scholarly journals Reactive arthritis and undifferentiated peripheral spondyloarthritis share human leucocyte antigen B27 subtypes and serum and synovial fluid cytokine profiles

Rheumatology ◽  
2020 ◽  
Author(s):  
Jyoti Ranjan Parida ◽  
Sandeep Kumar ◽  
Sakir Ahmed ◽  
Smriti Chaurasia ◽  
Ratnadeep Mukherjee ◽  
...  
Keyword(s):  
Statistical Difference ◽  
Human Leucocyte Antigen ◽  
Healthy Controls ◽  
Hla B27 ◽  
Serum Cytokine ◽  
Cytokine Profiles ◽  
Cytokine Levels ◽  
Peripheral Spondyloarthritis ◽  
Multiplex Cytokine ◽  
Age And Sex

Abstract Objectives Peripheral SpA (pSpA) is comprised of ReA, PsA, enteritis-associated arthritis and undifferentiated pSpA (upSpA). ReA and upSpA share T cell oligotypes and metabolomics in serum and SF. We investigated HLA-B27 subtypes and cytokines in serum and SF that were compared between ReA and upSpA. Methods ReA and upSpA were compared in two cohorts. In cohort I (44 ReA and 56 upSpA), HLA-B27 subtyping was carried out. In cohort II (17 ReA and 21 upSpA), serum and SF cytokines were compared using a multiplex cytokine bead assay (27 cytokines). A total of 28 healthy controls with similar age and sex to cohort II were included for comparison of serum cytokine levels. Results In cohort I, HLA-B27 was positive in 81.8% (36/44) of ReA and 85.71% (48/56) of upSpA patients. HLA-B27 typing was successful in 70 patients (30 ReA and 40 uSpA). HLA-B*2705 was the most common, followed by HLA-B*2704 and HLA-B*2707. Frequencies were the same between ReA and upSpA. In cohort II, 14 cytokines were detectable in the serum of patients. The levels of eight cytokines were higher than in the controls. The cytokine levels of ReA and upSpA were similar. Sixteen cytokines were detectable in the SF of patients. There was no statistical difference in the levels between ReA and upSpA. The cytokine profiles in sera and SF were also similar among HLA-B27-positive and negative patients. Conclusion ReA and upSpA have similar HLA-B27 subtype associations and similar cytokine profiles. They should be considered as a single entity during studies as well as clinical management.

Serum Heat Shock Protein Levels and Cytokine Profiles Are Altered In AML Patients Before Treatment and Following Disease Stabilizing Therapy,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3599-3599
Author(s):  
Hanne Fredly ◽  
Håkon Reikvam ◽  
Bjorn T. Gjertsen ◽  
Øystein Bruserud
Keyword(s):  
Valproic Acid ◽  
Heat Shock ◽  
Close Association ◽  
Serum Levels ◽  
Healthy Controls ◽  
Serum Cytokine ◽  
Cytokine Profiles ◽  
Cytokine Levels ◽  
Shock Proteins ◽  
Low Dose Cytarabine

Abstract Abstract 3599 Heat shock proteins (HSPs) maintain cellular homeostasis and function as molecular chaperones assisting protein folding and translocation. Their intracellular levels are up-regulated in response to a wide variety of insults allowing the cell to survive otherwise lethal conditions. Heat shock proteins are also released to the extracellular space and lead to a more efficient cross-presentation to specific T cells and may also initiate release of proinflammatory cytokines, stimulate NK cells and facilitate DC maturation. Extracellular Heat shock protein (HSP) 70 and HSP90 are characteristics of immunogenic apoptosis, and primary human acute myeloid leukemia (AML) cells release these mediators during spontaneous in vitro apoptosis. Primary AML cells also show constitutive release of several cytokines; these heterogeneous mediators interact through local cytokine networks that regulate growth and differentiation of normal as well as malignant hematopoietic cells. In the present study we investigated serum levels of HSP70/HSP90 and the serum cytokine profiles of patients with untreated AML and patients receiving disease-stabilizing treatment based on all-trans retinoic acid (ATRA) plus valproic acid. Serum samples from 82 untreated AML patients, including 42 patients receiving AML-stabilizing therapy, and 20 healthy controls were analysed. HSP and cytokine levels were determined by ELISA and multiplex analyses. Patients with untreated AML showed significantly increased HSP90 levels compared to healthy controls (Mann Whitney U-test, p<0.0001). The serum levels of HSP70 were significantly lower than the HSP90 levels both for the patients and for the healthy controls (p<0.0001), but the HSP70 serum levels did not differ significantly between patients and controls (Fig. 1A). HSP70 and HSP90 serum levels were significantly correlated for the AML patients (Fig. 1B, Spearman, p<0.01, R=0.425). HSP70 levels were not altered during AML-stabilizing palliative treatment, whereas HSP90 levels decreased during treatment with ATRA, valproic acid and low-dose cytarabine. High age and low differentiation of AML cells according to the FAB classification predicted lower HSP90 levels.Fig. 1Fig. 1. AML patients showed an altered serum cytokine profile compared to healthy controls with significantly altered levels of several chemokines, interleukins, growth factors and immunomodulatory cytokines (Tab.1). These cytokine levels were usually increased compared to the healthy controls. Hierarchical cluster analysis of the untreated patients showed a close association between HSP70, HSP90 and Hepatocyte growth factor (HGF) levels, these mediators also showed a significant correlation (Spearman, p<0.01). Furthermore, disease-stabilizing therapy altered the serum cytokine profile, but the profiles differed when ATRA + valproic acid was combined with either theophyllin or low-dose cytarabine. The close association between HSP70, HSP90 and HGF levels was then maintained only in the cytarabine group.Tab.1.CytokinePatientsControlsP-valueIMMUNOMODULATORY CYTOKINES    TNF-α↑8.4 (<1.5–68.5)4.5 (2.3–13.4)0.016INTERLEUKINS    IL-1α↓0.5 (<0.4–7.0)2.0 (2.0–2.9)<0.0001    IL-4↓<4.5 (<4.5–53.9)11.8 (5–17.5)<0.0001    IL-5↑<0.7 (<0.7–39.1)0.9 (<0.7–0.9)0.0001    IL-6↑5.8 (<1.1–204.6)<1.1 (<1.1–7.7)<0.0001    IL-10↑1.3 (<0.3–238.0)0.3 (<0.3–0.8)0.0005CHEMOKINES    CXCL5↓128.4 (<4.1–3252)1283.5 (341–5307)<0.0001    CXCL8/IL-8↑30.5 (<2.0–1103)10.7 (2.2–22.8)0.0003    CXCL10↑56.7 (0.5–1958)15.25 (8.5–58.4)<0.0001GROWTH FACTORS    HGF↑797.3 (1–9703)262.4 (117.3–729.3)<0.0001    GM-CSF↑0.5 (<2.0–17.2)0.9 (0.9–3.6)0.0096 We conclude that both HSP levels and serum cytokine profiles are altered in untreated AML, and the modulation of these serum levels by AML-stabilizing chemotherapy may reflect a possible mechanism for the clinical effect of this treatment strategy. The table shows serum levels for 82 AML patients and 20 healthy controls where significant differences were found (Mann-Whitney U-test, p<0.02). The results are presented as the cytokine analyzed, the alteration in the patients (↑ increased, ↓ decreased), levels in patients and healthy controls (median and range). All cytokine concentrations are presented as pg/ml, for cytokine levels not detected the values are set to < the detection limit. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Fungal Exposure and Low Levels of IL-10 in Patients with Sarcoidosis

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Marjeta Terčelj ◽  
Sanja Stopinšek ◽  
Alojz Ihan ◽  
Barbara Salobir ◽  
Saša Simčič ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Serum Levels ◽  
Healthy Controls ◽  
Serum Cytokine ◽  
Fungal Cell ◽  
Fungal Exposure ◽  
Cytokine Levels ◽  
Exposure Levels ◽  
Low Levels ◽  
Anti Inflammatory Cytokine

Background and Objectives. Sarcoidosis is an inflammatory disease with increased levels of inflammatory cytokines. Previous studies have shown a relation between the degree of granuloma infiltration and serum cytokine levels, except for interleukin- (IL-) 10. The aim of the study was to further investigate the serum levels of IL-10 in patients with sarcoidosis and relate them to fungal exposure in terms of the amount of fungi in the air of their homes andβ-glucan in bronchoalveolar lavage (BAL) fluid.Methods. Patients with sarcoidosis (n=71) and healthy controls (n=27) were enrolled. IL-10 was determined in serum. BAL was performed and the amount ofβ-glucan was measured. Domestic exposure to fungi was determined by measuring airborneβ-N-acetylhexosaminidase (NAHA) in the bedrooms.Results. At high levels of fungal exposure (domestic fungal exposure andβ-glucan in BAL), serum IL-10 values were lower than at low and intermediate exposure levels.Conclusion. The low serum IL-10 values at high fungal exposure suggest that fungal cell wall agents play a role in granuloma formation in sarcoidosis by inhibiting the secretion of the anti-inflammatory cytokine IL-10.

Clinical Manifestations but not Cytokine Profiles Differentiate Adult-onset Still’s Disease and Sepsis

2010 ◽  
Vol 37 (11) ◽  
pp. 2369-2376 ◽  
Author(s):  
MONIKA RAU ◽  
MARTIN SCHILLER ◽  
STEFAN KRIENKE ◽  
PETRA HEYDER ◽  
HANNES LORENZ ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Serum Ferritin ◽  
Elevated Serum ◽  
Clinical Manifestations ◽  
Activity Score ◽  
Adult Onset Still’S Disease ◽  
Bacterial Sepsis ◽  
Serum Cytokine ◽  
Cytokine Profiles ◽  
Cytokine Levels

Objective.To analyze clinical manifestations, serum ferritin, and serum cytokine levels in patients with adult-onset Still’s disease (AOSD) or bacterial sepsis and to evaluate their potential use for differential diagnosis.Methods.Twenty-two consecutive patients with the first flare of AOSD and 6 patients with an established diagnosis of AOSD under immunosuppressive therapy were compared with 14 patients with bacterial sepsis. Clinical manifestations were scored in a Pouchot AOSD activity score including elevated serum ferritin levels to obtain a modified Pouchot score. Serum cytokine profiles were analyzed from each patient.Results.The scores of clinical manifestations using a modified Pouchot activity score were significantly higher in patients with active untreated AOSD (mean 5.60 ± 1.93) compared with patients with chronic AOSD (mean 1.16 ± 0.98; p < 0.001) and patients with sepsis (mean 2.38 ± 1.19; p < 0.001). A modified Pouchot score ≥ 4 shows a sensitivity of 92% and a specificity of 93% for active AOSD. Serum cytokine levels of interleukin 1ß (IL-1ß), IL-6, IL-8, IL-10, IL-12, IL-18, interferon-γ, tumor necrosis factor-α, and calprotectin were elevated in acute AOSD and sepsis. Significant differences were detected only in patients with sepsis who had higher levels of IL-6 and IL-8. The overlap of the 2 groups limits the use of cytokines for differential diagnosis in individual patients.Conclusion.A modified Pouchot AOSD activity score including elevated serum ferritin levels was more useful to confirm the diagnosis of AOSD compared to patients with sepsis. Elevated serum cytokines correlate with inflammation but are of limited use to differentiate between active AOSD and bacterial sepsis.

An exploratory study demonstrating that salivary cytokine profiles are altered in children with small area thermal injury

2021 ◽  
Author(s):  
Morgan Carlton ◽  
Joanne Voisey ◽  
Lee Jones ◽  
Tony J Parker ◽  
Chamindie Punyadeera ◽  
...  
Keyword(s):  
Exploratory Study ◽  
Small Area ◽  
Burn Injury ◽  
Outpatient Setting ◽  
Blood Collection ◽  
Healthy Controls ◽  
Cytokine Concentration ◽  
Non Invasive ◽  
Cytokine Profiles ◽  
Multiplex Cytokine

Abstract Serum can be used to investigate changes in cytokine concentration following burn injury in children, however for children receiving treatment in an outpatient setting, blood is not routinely collected and therefore cannot be used for monitoring. The aim of this study was to investigate the use of saliva as a non-invasive tool for predicting burn outcomes by measuring the concentration of salivary cytokines in children with small area burns. A multiplex cytokine assay was used to measure 17 cytokines in the saliva of paediatric patients with burns (n = 20) and healthy controls (n = 20). After the removal of cytokines that had &gt;30% of samples below the assay lower detection limit, six cytokines including IL-1β, IL-4, IL-7, IL-8, MCP-1 and TNFα were analysed for association with burns. IL-1β and IL-4 were found to be significantly elevated in the paediatric burn patients compared to healthy controls. Interestingly, IL-1β was also significantly elevated in scald burns, compared to contact burns. In addition, biologically meaningful differences in cytokine concentration were identified in patients with different burn characteristics, which warrant further investigation. This exploratory study provides evidence that cytokines can be detected in the saliva of children and that salivary cytokine profiles differ between healthy controls and children with burns. Overall, this study demonstrates the value of saliva for the investigation of cytokines and its potential application in paediatric diagnostics, specifically in situations where blood collection is not appropriate.

scholarly journals Impact of Serum Cytokine Levels on EEG-Measured Arousal Regulation in Patients with Major Depressive Disorder and Healthy Controls

2016 ◽  
Vol 73 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Frank M. Schmidt ◽  
Annika Pschiebl ◽  
Christian Sander ◽  
Kenneth C. Kirkby ◽  
Julia Thormann ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Healthy Controls ◽  
Serum Cytokine ◽  
Major Depressive ◽  
Cytokine Levels

scholarly journals Is HLA-B27 Increased in Patients Diagnosed with Undifferentiated Arthritis? Results from the Leiden Early Arthritis Cohort

2014 ◽  
Vol 41 (10) ◽  
pp. 1948-1951 ◽  
Author(s):  
Floris van Gaalen ◽  
Rosaline van den Berg ◽  
Inge Verhoog ◽  
Joris Schonkeren ◽  
Annette van der Helm-van Mil ◽  
...  
Keyword(s):  
Family History ◽  
International Society ◽  
Early Arthritis ◽  
Healthy Controls ◽  
Hla B27 ◽  
Undifferentiated Arthritis ◽  
Asas Criteria ◽  
Peripheral Spondyloarthritis

Objective.Undifferentiated arthritis (UA) is a common form of arthritis. According to the Assessment of Spondyloarthritis international Society (ASAS) criteria for peripheral spondyloarthritis (pSpA), HLA-B27 can be used to help classify patients with pSpA. We tested whether HLA-B27 is increased in patients diagnosed with UA.Methods.Prevalence of HLA-B27 was compared between healthy controls and patients with UA. SpA features were compared between HLA-B27-positive and -negative UA, and SpA.Results.We found 10.1% of UA (38/375) versus 7.2% (403/5584) of controls were HLA-B27-positive (OR 1.5, 95% CI 1.0–2.1; p = 0.037). HLA-B27-positive patients with UA had more SpA features than HLA-B27-negative patients (mean 1.6, SD 1.0, and 0.9 SD 0.6; p < 0.001), but patients with SpA had significantly more SpA features (mean 4.5, SD 1.5; p < 0.001). Family history and preceding infection were features more common in HLA-B27-positive than in HLA-B27-negative UA (15.8% vs 1.3%, p = 0.04 and 15.8% vs 2.6%, p = 0.04). After HLA-B27 testing, 21 additional patients (5.6%) with UA could potentially have been classified with pSpA according to the ASAS criteria.Conclusion.HLA-B27 is more common in patients with UA than in controls. However, the yield of HLA-B27 testing in UA is low. Our results suggest that HLA-B27 testing should be reserved for patients with additional SpA features.

scholarly journals An observational study of innate immune responses in patients with acute appendicitis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Toon Peeters ◽  
Sandrina Martens ◽  
Valentino D’Onofrio ◽  
Mark H. T. Stappers ◽  
Jeroen C. H. van der Hilst ◽  
...  
Keyword(s):  
Acute Appendicitis ◽  
Immune Responses ◽  
Complicated Appendicitis ◽  
Healthy Controls ◽  
Innate Immune Responses ◽  
Serum Cytokine ◽  
Post Surgery ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Recognition Receptor

Abstract Acute appendicitis is a common surgical emergency worldwide. Exaggerated immune responses could be associated with appendicitis. This study aimed at characterizing immune responses towards a large variety of gut commensals and pathogens, and pattern recognition receptor (PRR) ligands, and investigating the course of systemic inflammation in a prospective cohort of acute appendicitis patients. PBMC responses of 23 patients of the cohort and 23 healthy controls were characterized more than 8 months post-surgery. Serum cytokine levels were measured in 23 patients at the time of appendicitis and after one month. CRP, WBC and percentage of neutrophils were analyzed in the total cohort of 325 patients. No differences in PBMC responses were found between patients and controls. Stronger IL-10 responses were found following complicated appendicitis. A trend towards lower IL-8 responses was shown following gangrenous appendicitis. Serum IL-10 and IL-6 were significantly elevated at presentation, and IL-6, IL-8 and TNF-α levels were higher in complicated appendicitis. Routine biomarkers could predict severity of appendicitis with high specificities, but low sensitivities. Cytokine responses in patients following acute appendicitis did not differ from healthy controls. Higher serum cytokine levels were found in acute complicated and gangrenous cases. Further research into discriminative biomarkers is warranted.

A high density SNP genotyping approach within the 19q13 chromosome region identifies an association of a CNOT3 polymorphism with ankylosing spondylitis

2012 ◽  
Vol 71 (5) ◽  
pp. 714-717 ◽  
Author(s):  
Roberto Díaz-Peña ◽  
Ana M Aransay ◽  
Beatriz Suárez-Álvarez ◽  
Jacome Bruges-Armas ◽  
Naiara Rodríguez-Ezpeleta ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
High Throughput ◽  
Human Leucocyte Antigen ◽  
Chromosome Region ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Hla B27 ◽  
Single Nucleotide ◽  
Sliding Windows ◽  
Genomic Variants

ObjectiveTo identify genomic variants in the 19q13 chromosome region associated with ankylosing spondylitis (AS) in human leucocyte antigen (HLA)-B27-positive populations.MethodsHigh-throughput genotyping of 1536 haplotype-tag single nucleotide polymorphisms (SNPs) was performed in 249 patients with AS and 302 healthy controls. Some of the identified associations were validated by genotyping four SNPs in two additional cohorts consisting of 412 cases/301 controls and 144 cases/203 controls. All individuals selected (both cases and controls) were HLA-B27-positive.ResultsTwo markers in two different genes (CNOT3 and LAIR2) showed significant association (p<10−3) with AS. In addition, sliding windows analysis showed association of groups of adjacent SNPs in regions located around CNOT3 (Chr19: 59347459-59356564, p=2.43×10−4 to 6.54×10−4). The associations were validated by genotyping four SNPs from regions located near LAIR2 and CNOT3 genes (rs1055234, rs8111398, rs2287828 and rs4591276) in two additional cohorts. The CNOT3 polymorphism (rs1055234) remained associated with AS (combined p=9.73×10−6). One SNP, located downstream of KIR3DL1, was detected which, tested in combination with HLA-Bw4I80, was associated with AS.ConclusionA novel significant association was detected between SNP rs1055234 and AS susceptibility.

scholarly journals Saliva and Serum Cytokine Profiles During Oral Ulceration in Behçet’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Tanya Novak ◽  
Mojgan Hamedi ◽  
Lesley Ann Bergmeier ◽  
Farida Fortune ◽  
Eleni Hagi-Pavli
Keyword(s):  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Serum Cytokine ◽  
Oral Ulceration ◽  
Behcet's Disease ◽  
Cytokine Profiles ◽  
Oral Ulcers ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Ifn Γ

Behçet’s disease (BD) is a chronic, multi-systemic disorder of unknown aetiology typified by recurrent oral and genital mucocutaneous lesions, uveitis and vasculitis. Innate and adaptive immune system dysregulation has been implicated in pathogenesis with alterations in serum cytokine profiles. Few studies have investigated salivary cytokines in BD, despite more than 90% of BD patients first presenting with oral ulceration. The aim of this pilot study was twofold; firstly to investigate whether cytokine levels in matched serum and saliva samples show a differential profile in BD (with and without oral ulcers), recurrent aphthous stomatitis (RAS) and healthy controls (HCs), and secondly, to explore if any differential profiles in serum and/or saliva could provide a panel of cytokines with diagnostic and therapeutic potential for BD. Concentrations of 12 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-γ, TNF-α, TNF-β) were measured using the Human Th1/Th2 11-Plex FlowCytomix™ kit with IL-17A, in BD (N=20), RAS (N=6) and HCs (N=10). A differential range of cytokines was detected in serum and saliva with the majority of cytokine levels higher in saliva. The most prevalent salivary cytokines were IL-1β, IL-2, IL-8, IL-10 and TNF-α present in all samples in contrast to serum where the most prevalent cytokine detected was IL-8 (91.9%). The least abundant cytokine was IFN-γ in both saliva (43.2%) and serum (2.7%). After normalizing saliva for protein content, BD patients with oral ulcers (BD-MA) had significantly higher levels of salivary IL-1β (p=0.01), IL-8 (p=0.02), TNF-α (p=0.004) and IL-6 (p=0.01) than HCs. Notably, BD patients without oral ulcers (BD-MQ) also had significantly higher salivary IL-1β, IL-8 and TNF-α (p ≤ 0.05) than HCs. During relapsed (BD-RE) and quiet (BD-Q) systemic episodes, salivary IL-β and TNF-α were also significantly increased with IL-8 significantly higher only in BD-Q (p=0.02). BD oral ulcers signify a potential reactivation of systemic inflammation. Identifying cytokines released during asymptomatic episodes and oral ulceration might lead to targeted drug therapy to prevent recurrent oral ulcers and possible disease relapse. This is the first study to report salivary cytokine levels in BD. The detectable levels suggests cytokine profiling of BD saliva may provide an alternative, less invasive, sensitive procedure for frequent monitoring of disease activity and progression.

scholarly journals Do the Th17 Cells Play a Role in the Pathogenesis of Leptospirosis?

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Kanchana Bandara ◽  
Chinthika Gunasekara ◽  
Manjula Weerasekera ◽  
Chamil Marasinghe ◽  
Nilantha Ranasinghe ◽  
...  
Keyword(s):  
Renal Failure ◽  
Th17 Cells ◽  
Liver Involvement ◽  
Control Group ◽  
Healthy Controls ◽  
Serum Cytokine ◽  
Significant Elevation ◽  
Elisa Kit ◽  
Cytokine Levels ◽  
Healthy Control

Objectives. The aim of this study was to determine the level of five different pro- and anti-inflammatory cytokines to study the inflammatory response of leptospirosis. Materials and methods. The serum cytokine levels of IL-10, IL-17A, IL-21, IL-23, and TNF-α were investigated in 57 patients with leptospirosis and 12 healthy controls using a commercially available ELISA kit (Mabtech, Sweden). Statistical analysis was done using Graphpad Prism. Results. Elevation of serum IL-10 and IL-17A levels and significant elevation of serum IL-21 (p=0.002), IL-23 (p=0.002), and TNF-α (p=0.039) were observed among leptospirosis patients compared to the healthy control group. The two major complications observed among these patients were renal failure and liver involvement. Renal failure was significantly associated with elevation of IL-21 and IL-23, while patients with liver involvement had a significant elevation of IL-21, IL-23, and TNF-α. Conclusion. Elevation of IL-17A together with the significant elevation of IL-21 and IL-23 suggests a possible involvement of Th17 cells in the immunopathogenesis of leptospirosis.

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