scholarly journals Elevated Serum Level of Cytokeratin 18 M65ED Is an Independent Indicator of Cardiometabolic Disorders

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Lingling Qian ◽  
Lei Zhang ◽  
Liang Wu ◽  
Jing Zhang ◽  
Qichen Fang ◽  
...  
Keyword(s):  
Cell Death ◽  
Regression Analysis ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cytokeratin 18 ◽  
Independent Manner ◽  
Nonalcoholic Fatty Liver ◽  
Cardiometabolic Disorders

Background. Recent studies have suggested that cell death might be involved in the pathophysiology of metabolic disorders. The cytokeratin 18 (CK18) fragment, as a cell death marker, plays an important role in nonalcoholic fatty liver disease (NAFLD). However, only a limited number of studies have found elevated serum levels of CK18 in patients with type 2 diabetes. Moreover, no studies have been conducted yet to investigate the role of CK18 in hypertension or dyslipidemia. In particular, CK18 M65ED is a more sensitive marker of cell death, and its role in cardiometabolic disorders has not been revealed yet. Methods. A total of 588 subjects were enrolled from the local communities of Shanghai. Serum CK18 M65ED were determined using the enzyme-linked immunosorbent assay. A cardiometabolic disorder was identified by the presence of at least one of the components including overweight or central obesity, diabetes, dyslipidemia, and hypertension. Results. Subjects with cardiometabolic disorders exhibited significantly higher serum levels of CK18 M65ED than those without cardiometabolic disorders (197.36 (121.13–354.50) U/L versus 83.85 (52.80–153.75) U/L, respectively, P<0.001). Increased serum CK18 M65ED quartiles were associated with the increased prevalence of cardiometabolic disorders and its components (P<0.001 for all components). Multiple stepwise regression analysis also revealed that diastolic blood pressure, glycated hemoglobin A1c, alanine transaminase, and high-density lipoprotein cholesterol were independently correlated with serum CK18 M65ED levels (all P<0.01). In addition, logistic regression analysis showed that the serum CK18 M65ED levels were positively correlated with cardiometabolic disorders and in an independent manner. Further, CK18 M65ED was revealed to be an indicator of cardiometabolic disorders in a NAFLD-independent manner. Conclusions. Elevated levels of CK18 M65ED, a sensitive cell death marker, were independently and positively correlated with cardiometabolic disorders, even after the adjustment for the presence of NAFLD and other cardiovascular risk factors.

P26 Soluble programed cell death ligand-1 is associated with acute coronary syndrome

2020 ◽  
Vol 41 (Supplement_1) ◽  
Author(s):  
K Fujisue ◽  
E Yamamoto ◽  
D Sueta ◽  
M Takae ◽  
T Nishihara ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Coronary Syndrome ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Serum Level ◽  
Plaque Rupture ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Coronary Syndrome ◽  
Stable Cad

Abstract Background Immune checkpoint by programmed cell death (PD)-1 and its ligand (PD-L1) play crucial role in T cell tolerance toward vascular wall antigens. PD-L1 is widely expressed on a number of cells including immune cells and vascular endothelium. It was reported that increased expression of PD-L1 in dendritic cells implicates upregulated inflammation in atherosclerotic lesions that is associated with plaque instability. Although plaque rupture in coronary atherosclerosis is an important pathogenesis of acute coronary syndrome (ACS), the association between PD-L1 and ACS is still unknown. Purpose We hypothesize that circulating PD-L1 might be associated with ACS, reflecting endothelial damage and coronary plaque rupture. To elucidate this hypothesis, we compared serum levels of soluble PD-L1 (sPD-L1) in stable coronary artery disease (CAD) patients with those in ACS patients. Methods Serum levels of sPD-L1 were measured by using commercially available ELISA kit (Human PD-L1/B7-H1 DuoSet, R&D Systems) in consecutive patients with CAD admitted to our University Hospital from February 2016 to March 2017. Patients with any malignant disease or severe inflammatory disease were excluded from this study. Serum levels of sPD-L1 and clinical backgrounds were compared between stable-CAD and ACS patients. Results In total, 269 patients with CAD were enrolled (28 cases [10.4 %] with ACS and 241 cases [89.6 %] with stable-CAD). PD-L1 had no correlation to C-reactive protein, cardiac troponin, and classical atherosclerotic risks such as age, body mass index, estimated glomerular filtration rate, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, and hemoglobin A1c. Although age, sex, history of smoking, and the prevalences of hypertension, diabetes mellitus and dyslipidemia were comparable between both groups, the level of LDL-C was significantly higher in patients with ACS compared with those with stable-CAD (94.0 [77.0–112.0] mg/dL vs. 78.5 [65.0–97.0] mg/dL, P = 0.008). Also serum level of sPD-L1 was significantly increased in patients with ACS compared with those with stable-CAD (106.1 [60.9–157.7] pg/mL vs. 64.8 [30.9–102.5] pg/mL, P = 0.003). Univariate logistic regression analysis identified that serum levels of both sPD-L1 and LDL-C were independently associated with ACS. Moreover, multivariable logistic regression analysis with factors from univariate analysis identified that serum level of sPD-L1 was significantly and independently associated with ACS (odds ratio: 1.006, 95 % confidence interval: 1.001–1.012, P = 0.03). Conclusions This is the first study to elucidate that the increased serum levels of sPD-L1 was associated with ACS. This study suggests that sPD-L1 could be a risk marker and therapeutic target for ACS.

The Relationship of Serum Hemojuvelin and Hepcidin Levels with Iron Overload in Nonalcoholic Fatty Liver Disease

2015 ◽  
Vol 24 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Salih Boga ◽  
Huseyin Alkim ◽  
Canan Alkim ◽  
Ali Riza Koksal ◽  
Mehmet Bayram ◽  
...  
Keyword(s):  
Liver Disease ◽  
Iron Overload ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Clinical Characteristics ◽  
Serum Levels ◽  
Fibrosis Stage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Nonalcoholic Fatty Liver

Background & Aims: Mild iron overload is frequently reported in patients with nonalcoholic fatty liver disease (NAFLD). Hepcidin is the master iron-regulatory peptide and hemojuvelin (HJV) is the key regulator of iron-dependent secretion of hepcidin. The aims of this study were to evaluate serum HJV and hepcidin levels in patients with biopsy-proven NAFLD with and without hepatic iron overload, and to identify potential associations of HJV and hepcidin with the clinical characteristics of the patients enrolled. Methods: Serum levels of HJV and hepcidin were measured in 66 NAFLD patients with (n=12) and without (n=54) iron overload, and controls (n=35) by enzyme-linked immunosorbent assay. Hemojuvelin and hepcidin levels were assessed in relation to clinical characteristics and liver histologic evaluation of the participants. Results: Significantly lower serum HJV (281.1 [239.2-353.6] vs. 584.8 [440.3-661] ng/ml, p<0.001) and similar serum hepcidin levels (60.5±31.1 vs. 55.8±11.9 ng/ml, p=0.285) were found in NAFLD patients when compared to controls. İron-overloaded NAFLD patients had significantly lower HJV (249.9 [187.6-296.3] vs. 292.9 [243-435] ng/ml, p=0.032) and significantly higher hepcidin (78.4±35.5 vs. 56.5±28.9ng/ml, p=0.027) levels than NAFLD patients without iron overload. Fibrosis stage was significantly higher in iron overloaded NAFLD group (p<0.001). Ferritin levels correlated significantly both with HOMA-IR (r=0.368, p=0.002) and fibrosis stage (r=0.571, p<0.001). Conclusions: Our findings suggest that HJV levels are low in NAFLD and even lower in iron overloaded NAFLD, while hepcidin levels are higher in NAFLD with iron overload. The gradually decreased HJV and increased hepcidin concentrations in our patients most likely reflect the physiological response to iron accumulation in the liver.

scholarly journals Sustained high expression of multiple APOBEC3 cytidine deaminases in systemic lupus erythematosus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Danielle Perez-Bercoff ◽  
Hélène Laude ◽  
Morgane Lemaire ◽  
Oliver Hunewald ◽  
Valérie Thiers ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Cell Death ◽  
Lupus Erythematosus ◽  
Immunosuppressive Treatment ◽  
Elevated Serum ◽  
Serum Levels ◽  
Chronic Inflammatory Disease ◽  
Mrna Levels ◽  
Systemic Lupus ◽  
Inflammatory Conditions

AbstractAPOBEC3 (A3) enzymes are best known for their role as antiviral restriction factors and as mutagens in cancer. Although four of them, A3A, A3B, A3F and A3G, are induced by type-1-interferon (IFN-I), their role in inflammatory conditions is unknown. We thus investigated the expression of A3, and particularly A3A and A3B because of their ability to edit cellular DNA, in Systemic Lupus Erythematosus (SLE), a chronic inflammatory disease characterized by high IFN-α serum levels. In a cohort of 57 SLE patients, A3A and A3B, but also A3C and A3G, were upregulated ~ 10 to 15-fold (> 1000-fold for A3B) compared to healthy controls, particularly in patients with flares and elevated serum IFN-α levels. Hydroxychloroquine, corticosteroids and immunosuppressive treatment did not reverse A3 levels. The A3AΔ3B polymorphism, which potentiates A3A, was detected in 14.9% of patients and in 10% of controls, and was associated with higher A3A mRNA expression. A3A and A3B mRNA levels, but not A3C or A3G, were correlated positively with dsDNA breaks and negatively with lymphopenia. Exposure of SLE PBMCs to IFN-α in culture induced massive and sustained A3A levels by 4 h and led to massive cell death. Furthermore, the rs2853669 A > G polymorphism in the telomerase reverse transcriptase (TERT) promoter, which disrupts an Ets-TCF-binding site and influences certain cancers, was highly prevalent in SLE patients, possibly contributing to lymphopenia. Taken together, these findings suggest that high baseline A3A and A3B levels may contribute to cell frailty, lymphopenia and to the generation of neoantigens in SLE patients. Targeting A3 expression could be a strategy to reverse cell death and the generation of neoantigens.

scholarly journals Correlation between HDL2, HDL3 and serum ferritin levels with fatty liver and NAFLD activity score (NAS) in liver histology of organ donors

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Saman Nikeghbalian ◽  
Rasoul Rahimi ◽  
Hamed Nikoupour ◽  
Neda Soleimani ◽  
Sina Vakili ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Serum Ferritin ◽  
Density Lipoprotein ◽  
Organ Donor ◽  
Serum Levels ◽  
Liver Histology ◽  
Activity Score ◽  
Organ Donors ◽  
Nonalcoholic Fatty Liver ◽  
Nafld Activity Score

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is one of the most important liver diseases. High-density lipoprotein (HDL) has anti-atherogenic properties and its reduction can be associated with fatty liver. Serum ferritin levels are usually elevated in patients with NAFLD. This study aimed to evaluate the correlation between HDL subtypes and serum ferritin levels with evidence of NAFLD in liver histology of organ donors. Methods One hundred organ donor patients who were eligible for the study were included in the study and ferritin; HDL2 and HDL3 were measured in blood samples. Donated liver tissue biopsy specimens were evaluated for fatty liver and NAFLD activity score (NAS). In addition, AST and ALT were measured in recipients 24 h after transplant. All data abstracted and analyzed statistically. Results Serum HDL2 levels and HDL2/HDL3 ratio in patients with NAS > 1 were significantly lower (P < 0.05). Serum levels of HDL3 and ferritin were not significantly associated with NAS >1 (P > 0.05). In addition, serum ferritin > 1000 ng/ml in organ donors associated with increased AST and ALT levels 24 h after transplantation in the liver organ recipient. Conclusions Lower HDL2 values and HDL2/HDL3 ratio were associated with increased NAFLD activity score, but HDL3 and ferritin did not show such a relationship. In addition, higher levels of ferritin in organ donors may be associated with increased AST and ALT 24 h after liver transplantation in the organ recipient.

ERYTHROFERRONE AS A NEW BIOMARKER ASSOCIATED WITH ANEMIA IN IRAQI PATIENTS WITH CKD

2021 ◽  
Vol 17 (37) ◽  
pp. 135-148
Author(s):  
Intisar Razzaq SHARBA ◽  
Hasanat Abdulrazzaq ALJABERY ◽  
Manal Farhan AL-KHAKANI
Keyword(s):  
Kidney Diseases ◽  
Transferrin Saturation ◽  
Elevated Serum ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Erythropoietic Activity ◽  
Glycoprotein Hormone ◽  
Hormone Synthesis ◽  
Gender And Age ◽  
Group 2

Background: Erythroferrone (ERFE) is a glycoprotein hormone synthesis and release by erythroblasts. Recently identified as an erythropoietic regulator and activated in response to stimulating erythropoietin (Epo). In chronic kidney diseases (CKD), anemia is a hallmark disorder due to a decrease in hyposensitive erythropoietic to the Epo; these patients recommended to use of Erythropoiesis-stimulating agents (ESAs). The aim: This study aimed to assess serum ERFE level in patients with CKD and investigate the continuing effects of long-term anemic ESA use associated with markers of erythropoiesis and iron metabolism. Methods: Sixty-five CKD patients divided in two groups, included 30 hemodialyses (HD) and 35 without hemodialysis (non-HD) CKD patients, were compared to 25 healthy voluntaries matched by gender and age enrolled in the current study. Serum ERFE level was measured by an enzyme-linked immunosorbent assay (ELISA). Results: Serum ERFE level was significantly elevated in HD patients median (IQR) about 17.25 (13.4) ng/mL, odds ratio (OR = 10.161), (AUC 0.996) greater than CKD 4(6.1) ng/ml, (OR = 6.295), (AUC = 0.984) p 0.001; also, these are positively correlated with the use of ESA in HD, and CKD (r = 1.00 and r = 0.95) respectively as compared to healthy group 2(2.1) ng/ml. Serum ERFE levels were significantly negative (p 0.05) in both CKD and HD patients related to GFR (r = -0.396, and r = -0.68), transferrin saturation (TS%) (r = -0.842, and r = -0.877), serum levels of Ferritin (r = -0.865 and r = -0.866), and Iron (r = -0.860, and r = -0.851), RBC (r = -0.841, and r = -0.843), hemoglobin (Hb) (r = -0.758, and r = -0.796). Conclusion: The present study demonstrated that elevated serum ERFE levels associated with erythropoietic activity and anemia are higher in CKD with HD and non -HD patients treated with ESA than in non-ESA patients. This study suggested using ERFE as a successful tool for erythropoietic activity inspection in CKD, especially those taking ESAs to treat anemia.

scholarly journals Hepatoprotective effect of aqueous extract of cardamom against gentamicin induced hepatic damage in rats

2015 ◽  
Vol 5 (1) ◽  
pp. 1 ◽  
Author(s):  
Mohamed Aboubakr ◽  
Abdelazem Mohamed Abdelazem
Keyword(s):  
Aqueous Extract ◽  
Histopathological Examination ◽  
Low Density Lipoprotein ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Hepatoprotective Activity ◽  
Lipoprotein Cholesterol ◽  
Albino Rats ◽  
Aqueous Extracts

<p>The study was designed to evaluate the hepatoprotective activity of aqueous extract of cardamom in acute experimental liver injury induced by gentamicin. Twenty four male albino rats were randomly divided into four groups (six rats in each). Animals of the first group served as control and orally (p.o.) received (1 ml/kg saline). The second experimental group was given gentamicin (80 mg/kg i.p.) for 7 days. Third and fourth groups were given aqueous extract of cardamom (100 and 200 mg/kg p.o.) + gentamicin for 7 days, respectively. The degree of hepatoprotection was measured using serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, albumin, and lipid profile levels. In the acute liver damage induced by gentamicin, cardamom aqueous extracts (100 and 200 mg/kg, p.o.) significantly reduced the elevated serum levels of AST, ALT, bilirubin, cholesterol, triglycerides and low density lipoprotein cholesterol (LDL-chol) in gentamicin induced hepatotoxicity. Also cardamom aqueous extracts (100 &amp; 200 mg/kg, p.o.) significantly increased the lowered serum levels of albumin and high density lipoprotein cholesterol (HDL-chol) in gentamicin induced hepatotoxicity rats. Histopathological examination of the liver tissues supported the hepatoprotection. Our findings concluded that cardamom aqueous extracts possessed hepatoprotective activity against gentamicin induced hepatotoxicity in rats.</p>

scholarly journals Th1, Th2, and Th17 Cytokine Involvement in Thyroid Associated Ophthalmopathy

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Jie Shen ◽  
Zhangfang Li ◽  
Wenting Li ◽  
Ying Ge ◽  
Min Xie ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Elevated Serum ◽  
Serum Levels ◽  
Thyroid Stimulating Hormone ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Necrosis Factor Alpha ◽  
Thyroid Associated Ophthalmopathy ◽  
Th17 Cytokines ◽  
Th17 Cytokine

To determine serum cytokine profiles in Graves’ disease (GD) patients with or without active and inactive thyroid associated ophthalmopathy (TAO), we recruited 65 subjects: 10 GD only (without TAO), 25 GD + active TAO, 20 GD + TAO, and 10 healthy controls. Liquid chip assay was used to measure serum Th1/Th2/Th17 cytokines including IFN-γ(interferon-gamma), TNF-α(tumor necrosis factor-alpha), IL-1α(interleukin-1 alpha), IL-1Ra (IL-1 receptor antagonist), IL-2, IL-4, IL-6, and IL-17 and two chemokines: RANTES (regulated upon activation, normal T cell expressed and secreted) and IP-10 (IFN-γ-induced protein 10). Serum levels of TSH (thyroid stimulating hormone) receptor autoantibodies (TRAb) were measured using an enzyme linked immunosorbent assay. Compared with healthy controls, TAO patients showed significantly elevated serum levels of IFN-γ, TNF-α, IL-1α, IL-4, IL-6, IL-17, and IP-10. Comparing active and inactive TAO, serum Th1 cytokines IFN-γand TNF-αwere elevated in active TAO, while serum Th2 cytokine IL-4 was elevated in inactive TAO. Serum Th17 cytokine IL-17 was elevated in GD but reduced in both active and inactive TAO. A positive correlation was found between TRAb and IFN-γ, TNF-α, IL-1α, IL-2, IL-4, and IL-6. Taken together, serum Th1/Th2/Th17 cytokines and chemokines reflect TAO disease activity and may be implicated in TAO pathogenesis.

scholarly journals The Association of Elevated Serum Lipocalin-2 Levels With Diabetic Peripheral Neuropathy in Type 2 Diabetes

2021 ◽  
Author(s):  
Xi Zhang ◽  
Xiurong Shen ◽  
Wan Zhou ◽  
Mengyun Xu ◽  
Yan Xing ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Regression Analysis ◽  
Peripheral Neuropathy ◽  
Diabetic Peripheral Neuropathy ◽  
Diastolic Pressure ◽  
Elevated Serum ◽  
Assay Method ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lipocalin 2

Abstract BackgroundA variety of studies have demonstrated the role of lipocalin-2 (LCN2) in both diabetes and neurological disorders. Nevertheless, the relationship between LCN2 and diabetic peripheral neuropathy (DPN) needs to be elucidated in humans. Therefore, this study was aimed to investigate the association of LCN2 with DPN in type 2 diabetes (T2D).MethodsA total 207 participants with T2D were included in this study. All participants were classified into DNP group and non-DNP (NDPN) group based on the Toronto Clinical Neuropathy Scoring (TCNS). Demographic and biochemical parameters were measured. Serum LCN2 levels were determined using an enzyme-linked immunosorbent assay method. ResultsSerum LCN2 levels in DNP group were higher than those in NDPN group (p = 0.001). Stratification analysis according to the tertiles of serum LCN2 levels showed that with the LCN2 level elevated, the number of participants with DPN increased, whereas the number of participants with NDPN decreased (trend p = 0.003). Moreover, serum LCN2 levels positively correlated to TCNS scores, which reflects neuropathy severity (r = 0.438, p = 0.000). Multivariate stepwise regression analysis showed that BMI, triglycerides and diastolic pressure were independently associated with serum LCN2 in DPN. Additionally, logistic regression analysis demonstrated that LCN2 (OR = 1.009) and diabetes duration (OR = 1.058) were independently associated with the occurrence of DPN in T2D.ConclusionsOur report reveals the association of serum LCN2 with DPN in T2D. LCN2 might be used to evaluate DPN severity and serve a role in the pathogenesis of DPN.

scholarly journals Elevated serum levels of checkpoint molecules in patients with adult Still’s disease

2020 ◽  
Author(s):  
Yuya Fujita ◽  
Tomoyuki Asano ◽  
Haruki Matsumoto ◽  
Naoki Matsuoka ◽  
Jumpei Temmoku ◽  
...  
Keyword(s):  
Disease Activity ◽  
Immunosuppressive Treatment ◽  
Elevated Serum ◽  
Serum Levels ◽  
Chronic Arthritis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Still’S Disease ◽  
Serum Samples ◽  
Still's Disease ◽  
Adult Still's Disease

Abstract Background: The interaction between galectin-9 (Gal-9) and its ligand, T cell immunoglobulin and mucin-containing-molecule-3 (TIM-3), one of the coinhibitory receptors, transduce the inhibitory signaling to regulate immune responses. The dysregulated expression of checkpoint molecules has been reported under various inflammatory or autoimmune conditions. The aim of this study is to investigate the levels of these checkpoint molecules and their associations between proinflammatory markers in patients with adult Still’s disease (ASD). Methods: Serum samples were collected from 47 patients with active ASD, 116 patients with rheumatoid arthritis (RA), and 37 healthy controls (HCs). Serum levels of Gal-9, soluble TIM-3 (sTIM-3), and IL-18 were determined using enzyme-linked immunosorbent assay (ELISA). Results were compared with clinical features of ASD. Results: Serum Gal-9 levels in patients with ASD (median: 21.57 ng/ml, interquartile range IQR [11.41–39.72]) were significantly higher compared to those in patients with RA (7.58 ng/ml, IQR [5.57–10.20] p < 0.001) as well as those in HCs (4.51 ng/ml, [IQR; 3.58–5.45], p < 0.001). Similarly, serum sTIM-3 levels in patients with ASD were significantly higher than those in patients with RA and HCs. Serum levels of Gal-9 or sTIM-3 showed positive correlations with IL-18 levels (Gal-9; r = 0.90, p< 0.001, sTIM-3; r = 0.78, p< 0.001) in patients with ASD. Serum levels of Gal-9 or sTIM-3 correlated with serum ferritin (Gal-9; r = 0.77, p< 0.001, sTIM-3; r = 0.71, p< 0.001) and ASD disease activity score (Pouchot’s score, Gal-9; r = 0.66, p< 0.001, sTIM-3; r = 0.59, p< 0.001). Whereas there was no significant correlation between serum Gal-9 or sTIM-3 and CRP. ASD patients with chronic arthritis phenotype had a significantly higher Gal-9/ferritin and sTIM-3/ferritin ratio than those without this phenotype. After immunosuppressive treatment, Gal-9 and sTIM-3 levels showed a significant decline in parallel to the disease activity scores. Conclusions: Serum levels of the coinhibitory checkpoint molecules were elevated and correlated with disease activity in patients with ASD. These coinhibitory checkpoint molecule may be implicated in the autoinflammatory process seen in ASD.

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