scholarly journals Association of HMGB1, S100A12 and IL-17A Expression with Immunoglobulin-Resistant in Kawasaki Disease and the Comparisons Between Different Adjunctive Therapeutic Approaches

Author(s):  
Yang Zhou ◽  
Liu Pan ◽  
You-jun Yang ◽  
Shi-yu Li ◽  
Wei Yin ◽  
...  

Abstract Objective: The DAMPs such as HMGB1, S100A12 and IL-17A have been reported to predict poor response to IVIG. The aim of this study was to analyze the role of HMGB1,S100A12 and IL-17A in the detection of inflammation in KD patients with IVIG-resistant, and to investigate the value of different adjunctive therapy.Method: This study enrolled 126 patients diagnosed with KD, as well as age-matched 16 febrile control subjects. The demographic or clinical data, laboratory parameter and blood sample were collected. Various laboratory parameters as predictive factors for IVIG-resistant were calculated. And the serum levels of IL-17A and mRNA expression levels of HMGB1 and S100A12 were tested in all patients. For patients with acute KD in IVIG-resistant, we studied the levels of laboratory variables when using of IVIG retreatment, methylprednisolone, infliximab for children patients. Result: The variance of laboratory parameters between the febrile control group and KD group were analyzed. Regarding laboratory parameters, KD individuals were found to have lower levels of L%, PA, CD4+, CD8+ and higher levels of WBC, N%, CRP, ESR, NT-proBNP, ALT, CD4+/CD8+ (P<0.05 or P<0.01). For KD group, the 53 IVIG-resistant patients had significantly higher levels of blood S100A12, HMGB1, serum IL-17A levels And N%, CRP, NT-pro BNP, TBIL, ALT, AST and lower levels of L%, PLT (P<0.05 or P<0.01) in comparison to the IVIG-responsive patients. For patients with acute KD in IVIG-resistant, after initial IVIG-treatment, the adjunctive therapy of IVIG, methyl prednisolone or infliximab were used, the inflammatory symptoms and laboratory inflammatory markers were improved when treated with those drugs. Conclusion: IVIG-resistant was associated with higher levels of HMGB1, S100A12, IL-17A, CRP, NT-pro BNP, TBIL, ALT, AST and lower levels of L%, PLT before IVIG, especially when combined, were useful predictors for IVIG-resistant in KD. In addition, the adjunctive therapy of methylprednisolone and infliximab showed more effective in relief clinical symptoms than IVIG retreatment.

2020 ◽  
Author(s):  
Deying Liu ◽  
Pan Liu ◽  
Fan Liu ◽  
Wei Yin ◽  
Yan Ding

Abstract Background: Kawasaki disease (KD) is a medium vessel vasculitis of unknown aetiology that predominantly affecting coronary arteries. The damage-associated molecular pattern molecules (DAMPs) such as HMGB1, S100A12 and IL-17A have been reported to predict poor response to IVIG. Here, we explored the the role of HMGB1, S100A12 and IL-17A in the detection of intravenous immunoglobulin (IVIG)-resistant in KD patients, and to investigate the value of different adjunctive therapy.Method: 126 KD patients and as well as age- and sex-matched 16 febrile control subjects were enrolled in our study. The fresh peripheral blood were collected from KD patients and febrile controls, analyzed the demographic or clinical data and various laboratory parameters. We also measured changes in serum levels of IL-17A and mRNA expression levels of HMGB1 and S100A12 were tested in IVIG-resistant KD patients. Further we explored the association between coronary arteries lesions and different treatment options about IVIG retreatment, methylprednisolone and infliximab for IVIG-resistant KD patients. Result: Regarding laboratory parameters, KD individuals were found to have lower levels of lymphocyte(L)%, prealbumin, CD4+, CD8+ and higher levels of WBC, neutrophil (N)%, CRP, ESR, NT-proBNP, ALT, CD4+/CD8+ (P<0.05 or P<0.01). For KD group, the 53 IVIG-resistant patients had significantly higher levels of S100A12, HMGB1, serum IL-17A, N%, CRP, NT-proBNP, TBIL, ALT, AST and lower levels of L%, PLT (P<0.05 or P<0.01) in comparison to the IVIG-responsive patients. For patients with IVIG-resistant, IVIG retreatment, methylprednisolone or infliximab were used. Methylprednisolone showed better in improving clinical symptoms and CRP than the IVIG retreatment and infliximab (P> 0.05).Conclusion: IVIG-resistant was associated with overreaction of inflammation.The levels of HMGB1,S100A12 and IL-17A suggested to be reliable predictors for IVIG-resistant in KD. In addition, the adjunctive therapy of methylprednisolone and infliximab showed more effective in relieving clinical symptoms than IVIG retreatment.


Author(s):  
Magdalena Londzin-Olesik ◽  
Beata Kos-Kudla ◽  
Jacek Karpe ◽  
Aleksandra Nowak ◽  
Mariusz Nowak

Abstract Background and Study Aims Thyroid-associated orbitopathy, the most common extrathyroidal manifestation of Graves’ disease, is an autoimmune inflammation of orbital soft tissue. We report the study assessing the effect of immunosuppressive treatment with methylprednisolone on selected antioxidant parameters in patients with Graves’ disease with active thyroid-associated orbitopathy. Patients and Methods Activity and serum levels of selected antioxidant parameters as well as lipid peroxidation products were determined in a group of 56 patients with active thyroid-associated orbitopathy at three time-points: at baseline, after the discontinuation of intravenous methylprednisolone treatment and at 3 months after the discontinuation of additional oral methylprednisolone treatment. A control group consisted of 20 healthy age- and sex-matched volunteers. Results We found an increased activity of superoxide dismutase and glutathione peroxidase and increased serum levels of uric acid, malondialdehyde and conjugated dienes, as well as a reduced activity of paraoxonase-1 and reduced serum vitamin C level in the study group at baseline. Systemic intravenous and oral methylprednisolone therapy led to normalization of activity and concentration of the most studied parameters. Conclusion Results of our study confirmed that oxidative stress is one of the factors involved in the pathogenesis of thyroid-associated orbitopathy and the methyloprednisolone treatment is effective in reducing both clinical symptoms and oxidative stress in patients with this disease.


BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhila Maghbooli ◽  
Abdorreza Naser Moghadasi ◽  
Nasim Rezaeimanesh ◽  
Abolfazl Omidifar ◽  
Tarlan Varzandi ◽  
...  

Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) is associated with inflammatory mediators that may also trigger downstream signaling pathways leading to reduce insulin sensitivity. Methods We aimed to determine the risk association of hyperinsulinemia in NMOSD patients with seropositive AQP4-IgG and the serum levels of interleukin (IL)-6 and IL-17A compared with the control group. Serum levels of metabolic (Insulin, Fasting Blood Sugar (FBS), lipid profile) and inflammatory (IL-6 and IL-17) markers were assessed in 56 NMOSD patients and 100 controls. Results Hyperinsulinemia was more prevalent in NMOSD patients independent of age, sex and body mass index (BMI) (48.2% vs. 26%, p = 0.005) compared to control group. After adjusting age, sex and BMI, there was significant association between lower insulin sensitivity (IS) and NMOSD risk (95% CI: Beta = 0.73, 0.62 to 0.86, p = 0.0001). Circulating levels of IL-6 and IL-17 were higher in NMOSD patients, and only IL-6 had an effect modifier for the association between lower insulin sensitivity and NMOSD risk. Conclusions Our data suggests that inflammatory pathogenesis of NMOSD leads to hyperinsulinemia and increases the risk of insulin resistance.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aleksandra Rajewska-Rager ◽  
Monika Dmitrzak-Weglarz ◽  
Pawel Kapelski ◽  
Natalia Lepczynska ◽  
Joanna Pawlak ◽  
...  

AbstractMood disorders have been discussed as being in relation to glial pathology. S100B is a calcium-binding protein, and a marker of glial dysfunctions. Although alterations in the S100B expression may play a role in various central nervous system diseases, there are no studies on the potential role of S100B in mood disorders in adolescents and young adults . In a prospective two-year follow-up study, peripheral levels of S100B were investigated in 79 adolescent/young adult patients (aged 14–24 years), diagnosed with mood disorders and compared with 31 healthy control subjects. A comprehensive clinical interview was conducted which focused on clinical symptoms and diagnosis change. The diagnosis was established and verified at each control visit. Serum S100B concentrations were determined. We detected: lower S100B levels in medicated patients, compared with those who were drug-free, and healthy controls; higher S100B levels in a depressed group with a family history of affective disorder; correlations between age and medication status; sex-dependent differences in S100B levels; and lack a of correlation between the severity of depressive or hypo/manic symptoms. The results of our study indicate that S100B might be a trait-dependent rather than a state-dependent marker. Due to the lack of such studies in the youth population, further research should be performed. A relatively small sample size, a lack of exact age-matched control group, a high drop-out rate.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1093.1-1093
Author(s):  
G. Pellegrino ◽  
K. Stefanantoni ◽  
F. Facioni ◽  
C. Angelelli ◽  
A. Gigante ◽  
...  

Background:Electrocardiographic (ECG) abnormalities are described in 25-75% Systemic Sclerosis (SSc) cases and they are associated with other systemic manifestations as well as with a worse prognosis. There is an increasing need for clinical and laboratory biomarkers to ameliorate the diagnostic and therapeutic approaches to patients with ECG abnormalities, due to their actual low sensitivity and specificity. Adipokines are circulating proteins that appear dysregulated in SSc and leptin in particular is synthesized in response to inflammatory conditions and seems to play a proinflammatory and pro-fibrotic action in SSc. Interesting, many studies in the last years have underlined its role in the cardiac remodeling mechanisms and in the development of cardiac fibrosis in other chronic diseases.Objectives:Aim of our study is to evaluate the role of leptin in the development of cardiac rhythm disorders (CRD) during SSc. Furthermore, by the analysis of the clinical and demographical parameters of our SSc patients, we tried to define other possible features associated with increased serum leptin concentration.Methods:We included eighty-five SSc patients, fulfilling the 2013 ACR/EULAR classification criteria, attending the Regional Rare Disease Center of Policlinico Umberto I of Rome. Fifty presented significant CRD at non-invasive diagnostic techniques (12 Lead ECG, 24-hour Holter ECG). Demographic, clinical, conventional cardiovascular risk factors were examined; instrumental and laboratory assessments were obtained, together with ECG recordings. Thirty-five SSc patients without pathologic finding at ECG traces, matched for demographic and clinical features, were recruited as the control group. In all cases, after obtaining written informed consent, blood samples were taken to measure serum levels of leptin using an ELISA assay (Life Technologies-Italia).Results:The fifty SSc patients with CRD (mean age 51±15 years; F:M 41:9) had pulmonary fibrosis (PF) in 32 cases (64%) and a BMI >25Kg/m2in 22 (44%) while in the control group of thirty-five SSc patients (mean age 49±16 years; F:M 33:2) PF was found in 15 (43%) and a BMI >25Kg/m2in 9 (35%); We detected significantly higher median values of serum leptin in SSc patients with CRD compared to the control group (12027 pg/ml IQR 12314 versus 6392 pg/ml IQR 7103;p 0,0009). Additionally, SSc patients with a BMI> 25 kg/m2(31 cases) as well as those with PF (47 cases) showed a significantly higher median serum leptin levels compared to those with BMI <25 kg/m2(13161 pg/ml IQR 13610 versus 8187 pg/ml IQR 8255;p 0,0008) and those without PF (11740 pg/ml IQR 11940 versus 7616 pg/ml IQR 7855;p 0,0079).Conclusion:To our knowledge this is the first report on high serum levels of leptin in SSc patients with CRD that also confirms its increase in those cases with a BMI >25 kg/m2and with PF, according to scientific literature data. The role of leptin in the pathogenesis of SSc remains unclear although it is already known its involvement in the development of cardiac fibrosis during other chronic diseases. On the basis of these results we speculate on leptin involvement in the pathogenesis of CRD during SSc, although further studies are needed with larger cohort of patients.References:[1]Vacca A et al. Rheumatology, 2014[2]Tyndall AJ et al. Ann Rheum Dis, 2010[3]Muresan L et al. Iran J Pub Health, 2017[4]Sanna T et al. Indian Pacing Electrophysiol J, 2009[5]Riccieri V et al. Clin Exp Rheumatol, 2011[6]Żółkiewicz J et al. Arch Dermatol Res, 2019[7]Huby AC et al. Circulation, 2015[8]Shulze PC et al. Clin Chim Acta, 2005[9]Van de Hoogen F et al. Arthritis Rheum, 2013[10]Gui X et al. Biochem Biophys Res Commun, 2018Disclosure of Interests:Greta Pellegrino: None declared, Katia Stefanantoni Consultant of: ItalfarmacoBoehringer Ingelheim, Fausta Facioni: None declared, Carlotta Angelelli: None declared, Antonietta Gigante: None declared, Roberto Badagliacca: None declared, Carmine Dario Vizza: None declared, Sergio Morelli: None declared, Edoardo Rosato: None declared, Valeria Riccieri: None declared


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. Lombardo ◽  
A. Vigezzi ◽  
G. Ietto ◽  
C. Franchi ◽  
V. Iori ◽  
...  

AbstractPatients afflicted with melanoma show lower vitamin D serum levels (VDSL) than the healthy population. This hypothesis agrees with its well-known antiproliferative features. An observational study was carried out to collect VDSL in patients suffering from melanoma. Our aim was to identify a potential connection between low VDSL and the risk to incur melanoma. Furthermore, we studied the association between VDSL at the diagnosis of melanoma and other germane prognostic factors. The population held in regard was composed of 154 patients with a diagnosis of melanoma between 2016 and 2019. These patients were retrospectively collected from our follow-up storage. We compared VDSL to clinical and pathological parameters (age, sex, tumour location, Breslow’s depth, Clark’s level, histological subtype, ulceration, et aliqua). Moreover, we recruited a control group with negative melanoma history. Mean and median of VDSL were significantly lower in the melanoma group. Instead, we found a negative association between melanoma and VDSL > 30 ng/L (OR 0.11; p < 0.0001). No correlation between VDSL and both Breslow’s depth and Clark’s level was discovered, but the VDSL comparison between thin (depth ≤ 1 mm) and thick tumours (depth > 1 mm) revealed a statistically significant difference (21.1 ± 8.2 ng/L vs 17.8 ± 8.1; p = 0.01). Moreover, VDSL were significantly lower in melanomas with mitotic rate ≥ 1/mm2 (22.1 ± 8.3 ng/L; p < 0007). Nevertheless, no connection was found between VDSL and both ulceration and positive sentinel nodes (p = 0.76; p = 0.74). Besides, our study revealed no association between VDSL and histological subtype (p = 0.161). Lower VDSL correlate with thick and high mitotic rate tumours. Future prospective studies would investigate if appropriate upkeep of suitable VDSL can decrease the risk of primary and recurrent melanoma diagnosis.


2021 ◽  
Vol 3 (2) ◽  
pp. 35-39
Author(s):  
Ferhan Kerget ◽  
Buğra Kerget ◽  
Alperen Aksakal ◽  
Abdullah Osman Koçak

Background: SARS-CoV-2 (Covid-19) pandemic which was firstly identified in Wuhan/China in December 2019.There still exists no precise treatment for this pandemic yet despite many agents are tried in prophylaxis and treatment for Covid-19. In this study, we aimed to investigate the efficacy of 2-aticyto complex in clinical course in these patients. Materials and Methods: 150 patients who applied to the Infection Diseases Polyclinics between dates September 2020-November 2020 having diagnosed with Covid-19 were included in our study. The patients were randomized into 2 groups (75 in each group) of which the first group only had the treatment of National Guideline and the second group had Viruthol® including 2-aticyto complex (at the dose of 27000 mcg/day) in addition to the treatment of the National Guideline. The laboratory parameters, clinical outcomes and the first day on which PCR result turned into negative of the patients were compared. Results: In Viruthol® group, LDH, CRP, D-Dimer and ferritin levels were significantly decreased compared to the control group, while lymphocyte levels were higher. (p=0.02, p=0.001, p=0.01, p=0.02, p=0,001 respectively).  In addition to that, clinical symptoms such as fever, headache, weakness, loss of taste and smell and muscle-joint pain recovered more rapidly in contrast with the control group (p=0.001, p=0.05, p=0.001, p=0.001, p=0.001, respectively). PCR results of the Viruthol® group turned negative in a statistically significant shorter period of time with respect to the control group (p=0.001). Conclusion: Viruthol® containing 2-aticyto complex may be an agent that can be used both symptomatic treatment and improving the clinical situation and recovery of the patients followed up for Covid-19.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Claudia Curci ◽  
Fabio Sallustio ◽  
Nada Chaoul ◽  
Angela Picerno ◽  
Gabriella Lauriero ◽  
...  

Abstract Background and Aims The IgA nephropathy (IgAN) is the most frequent primitive glomerulonephritis. In the last years, the role of mucosal immunity in IgAN, together with that of the gut microbiota in the activation of innate and adaptive immune cells, has gained importance. Particularly interesting is the role of the microbiota and intestinal immunity in IgAN. BAFF and APRIL can be produced by the intestinal epithelium, in response to signals triggered by TLRs once activated by the commensal bacteria present in the intestinal lumen, representing the link between microbiota and intestinal immunity. To date, even if hypothesized, this relationship in IgAN patients has not been investigated. Here, we studied the intestinal-renal axis connections analyzing levels of BAFF, April and intestinal-activated B cells in IgAN patients. Method Serum and fecal samples were collected from 44 IgAN patients, 22 non-IgA glomerulonephritides (controls) and 22 healthy subjects (HS) with similar clinical features. BAFF and APRIL serum levels were measured by ELISA assay. Metabolomic analysis of fecal microbiome was performed using Biochrom 30 series amino acid analyzer and gas-chromatography mass spectrometry/solid-phase microextraction (GC-MS/SPME) analysis. B cell subsets were investigated by FACS. Results IgAN patients had increased serum levels of BAFF cytokine compared to the control group of patients with non-IgA glomerulonephritis and compared with HS (p&lt;0.0001and p=0.012, respectively). We found that serum BAFF levels positively correlated with the levels of 24h-proteinuria in IgAN patients (r2 = 0.2269, p &lt;0.001). We correlated serum BAFF levels with fecal concentration of 5 different metabolites of 30 IgAN patients, which were previously investigated for the fecal microbiota. These organic compounds had been found at significantly higher levels in the feces of IgAN patients compared to HS. Serum BAFF levels positively correlated with the levels of fecal metabolites: 4-(1,1,3,3-tetramethylbutyl) phenol (r2 = 0.2882, p = 0.0027), p-tert-butyl-phenol (r2 = 0.386, p = 0.0003), methyl neopentyl phthalic acid (r2 = 0.3491, p =0.0007), hexadecyl ester benzoic acid (r2 = 0.2832, p =0.003) and furanone A (r2 = 0.1743, p = 0.024). Serum levels of APRIL were significantly increased in IgAN patients respect to control groups (4.49 ± 0.54 vs 2.27 ± 1 ng/ml, p=0.0014). We found a correlation between APRIL and serum creatinine (r2 = 0.159, p =0.04) and eGFR (r2 = 0.2395, p =0.0082), while no correlation was found between APRIL and fecal metabolite levels in IgAN patients. In addition, we found that subjects with IgAN have a significantly higher proportion of circulating Bregs, Memory B cells and IgA secreting-plasmablasts activated at the intestinal level (CCR9+INTB7+) compared to HS. Conclusion The results of our study showed for the first time an important correlation of serum levels of BAFF with intestinal microbiota in patients with IgAN, confirming the hypothesis of the pathogenic role of intestinal mucosal hyperresponsiveness in the IgAN patients. The intestinal-renal axis plays a crucial role in Berger's glomerulonephritis, whose complex pathogenesis may contribute several factors as genetics, pathogens and food.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Zhifang Chen ◽  
Yuejie Zhu ◽  
Rong Du ◽  
Nannan Pang ◽  
Fengbo Zhang ◽  
...  

This study is to investigate the role of regulatory B (Breg) cells in cervical cancer. In total, 70 cases of cervical cancer, 52 cases of cervical intraepithelial neoplasia (CIN), and 40 normal controls were enrolled. The percentage of Breg cells was detected by flow cytometry. Serum levels of IL-10 were measured by ELISA. The correlation between Breg cells and the clinical characterizations of cervical cancer was analyzed. The inhibition effect of Breg cells on CD8+ T cells was tested by blocking IL-10 in vitro. The percentage of CD19+CD5+CD1d+ Breg cells and the level of IL-10 of patients with cervical cancer or CIN were significantly higher than those in the control group (P<0.05). And the postoperative levels of Breg cells and IL-10 were significantly lower than the preoperative levels (P<0.05). Breg cells and the IL-10 level were positively correlated in cervical cancer patients (r=0.516). In addition, the Breg cell percentage was closely related to the FIGO stages, lymph node metastasis, tumor differentiation, HPV infection, and the tumor metastasis of cervical cancer (P<0.05). The Breg cell percentage was negatively correlated with CD8+ T cells of cervical cancer patients (r=‐0.669). The level of IL-10 in the culture supernatant of Bregs treated with CpG was significantly higher than that of non-Bregs (P<0.05). After coculture with Bregs, the quantity of CD8+ T cells to secrete perforin and Granzyme B was significantly decreased, and this effect was reversed after blocking IL-10 by a specific antibody. Breg cells are elevated in cervical cancer and associated with disease progression and metastasis. Moreover, they can inhibit the cytotoxicity of CD8+ T cells.


2019 ◽  
Vol 128 (03) ◽  
pp. 152-157
Author(s):  
Derya Demirtas ◽  
Fettah Acıbucu ◽  
Filiz Alkan Baylan ◽  
Erdinc Gulumsek ◽  
Tayyibe Saler

Abstract Background Adipokines derived from adipocytes are one of the important factors that act as circulating regulators of bone metabolism. Complement C1q/tumor necrosis factor-related protein-3 (CTRP3), a paralog of adiponectin, is are member of the CTRP superfamily. The aim of this study was to investigate the role of serum CTRP3 in the development of osteoporosis in patients with primary hyperparathyroidism. Methods This study included 53 patients with diagnosed primary hyperparathyroidism and 30 healthy controls. Laboratory tests for the diagnosis of primary hyperparathyroidism and serum levels of CTRP3 measured for all patients. Bone mineral density was obtained on lumbar spine 1 and 4 by dual energy X-ray absorptiometry. Results Serum CTRP3 levels were lower in patients with primary hyperparathyroidism than in the control group (p<0.001). In addition, primary hyperparathyroidism patients are were divided into two groups as, with and without osteoporosis; the levels of CTRP3 were lower in patients with osteoporosis than in patients without osteoporosis (p=0.004). In logistic regression analysis, only CTRP3 levels independently determined the patients to be osteoporosis (p<0.05). According to this analysis, decreased CTRP3 (per 1 ng/mL) levels were found to increase the risk of patients for osteoporosis by 6.9%. When the CTRP3 cut-off values were taken as 30 ng/mL, it determined osteoporosis with 76.4% sensitivity and 73.2% specificity. CTRP3 and urine calcium levels were independently associated with T score in dual energy X-ray absorptiometry. Conclusions CTRP3 levels were significantly decreased in patients with primary hyperparathyroidism, and it is also related to osteoporosis.


Sign in / Sign up

Export Citation Format

Share Document