Metabolic Disorders/Obesity Is a Primary Risk Factor in Hidradenitis Suppurativa: An Immunohistochemical Real-World Approach

Dermatology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Katarzyna P. Kaleta ◽  
Georgios Nikolakis ◽  
Amir M. Hossini ◽  
Ottfried Balthasar ◽  
Daifallah Almansouri ◽  
...  
Keyword(s):  
Differential Expression ◽  
Hidradenitis Suppurativa ◽  
Metabolic Disorders ◽  
Environmental Toxins ◽  
Protein Markers ◽  
Lesional Skin ◽  
Markers Of Inflammation ◽  
Significant Difference ◽  
Strong Immunoreactivity ◽  
Primary Risk Factor

<b><i>Background:</i></b> Hidradenitis suppurativa (HS) is an inflammatory, potentially scarring disease of the hair follicle, affecting the apocrine gland-bearing skin areas. The major comorbid disorders associated with the occurrence or the aggravation of the disease are obesity and smoking. Numerous efforts to dissociate these factors led to controversial results. <b><i>Objectives:</i></b> To assess the importance of metabolic disorders/obesity, smoking/environmental toxins, and inflammation in HS by utilizing the differential expression of major relevant protein markers in lesional skin of obese/smoking versus non-obese/non-smoking HS patients. <b><i>Methods:</i></b> Lesional skin specimens deriving from two groups of HS patients (BMI &#x3e;30 and smokers, <i>n</i> = 12 vs. BMI &#x3c;30 and non-smokers, <i>n</i> = 10) were stained with antibodies raised against irisin, PPARγ, and IGF-1R, which correlate with metabolic disorders/obesity, EGFR and AhR, associated with smoking, and IL-17, IL-17R, and S100A8, as markers of inflammation. <b><i>Results:</i></b> Metabolic disorders/obesity-related markers exhibited marked differential expression between the two groups, while smoking-associated markers a limited one. IL-17R expression was stronger in obese/smokers, and S100A8 staining exhibited intense strong immunoreactivity in both groups without significant difference. <b><i>Conclusions:</i></b> The notion that obesity plays a role in HS development appears to be supported by the prominent regulation of the associated lesional biomarkers. Tobacco smoking might contribute less to HS than previously suspected.

scholarly journals POS0369 ELEVATED EXPRESSION OF TIM-3 ON NEUTROPHILS CORRELATES WITH DISEASE ACTIVITY AND SEVERITY OF ANKYLOSING SPONDYLITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 414.2-415
Author(s):  
X. Huang ◽  
T. W. Li ◽  
J. Chen ◽  
Z. Huang ◽  
S. Chen ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Immune Cells ◽  
Clinical Manifestations ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Bacterial Killing ◽  
Markers Of Inflammation ◽  
Significant Difference

Background:Ankylosing spondylitis (AS) is a type of common, chronic inflammatory disease that compromises the axial skeleton and sacroiliac joints, causing inflammatory low back pain and progressive spinal stiffness, over time some patients develop spinal immobility and ankylosis which can lead to a decrease in quality of life. The last few decades, evidence has clearly indicated that neutrophil also plays key roles in the progression of AS. However, the immunomodulatory roles and mechanisms of neutrophils in AS are poorly understood. T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) has been reported as an important regulatory molecule, expressed and regulated on different innate immune cells, plays a pivotal role in several autoimmunity diseases. Recent study indicates that Tim3 is also expressed on neutrophils. However, the frequency and roles of Tim3-expressing neutrophils in AS was not clear.Objectives:In this study, we investigated the expression of Tim3 on neutrophils in AS patients and explored the correlation between the level of Tim3-expressing neutrophils and the disease activity and severity of AS.Methods:Patients with AS were recruited from Guangdong Second Provincial General Hospital (n=62). Age/sex-matched volunteers as Healthy controls (HC) (n=39). The medical history, clinical manifestations, physical examination, laboratory measurements were recorded. The expression of costimulatory molecules including programmed death 1 (PD-1), Tim-3 on neutrophils were determined by flow cytometry. The mRNA expression of PD-1 and Tim-3 was determined by real-time PCR. The levels of Tim3-expressing neutrophils in AS patients were further analyzed for their correlation with the markers of inflammation such as ESR,CRP,WBC and neutrophil count(NE), as well as disease activity and severity of AS. The expression of Tim3 on neutrophils was monitored during the course of treatment (4 weeks).Results:The expression of Tim3 on neutrophils in patients with AS was increased compared to the HC (Figure 1A). However, significant difference was observed in the frequency of PD-1-expressing neutrophils between AS patients and HC (Figure 1B). The expression analysis of Tim-3 mRNA, but not PD-1, confirmed the results obtained from flow cytometry (Figure 1C). The level of Tim3-expressing neutrophils in patients with AS showed an positive correlation with ESR, CRP and ASAS-endorsed disease activity score (ASDAS) (Figure 1D). Moreover, the frequency of Tim3-expressing neutrophils in active patients(ASDAS≥1.3) was increased as compare with the inactive patients (ASDAS<1.3) (Figure 1E). As shown in Figure 1F, the frequency of Tim3-expressing neutrophils decreased after the treatment.Conclusion:Increased Tim-3 expression on neutrophils may be a novel indicator to assess disease activity and severity in AS, which may serves as a negative feedback mechanism preventing potential tissue damage caused by excessive inflammatory responses in AS patients.References:[1]Han, G., Chen, G., Shen, B. & Li, Y., Tim-3: an activation marker and activation limiter of innate immune cells. FRONT IMMUNOL 4 449 (2013).[2]Vega-Carrascal, I. et al., Galectin-9 signaling through TIM-3 is involved in neutrophil-mediated Gram-negative bacterial killing: an effect abrogated within the cystic fibrosis lung. J IMMUNOL 192 2418 (2014).Figure 1.(A,B)The expression of Tim3 and PD-1 on neutrophils in AS and HC were determined by flow cytometry.(C) The expression of Tim3 and PD-1 on neutrophils in AS and HC were determined by RT-PCR.(D)The correction between Tim3-expressing neutrophils and ESR,CRP,ASDAS.(E) The expression of Tim3 on neutrophils in active and inactive patients.(F) Influence of treatment on the frequency of Tim3-expressing neutrophils.Disclosure of Interests:None declared

3D-SeboSkin Model for Human ex vivo Studies of Hidradenitis Suppurativa/Acne Inversa

Dermatology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Xiaoxiao Hou ◽  
Amir M. Hossini ◽  
Georgios Nikolakis ◽  
Ottfried Balthasar ◽  
Andreas Kurtz ◽  
...  
Keyword(s):  
Differential Expression ◽  
Hidradenitis Suppurativa ◽  
Structural Integrity ◽  
Ex Vivo ◽  
Human Model ◽  
Acne Inversa ◽  
Inflammatory Skin Disease ◽  
Preclinical Research ◽  
Dermal Tissue ◽  
Uninvolved Skin

<b><i>Background:</i></b> Hidradenitis suppurativa/acne inversa (HS) is a chronic, recurrent inflammatory skin disease. Its pivotal pathogenetic event is believed to be the occlusion of the hair follicle generating a perifollicular lympho-histiocytic inflammation. However, knowledge of the exact HS pathogenesis requires further research. <b><i>Objective:</i></b> To develop a human HS model applicable in preclinical research which could help to understand the pathophysiology of HS and to determine the action of therapeutic candidates. <b><i>Methods:</i></b> The 3D-SeboSkin technology was applied to maintain explants of involved and uninvolved skin of HS patients ex vivo for 3 days. Detection of differential expression of previously detected HS biomarkers was performed by immunohistochemistry in a group of female patients (<i>n</i> = 9, mean age 37.2 ± 8.4 years). <b><i>Results:</i></b> The application of the 3D-SeboSkin model preserved the structural integrity of lesional and perilesional HS skin ex vivo, as previously described for healthy skin. Moreover, the HS 3D-SeboSkin setting maintained the differential expression and pattern of several HS biomarkers (S100A9, KRT16, SERPINB3) in epidermal and dermal tissue and the appendages. <b><i>Conclusion:</i></b> We have validated HS 3D-SeboSkin as a reproducible, human model, which is appropriate for preclinical lesional and perilesional HS skin studies ex vivo.

scholarly journals MCPIP1/Regnase-1 Expression in Keratinocytes of Patients with Hidradenitis Suppurativa: Preliminary Results

2021 ◽  
Vol 22 (14) ◽  
pp. 7241
Author(s):  
Piotr K. Krajewski ◽  
Weronika Szukała ◽  
Agata Lichawska-Cieślar ◽  
Łukasz Matusiak ◽  
Jolanta Jura ◽  
...  
Keyword(s):  
Western Blot ◽  
Mrna Expression ◽  
Hidradenitis Suppurativa ◽  
Skin Lesions ◽  
Healthy Controls ◽  
Lesional Skin ◽  
Chemotactic Protein ◽  
Healthy Control ◽  
Mrna And Protein Expression ◽  
Skin Biopsies

The pathogenesis of hidradenitis suppurativa (HS) is yet to be fully understood. However, inflammation is a key element in the development of skin lesions. The aim of this study was to evaluate the expression of monocyte chemotactic protein-1-induced protein-1 (MCPIP1) in the skin of patients suffering from HS. Skin biopsies of 15 patients with HS and 15 healthy controls were obtained and processed for immunohistochemistry, western blot, and real time PCR. The highest mean MCPIP1 mRNA expression was found in the inflammatory lesional skin of HS patients. It was significantly higher than MCPIP1 mRNA expression in the biopsies from both healthy controls and non-lesional skin of HS patients. Western blot analysis indicated that expression of MCPIP1 was elevated within both lesional and non-lesional skin compared to the healthy control. The increased MCPIP1 mRNA and protein expression level in HS lesions may indicate its possible role in the disease pathogenesis.

Differences in triglyceride levels before and after whey protein intervention in field workers exposed and unexposed to arsenic

2021 ◽  
Vol 9 (2) ◽  
pp. 166-171
Author(s):  
Eka Putri Rahmadhani ◽  
Ani Margawati ◽  
Apoina Kartini
Keyword(s):  
Whey Protein ◽  
Dairy Products ◽  
Metabolic Disorders ◽  
Fat Metabolism ◽  
Exposed Group ◽  
The Body ◽  
Unexposed Group ◽  
Significant Difference ◽  
Before And After ◽  
Field Workers

Background: A work environment that is exposed to heavy metals, such as a coal mining environment, can change fat metabolism in the body. Changes in fat metabolism will lead to cardiovascular disease. Consumption of dairy products, e.g. whey protein, can reduce the risk of metabolic disorders and cardiovascular disease.Objectives: To test and analyze the differences in triglyceride levels before and after whey protein intervention to field workers with different working conditions.Materials and Methods: This experimental research with pretest and posttest was conducted on field workers at PT Bukit Asam Tbk. Tarahan Port Unit, Lampung as an Arsenic exposed group and PTPN VII Way Berulu Business Unit as an Arsenic unexposed group. Both groups received 24 grams of whey protein daily for 28 days. The triglyceride levels before and after the intervention were measured by laboratory analysis using the enzymatic calorimetry method. The data were analyzed using independent t-test, Mann Whitney test, and Wilcoxon test.Results: The average triglyceride levels increased by 50.48 ± 98.09 mg/dL in the exposed group and 16.78 ± 67.67 mg/dL in the unexposed group. There was a significant difference in triglyceride levels before and after the whey protein intervention in the two groups.Conclusions: The whey protein intervention increased the triglyceride level in the exposed group and decreased it in the unexposed group.

MO477SERUM C-REACTIVE PROTEIN AND PROCALCITONIN LEVELS IN HEMODIALYSIS AND INTRADIALYTIC ALTERATIONS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Makrouhi Sonikian ◽  
Aggeliki Barbatsi ◽  
Eugenia Karakou ◽  
Theodoros Chiras ◽  
Jacob Skarakis ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Control Group ◽  
Healthy Controls ◽  
C Reactive Protein ◽  
Polysulfone Membrane ◽  
Reactive Protein ◽  
Markers Of Inflammation ◽  
Dialysate Flow Rate ◽  
Significant Difference ◽  
Serum Crp

Abstract Introduction C-reactive protein (CRP) and procalcitonin (PCT) are widely used as markers of inflammation and infection in general population and in chronic hemodialysis (HD) as well. However, in dialysis (D) patients, serum CRP and PCT levels may be elevated even in the absence of inflammatory or infectious disease and diagnostic process is a challenge in such cases. We studied HD patients' laboratory profile concerning CRP and PCT. Subjects and Methods We studied 25 stable HD patients, M/F=22/3, aged 68(44-89) years, dialyzed thrice weekly for 55(6-274) months with a dialysate flow rate of 700 ml/min, with a residual daily diuresis less than 200 ml, Kt/V values of 1,44±0,3 and no signs of infection. Patients were classified in two groups. Group A included 10 patients on pre-dilution online hemodiafiltration (HDF). Group B consisted of 15 patients on conventional HD with low-flux polysulfone membrane. Twenty healthy subjects formed a control group C. Serum CRP and PCT levels were measured in duplicate in A and B groups before and at the end of mid-week dialysis sessions and also in C group. Results Pre-D serum CRP values in the total of patients were higher than those in healthy controls (10,89±19,29 vs 2,54±1,28 mg/L-p=0,004). Compared with group C, pre-D CRP values were higher only in B group (15,98±24,54 mg/L-p=0,001) but not in A group (4,09±3,33 mg/L-p=NS). There was a significant difference in pre-D serum CRP values between A and B groups (p=0,028). At the end of D session serum CRP values showed a tendency to increase in both groups A (5,16±4,81 mg/L) and B (17,00±27,00 mg/L) but differences were not significant. Pre-D serum PCT values in the total of patients were higher than those in healthy controls (0,82±0,9 vs 0,29±0,55 ng/ml-p&lt;0,001). Compared with group C, pre-D PCT values were higher in both A group (0,52±0,15 ng/ml-p&lt;0,001) and B group (1,01±1,13 ng/ml-p=0,006). There was no significant difference in pre-D serum PCT values between A and B groups (p=0,261). At the end of D session serum PCT values decreased in A group (0,32±0,11 ng/ml-p&lt;0,001) and increased in B group (1,12±1,21 ng/ml-p=0,014). Conclusions In patients on both conventional low-flux HD and online HDF pre-D serum CRP and PCT levels were higher than those in healthy subjects. Dialysis modality and membrane flux did not affect post-D serum CRP values, but post-PCT values decreased in online HDF. PCT usefulness might be limited in dialysis with high-flux membranes. Cut-off values have to be established for both markers to eliminate confusion in diagnosis of inflammatory and infectious diseases in hemodialyzed patients.

scholarly journals Assessment of the hemogram parameters in patients with paroxysmal supraventricular tachycardia: a retrospective study

2020 ◽  
Vol 66 (10) ◽  
pp. 1371-1375
Author(s):  
Mehmet Cosgun ◽  
Yilmaz Gunes ◽  
Isa Sincer ◽  
Asli Kurtar Mansiroglu
Keyword(s):  
Retrospective Study ◽  
Supraventricular Tachycardia ◽  
University Hospital ◽  
Control Group ◽  
Paroxysmal Supraventricular Tachycardia ◽  
Monocyte Count ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Markers Of Inflammation ◽  
Significant Difference

SUMMARY OBJECTIVE: Inflammation has been suggested as a potential mechanism in the pathogenesis of arrhythmia. Hemogram parameters such as monocyte count to high-density lipoprotein cholesterol ratio (MHR), neutrophil/lymphocyte ratio (NLR), and monocyte/lymphocyte ratio (MLR) have been considered to be markers of inflammation and new cardiovascular risk predictors. This retrospective study aimed to investigate the relationship between MHR, NLR, and MLR in patients with paroxysmal supraventricular tachycardia (PSVT). METHODS: A retrospective study conducted at a university hospital in Bolu, Turkey, between 2017 and 2019. Our study included 196 patients who underwent electrophysiological study (EPS) due to palpitation or documented PSVT on electrocardiography (ECG). Patients having documented atrioventricular nodal re-entrant tachycardia (AVNRT) on ECG or inducible AVNRT on EPS were included in the PSVT group (n=130), and patients with palpitation but without inducible arrhythmia on EPS (n=66) were included in the control group. Routine biochemical and hemogram tests were performed before the EPS procedure. RESULTS: When hemogram parameters were compared, there was no statistically significant difference in MHR values [0.010 (0.001-0.030) vs 0.010 (0.001-0.020) p =0.67]. Additionally, both NLR [2.21(0.74-11.36) vs 1.98(0.72-24.87) p=0.13] and MLR [0.25 (0.03-1.05) vs 0.24(0.07-1.39) p=0.41] were not statistically significant between the two groups. CONCLUSION: There is no significant difference in PSVT patients regarding hemogram parameters including white blood cell subtypes, MLR, NLR, and MHR. Therefore the evaluation of hemogram parameters may not be clinically relevant for PSVT patients.

26528 Hidradenitis suppurativa disease severity associated with objective markers of inflammation and patient-reported pain

2021 ◽  
Vol 85 (3) ◽  
pp. AB20
Author(s):  
Tyler M. Andriano ◽  
Kristen P. Pacific ◽  
Kayla M. Babbush ◽  
Gabrielle Benesh ◽  
H. Dean Hosgood ◽  
...  
Keyword(s):  
Disease Severity ◽  
Hidradenitis Suppurativa ◽  
Markers Of Inflammation ◽  
Patient Reported

Association between circulating inflammatory markers and marksmanship following intense military training

2018 ◽  
Vol 165 (6) ◽  
pp. 391-394
Author(s):  
Yftach Gepner ◽  
J R Hoffman ◽  
M W Hoffman ◽  
H Zelicha ◽  
H Cohen ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Test Performance ◽  
Military Training ◽  
Protein Markers ◽  
Military Operations ◽  
Field Training ◽  
Markers Of Inflammation ◽  
Tnf Α ◽  
Combat Unit ◽  
Factor Α

IntroductionIntense military operations during deployment or training are associated with elevations in inflammatory cytokine markers. However, the influence of an inflammatory response on military-specific skills is unclear. This study examined the association between brain-derived neurotrophic factor (BDNF), glial fibrillar acidic protein, markers of inflammation, marksmanship and cognitive function following a week of intense military field training.MethodsTwenty male soldiers (20.1±0.6 years; 1.78±0.05m; 74.1±7.9kg) from the same elite combat unit of the Israel Defense Forces volunteered to participate in this study. Soldiers completed a five-day period of intense field training including navigation of 27.8km/day with load carriages of ~50% of their body mass. Soldiers slept approximately fivehours per day and were provided with military field rations. Following the final navigational exercise, soldiers returned to their base and provided a blood sample. In addition, cognitive function assessment and both dynamic and static shooting (15 shots each) were performed following a 200 m gauntlet, in which soldiers had to use hand-to-hand combat skills to reach the shooting range.ResultsResults revealed that tumour necrosis factor-α (TNF-α) concentrations were inversely correlated with dynamic shooting (r=−0.646, p=0.005). In addition, a trend (r=0.415, p=0.098) was noted between TNF-α concentrations and target engagement speed (ie, time to complete the shooting protocol). BDNF concentrations were significantly correlated with the Serial Sevens Test performance (r=0.672, p=0.012).ConclusionThe results of this investigation indicate that elevated TNF-α concentrations and lower BDNF concentrations in soldiers following intense military training were associated with decreases in marksmanship and cognitive function, respectively.

Procalcitonin and Conventional Markers of Inflammation in Peritoneal Dialysis Patients and Peritonitis

2006 ◽  
Vol 26 (2) ◽  
pp. 240-248 ◽  
Author(s):  
Galip Guz ◽  
Bulent Colak ◽  
Kenan Hizel ◽  
Kadriye A. Reis ◽  
Yasemin Erten ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Hemodialysis Patients ◽  
Biochemical Tests ◽  
Reactive Protein ◽  
Markers Of Inflammation ◽  
Median Serum ◽  
Significant Difference

Objectives To determine the significance of a newly described marker of inflammation procalcitonin (PCT), and to investigate its relationship to conventional markers of inflammation, such as C-reactive protein (CRP), fibrinogen, and erythrocyte sedimentation rate (ESR), in patients on peritoneal dialysis (PD) and with peritonitis. Design A prospective, observational clinical study. Setting The Nephrology Division of a University-affiliated teaching hospital. Patients and Methods 51 consecutive patients on PD were included in the study. Of this number, 16 developed peritonitis during the observational period. Baseline PCT, CRP, and fibrinogen concentrations and ESR of 51 PD patients were determined at a time point (TB) prior to any evidence of infection. These results were compared with laboratory values from 74 hemodialysis patients and 34 nonuremic control subjects. All PD patients then were followed prospectively for evidence of peritonitis. In addition to routine blood tests, including hemoglobin and leukocyte count, and routine biochemical tests, blood samples were taken to measure PCT, CRP, and fibrinogen concentrations and ESR at the time (T0) when patients first were diagnosed with PD peritonitis and also on the 4th (T4) and the 14th (T14) days after treatment for peritonitis was initiated. PCT was assayed by immunoluminometry. Results No significant difference was observed between baseline median serum PCT concentrations in PD and hemodialysis patients; however, in both groups, baseline median PCT concentrations were significantly higher than those of nonuremic controls ( p < 0.05). The 16 patients on PD who developed peritonitis had 21 PD peritonitis episodes during the study period. The increased PCT concentration observed at T0 in PD peritonitis episodes decreased with therapy, and this change was statistically significant ( p < 0.05). In a receiver operating characteristic curve analysis for peritonitis, the area under the curve (AUC) for PCT was 0.80, which was significantly lower than the AUC for CRP and greater than the AUCs for fibrinogen and ESR. The sensitivity of PCT for peritonitis was lower than the sensitivity of conventional markers of inflammation; however, the specificity of PCT was higher. Conclusions Median serum PCT concentration in PD patients was significantly higher than in nonuremic controls but not hemodialysis patients. Serum PCT concentrations may serve as a useful adjunct to traditional markers of inflammation in detecting and monitoring inflammation and peritonitis in PD patients.

scholarly journals Surgical fat removal exacerbates metabolic disorders but not atherogenesis in LDLR−/− mice fed on high-fat diet

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lin Liu ◽  
Chenxi Liang ◽  
Xiaowei Wang ◽  
Xiayu Ding ◽  
Yingjing Lu ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Metabolic Disorders ◽  
Subcutaneous Fat ◽  
Surgical Removal ◽  
High Fat ◽  
Fat Depots ◽  
Systemic Insulin Resistance ◽  
Significant Difference ◽  
Fat Removal ◽  
Adipose Dysfunction

AbstractLipodystrophy is a severe adipose dysfunction that can be classified as congenital or acquired lipodystrophy, in term of the etiology. Previous knowledge about the metabolic disorders and cardiovascular consequences were mostly obtained from lipodystrophic mice with genetic defects. To completely rule out the genetic influence, we established a mouse model of acquired generalized lipodystrophy by surgical removal of multiple fat depots, including subcutaneous fat in the inguinal, visceral fat in the epididymis and brown fat in the scapula, in atherosclerosis-prone LDLR−/− mice which were fed with a high-fat diet (HFD). It was observed that fat removal increased diet-induced hyperlipidemia, especially hypercholesteremia, as early as 2 weeks after HFD and till the end of HFD feeding. After 12 weeks on the HFD, the residual fats of fat-removed mice were found expanded. Although fat removal aggravated diet-induced lipid deposition in the liver and systemic insulin resistance, there was no significant difference in atherogenesis in fat-removed mice compared with sham-operated control mice. Acquired generalized lipodystrophy by surgical fat removal promoted metabolic disorders but not atherogenesis in LDLR−/− mice fed on HFD.

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