etiological agent. A/H1N1 hemagglutinin (HA) is the main antigenic determinant of the host neutralization antibody response. Using two different immunoassays, the Luciferase Immunoprecipitation System (LIPS) and Radiobinding Assay (RBA), we investigated HA antibody levels and affinity in an exploratory and in a confirmatory cohort of Swedish NT1 patients and healthy controls vaccinated with Pandemrix. HA antibodies were increased in NT1 patients compared to controls in the exploratory (LIPS p = 0.0295, RBA p = 0.0369) but not in the confirmatory cohort (LIPS p = 0.55, RBA p = 0.625). HA antibody affinity, assessed by competition with Pandemrix vaccine, was comparable between patients and controls (LIPS: 48 vs. 39 ng/ml, p = 0.81; RBA: 472 vs. 491 ng/ml, p = 0.65). The LIPS assay also detected higher HA antibody titres as associated with HLA-DQB1*06:02:01 (p = 0.02). Our study shows that following Pandemrix vaccination, HA antibodies levels and affinity were comparable NT1 patients and controls and suggests that HA antibodies are unlikely to play a role in NT1 pathogenesis.

scholarly journals A cross sectional study to compare cardiac structure and diastolic function in adolescents and young adults with youth-onset type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth Study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Amy S. Shah ◽  
Scott Isom ◽  
Dana Dabelea ◽  
Ralph D’Agostino ◽  
Lawrence M. Dolan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Diastolic Function ◽  
Healthy Controls ◽  
Cross Sectional ◽  
Factors Associated ◽  
Youth Study ◽  
Hispanic White ◽  
Diabetes In Youth

Abstract Aims To compare left ventricular structure (LV) and diastolic function in young adults with youth- onset diabetes by type, determine the prevalence of abnormal diastolic function by diabetes type using published values from age similar healthy controls, and examine the risk factors associated with diastolic function. Methods In a cross sectional analysis we compared LV structure and diastolic function from two dimensional echocardiogram in participants with type 1 (T1D) and type 2 diabetes (T2D) who participated in the SEARCH for Diabetes in Youth Study. Linear models were used to examine the risk factors associated with worse diastolic function. Results Of 479 participants studied, 258 had T1D (mean age 21.2 ± 5.2 years, 60.5% non-Hispanic white, 53.9% female) and 221 had T2D (mean age 24.8 ± 4.3 years, 24.4% non-Hispanic white, 73.8% female). Median diabetes duration was 11.6 years. Participants with T2D had greater LV mass index and worse diastolic function that persisted after adjustment for differences in risk factors compared with participants with T1D (all p < 0.05). Abnormal diastolic function, quantified using healthy controls, was pronounced in both groups but greater in those with T2D than T1D (T2D: 57.7% vs T1D: 47.2%, respectively), p < 0.05. Risk factors associated with worse diastolic function included older age at diabetes diagnosis, female sex, higher BP, heart rate and HbA1c and longer diabetes duration. Conclusions LV structure and diastolic function is worse in individuals with T2D compared to T1D. However, abnormal diastolic function in seen in both groups compared to published values from age similar healthy controls.

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