Increased anti-KIR4.1 antibodies in multiple sclerosis: Could it be a marker of disease relapse?

2014 ◽  
Vol 21 (5) ◽  
pp. 572-579 ◽  
Author(s):  
Livnat Brill ◽  
Lotem Goldberg ◽  
Arnon Karni ◽  
Panayiota Petrou ◽  
Oded Abramsky ◽  
...  

Background: Screening of putative autoimmune targets in multiple sclerosis (MS) revealed a proportion of patients carrying antibodies (Abs) against KIR4.1, a potassium channel that shares functional properties with AQP4. Both are localized at the perivascular astrocytic processes. Aims: To measure anti-KIR4.1 Abs in the serum of MS and neuromyelitis optica (NMO) patients, and to identify the clinical and laboratory characteristics of patients harboring anti-KIR4.1 Abs. Methods: We measured anti-KIR4.1 Abs in serum, using the peptide KIR4.1 (83–120) enzyme-linked immunosorbent assay (ELISA). Results: Serum levels of anti-KIR4.1 Abs were significantly higher in MS and NMO patients than in healthy controls (HCs); with Abs detected in 21 of 80, 10 of 45, and 2 of 32 individuals, respectively (MS versus HC, p < 0.05). The level of anti-KIR4.1 Abs was significantly higher during MS relapse, versus remission ( p = 0.04). The clinical characteristics of our study patients did not vary based on KIR4.1 positivity. Conclusions: Anti-KIR4.1 Abs were found in similar proportions of patients with MS and NMO, at a significantly higher level than observed in HCs; consequently, the presence of Abs does not discriminate between these demyelinating diseases. However, anti-KIR4.1 Ab levels differed in MS patients during relapse and remission; as such, they may represent a marker of disease exacerbation.

2014 ◽  
Vol 20 (13) ◽  
pp. 1699-1703 ◽  
Author(s):  
Elodie Nerrant ◽  
Céline Salsac ◽  
Mahmoud Charif ◽  
Xavier Ayrignac ◽  
Clarisse Carra-Dalliere ◽  
...  

Background: auto-antibodies against the potassium channel inward rectifying potassium channel 4.1 (Kir4.1) have previously been identified in 46% of patients with multiple sclerosis (MS). Objectives: to confirm these findings. Methods: we evaluated the presence of anti-Kir4.1 antibodies by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence in 268 MS patients, 46 patients with other neurological diseases (OND) and 45 healthy controls. Results: anti-Kir4.1 antibodies were found in 7.5% of MS patients, 4.3% of OND patients and 4.4% of healthy controls. Immunofluorescence analysis did not identify any specific staining. Conclusions: we confirmed the presence of anti-Kir4.1 antibodies in MS patients, but at a much lower prevalence than previously reported.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ruyahan Huo ◽  
Heng Liu ◽  
Jing Chen ◽  
Hong Sheng ◽  
Li Miao

Abstract Background This study aims to investigate clinical significance of HMGB1 in neonatal patients with necrotizing enterocolitis (NEC). Methods This observational study enrolled a total of 106 stage II-III NEC neonatal patients, who were admitted in our hospital from March 2014 to March 2019. In addition, 99 suspected NEC patients and 200 healthy controls were included. The serum levels of HMGB1, I-FABP, and inflammatory factors CRP, IL-1β, IL-6 and TNF-α were determined by enzyme-linked immunosorbent assay (ELISA). Then, the demographic data and clinical characteristics of all patients were collected. Statistical analysis was conducted to determine the correlation between HMGB1 and the clinical characteristics. Results No significant difference was found in the basic characteristics of NEC patients and healthy controls, except for birth weight and gestational age. The expression levels of HMGB1, I-FABP, and inflammatory factors IL-1β, IL-6 and TNF-α were significantly higher in NEC patients, when compared to healthy controls. The serum levels of HMGB1, I-FABP, IL-1β and IL-6 markedly increased in stage II-III NEC patients, when compared to stage I NEC patients. The Pearson’s analysis revealed a positive correlation between HMGB1 and I-FABP, HMGB1 and IL-1β, and HMGB1 and IL-6. The ROC curve revealed that both HMGB1 and I-FABP can potentially be used as diagnostic factors for NEC. The logistic multivariate regression revealed that I-FABP, IL-1β and IL-6 are independent risk factors for mortality in neonatal NEC patients. Conclusions Serum HMGB1 levels are upregulated in neonatal NEC patients, and these are correlated with the patient’s prognosis.


2015 ◽  
Vol 24 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Salih Boga ◽  
Huseyin Alkim ◽  
Canan Alkim ◽  
Ali Riza Koksal ◽  
Mehmet Bayram ◽  
...  

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.


2018 ◽  
Vol 46 (9) ◽  
pp. 3970-3978 ◽  
Author(s):  
Shujun Guo ◽  
Qingqing Chen ◽  
Xiaoli Liang ◽  
Mimi Mu ◽  
Jing He ◽  
...  

Objective To investigate levels of regulatory B (Breg) cells, plasma cells, and memory B cells in the peripheral blood, and interleukin (IL)-10 in the serum of multiple sclerosis (MS) patients, and to determine the correlation between Breg cell levels and the Expanded Disability Status Scale (EDSS) score. Methods Levels of Breg cells, plasma cells, and memory B cells in the peripheral blood of 12 MS patients were measured using flow cytometry. IL-10 serum levels were measured by enzyme-linked immunosorbent assay. The correlation between Breg cell levels and MS EDSS score was measured using Pearson’s correlation coefficient. Results Compared with healthy controls, MS patients had decreased levels of CD19+CD24hiCD38hi Breg cells in their peripheral blood and reduced serum levels of IL-10; however, the ratios of CD19+CD27hiCD38hi plasma cells and CD19+CD27+CD24hi memory B cells to total B cells did not differ significantly between healthy controls and MS patients. CD19+CD24hiCD38hi Breg cell levels in the peripheral blood of MS patients were not significantly correlated with MS EDSS score. Conclusion Peripheral blood CD19+CD24hiCD38hi Breg cell levels and serum IL-10 levels were reduced in MS patients compared with controls, but Breg cell levels were not correlated with MS EDSS score.


2020 ◽  
Author(s):  
Yuto Tamura ◽  
Tamihiro Kawakami ◽  
Yupeng Dong ◽  
Miku Yoshinari ◽  
Yuka Nishibata ◽  
...  

Abstract Objective. It was previously demonstrated that cutaneous vasculitis, including IgA vasculitis and cutaneous arteritis (CA), is associated with the presence of IgM antibodies (Abs) against the phosphatidylserine/prothrombin complex (PS/PT). Recently, novel enzyme-linked immunosorbent assay kits for the detection of IgG and IgM anti-PS/PT (aPS/PT) Abs have become commercially available.Methods. The prevalence of serum IgG and IgM aPS/PT Abs in both cutaneous and systemic vasculitis was determined using these kits. In addition, to examine whether aPS/PT Abs were involved in the pathogenesis of cutaneous vasculitis, inbred wild-type rats were intravenously administered with a rat IgM class aPS/PT monoclonal Ab established previously or with rat immunoglobulins as controls. To express PS on the surface of vascular endothelium, these rats were given a subcutaneous injection of cell-free histones (250 µg/ml, 300 µl/site) 2 hours in advance. Results. Serum IgM aPS/PT Ab levels were elevated in patients with systemic vasculitis with skin involvement and CA compared to those in patients with systemic vasculitis without skin involvement and healthy controls. There was no significant difference in the serum levels of IgG aPS/PT Abs between the patients and healthy controls. Correspondingly, inbred wild-type rats intravenously administered with the aPS/PT monoclonal IgM Ab after appropriate priming—subcutaneous histone injection—developed cutaneous vasculitis. Some rats given rat IgM instead of the aPS/PT monoclonal Ab also developed cutaneous vasculitis, whereas vasculitis did not occur in rats given IgG or only priming by histones. Conclusion. IgM aPS/PT Abs could be involved in the pathogenesis of cutaneous vasculitis.


2008 ◽  
Vol 193 (4) ◽  
pp. 338-339 ◽  
Author(s):  
Yasuhide Iwata ◽  
Kenji J. Tsuchiya ◽  
Sumiko Mikawa ◽  
Kazuhiko Nakamura ◽  
Yoshifumi Takai ◽  
...  

SummaryImmune dysfunction has been proposed as a mechanism for the pathophysiology of autistic-spectrum disorders. The selectin family of adhesion molecules plays a prominent role in immune/inflammatory responses. We determined the serum levels of three types of soluble-form selectin (sP, sL and sE) in 15 men with high-functioning autism and 22 age-matched healthy controls by enzyme-linked immunosorbent assay. Levels of sP-selectin and sL-selectin were significantly lower in patients than in controls. Furthermore, sP-selectin levels were negatively correlated with impaired social development during early childhood.


2010 ◽  
Vol 16 (7) ◽  
pp. 883-887 ◽  
Author(s):  
Massimiliano Castellazzi ◽  
Carmine Tamborino ◽  
Alice Cani ◽  
Elena Negri ◽  
Eleonora Baldi ◽  
...  

Cerebrospinal fluid and serum levels and intrathecal synthesis of anti-Epstein—Barr virus (EBV) IgG were measured by enzyme-linked immunosorbent assay in 80 relapsing—remitting multiple sclerosis patients grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. Eighty patients with other inflammatory neurological disorders (OIND) and 80 patients with non-inflammatory neurological disorders (NIND) served as neurological controls. Cerebrospinal fluid concentrations were higher in OIND than in multiple sclerosis ( p < 0.0001) and NIND ( p < 0.01) for anti-viral-capsid-antigen (anti-VCA) IgG, in multiple sclerosis than in NIND ( p < 0.01) and in OIND than in NIND ( p < 0.05) for anti-EBV nuclear antigen-1 (EBNA-1) IgG. Serum levels were more elevated in OIND than in multiple sclerosis ( p < 0.05) and in MRI inactive than in MRI active multiple sclerosis ( p < 0.0001) for anti-VCA IgG, and in multiple sclerosis than in OIND and NIND ( p < 0.01) for anti-EBNA-1 IgG. Serum titres of anti-VCA and anti-EBNA-1 IgG were also positively ( p < 0.05) and inversely ( p < 0.001) correlated, respectively, with the Expanded Disability Status Scale. An intrathecal IgG production of anti-VCA and anti-EBNA-1 IgG, as indicated by Antibody Index, was present only in a limited number of multiple sclerosis patients and controls (range from 1.3 to 6.3%). These findings do not support a direct pathogenetic role of EBV-targeted humoral immune response in multiple sclerosis.


2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Jiali Wu ◽  
Lagu He ◽  
Le Bai ◽  
Li Tan ◽  
Min Hu

Objective. IgA vasculitis (lgAV) is the most frequent vessel vasculitis in children, and the prognosis is related to the children’s age and degree of nephritis. This study is aimed at investigating serum apolipoprotein M (apoM) levels in patients with lgAV patients and at evaluating the association between apoM and disease severity. Methods. A total of 109 lgAV patients and 76 age- and sex-matched healthy controls were included. The age and gender of the study participants were matched. ApoM levels were measured by an enzyme-linked immunosorbent assay. Additionally, the serum levels of lipids, apolipoproteins, kidney biochemical profiles, immunoglobulins (IgA, IgG, IgM, and IgE), and the complements (C3 and C4) were assessed using an automatic biochemical analyzer. Results. ApoM was increased significantly in lgAV patients compared to healthy controls. ApoM, meanwhile, was lower in patients with nephritis than in those without nephritis. The apoM levels were higher in classes I and II IgA vasculitis nephritis (lgAVN) patients than in classes III and IV. Besides, the apoM serum level<24.81 mg/L was an independent predictive factor for lgAVN and can be independently associated with the presence of nephritis in lgAV patients. Meanwhile, the serum apoM concentration negatively correlated with the ISKDC grading score in lgAVN patients. Conclusions. Serum apoM was elevated in lgAV patients and decreased gradually with the ISKDC grading score. ApoM (OR=0.32, 95%CI=0.12‐0.85, p=0.023) was identified as a protective factor for nephritis in all lgAV patients.


2019 ◽  
Vol 20 (6) ◽  
pp. 1400 ◽  
Author(s):  
Leila Motlagh Scholle ◽  
Diana Lehmann ◽  
Pushpa Joshi ◽  
Stephan Zierz

Fibroblast growth factor 21 (FGF-21) is known to be a biomarker for mitochondrial disorders. An upregulation of FGF-21 in serum and muscle of carnitine palmitoyltransferase I (CPT I) and carnitine palmitoyltransferase II (CPT II) knock-out mice has been reported. In human CPT II deficiency, enzyme activity and protein content are normal, but the enzyme is abnormally regulated by malonyl-CoA and is abnormally thermolabile. Citrate synthase (CS) activity is increased in patients with CPT II deficiency. This may indicate a compensatory response to an impaired function of CPT II. In this study, FGF-21 serum levels in patients with CPT II deficiency during attack free intervals and in healthy controls were measured by enzyme linked immunosorbent assay (ELISA). The data showed no significant difference between FGF-21 concentration in the serum of patients with CPT II deficiency and that in the healthy controls. The results of the present work support the hypothesis that in muscle CPT II deficiency, in contrast to the mouse knockout model, mitochondrial fatty acid utilization is not persistently reduced. Thus, FGF-21 does not seem to be a useful biomarker in the diagnosis of CPT II deficiency.


2020 ◽  
Vol 55 (4) ◽  
pp. 391-394
Author(s):  
Abhishek Chaturvedi ◽  
Guruprasad Rao ◽  
Samir Kumar Praharaj ◽  
Kanive Parashiva Guruprasad ◽  
Vivek Pais

Abstract Aim Chronic alcohol consumption can activate and dysregulate the neuroimmune system which leads to neuroinflammation. Neuroimmune regulatory proteins (NIReg) (e.g. Cluster of Differentiation 200 (CD200)) are the regulators of innate immune response and are responsible for silencing the innate immunity and suppression of inflammation. In this study, we explored the changes of serum levels of CD200 in patients with alcohol dependence at baseline, after one-week alcohol withdrawal and after one-month of alcohol abstinence. Methods Seventeen patients with alcohol dependence admitted for de-addiction treatment and 12 healthy controls were enrolled in the study. Blood samples were collected at baseline, after one-week, and after one-month, and CD200 levels were measured using enzyme-linked immunosorbent assay kit and compared with the healthy controls. Results The serum level of the neuroimmune regulatory protein CD200 in alcohol dependent group (at baseline) was significantly lower compared to healthy controls (p=0.003), and increased after one-week, and one-month period. Conclusion The present study indicates that decrease of CD200 serum levels in alcohol dependent patients and its rise during alcohol withdrawal and abstinence may provide a preliminary evidence of the role of neuroimmune regulatory proteins in neuroadaptation during alcohol withdrawal.


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