Serum Cytokine Receptors in Ankylosing Spondylitis: Relationship to Inflammatory Markers and Endoplasmic Reticulum Aminopeptidase Polymorphisms

2010 ◽  
Vol 37 (9) ◽  
pp. 1907-1910 ◽  
Author(s):  
NIGIL HAROON ◽  
FLORENCE W.L. TSUI ◽  
BASIL CHIU ◽  
HING WO TSUI ◽  
ROBERT D. INMAN

Objective.Endoplasmic reticulum aminopeptidase (ERAP)1 is associated with ankylosing spondylitis (AS) and is known to be involved in the clipping of the cytokine receptors interleukin 1 receptor II (IL-1RII), IL-6Rα, and tumor necrosis factor receptor I (TNFRI). We studied the relationship of these serum cytokine receptors and their corresponding cytokines to markers of inflammation and polymorphisms in ERAP1 and ERAP2 in patients with AS.Methods.Sera from patients with AS were assayed for TNF-α, IL-1, IL-6, sTNFRI, sIL-1RII, and sIL-6Rα by ELISA. Genotyping was performed for 3 AS-associated nonsynonymous single-nucleotide polymorphisms in the ERAP1 gene [rs27044(C/G), rs10050860(C/T), and rs30187(C/T)] and 1 in the ERAP2 gene [rs2549782(T/G)]. The serum cytokine and receptor levels were compared between the different genotype groups and correlated to markers of inflammation and disease activity.Results.Eighty patients with AS (21 women) with a mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) of 5.3 ± 2.4 were enrolled. There was a significant correlation of sTNFRI with C-reactive protein (CRP; R = 0.43, p < 0.001) and erythrocyte sedimentation rate (ESR; R = 0.30, p = 0.01) but not with BASDAI. Serum cytokine levels were undetectable in the majority of patients. There was no significant difference in serum cytokines or the soluble receptors between patients with the different ERAP1/ERAP2 polymorphisms and their haplotypes. Similarly, there was no relationship of the polymorphisms with the serum cytokine levels nor the cytokine-receptor ratio.Conclusion.Soluble TNFRI levels correlate with ESR and CRP in AS. The ERAP1 and ERAP2 polymorphisms associated with AS do not influence the serum cytokine receptor levels in patients with AS.

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 414.2-415
Author(s):  
X. Huang ◽  
T. W. Li ◽  
J. Chen ◽  
Z. Huang ◽  
S. Chen ◽  
...  

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


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1629.2-1629
Author(s):  
K. Ben Abdelghani ◽  
Y. Gzam ◽  
A. Fazaa ◽  
S. Miladi ◽  
K. Ouenniche ◽  
...  

Background:Axial spondyloarthritis (ax-SpA) is a chronic rheumatic disease that mainly affects men. However, the female form of ax-SpA remains insufficiently studied.Objectives:The aim of this study was to determine the clinical characteristics, the disease activity and the functional impact of female ax-SpA in comparison with male ax-SpA.Methods:This is a retrospective study including patients diagnosed with ax-SpA fulfilling the criteria of the Assessment of SpondyloArthritis international Society (ASAS) 2009.Clinical parameters, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath ankylosing spondylitis disease activity index (BASDAI) and Bath ankylosing spondylitis functional index (BASFI) were compared between groups of female and male ax-SpA.Results:Two hundred ax-SpA patients were included with 31% of female (n=62) and a mean age of 43,3 ± 11,2 years.The mean age at onset of symptoms was 31,8 ± 8,9 years for women and 25,3 ± 9,1 years for men (p <0,0001). The mean age at diagnosis was 36,4 ± 9,6 years for women and 31,7 ± 10,4 years for men (p = 0,003). Ax-SpA with juvenile onset was noted in 1,7% of women and 12,1% of men (p = 0,02). Male ax-SpA were significantly more smokers (46.8% vs 5.4%; p <0.001). The mean duration of morning stiffness was 11,3 ± 9,2 minutes for women versus 21,6 ± 19,3 minutes for men (p = 0,005).The mean ESR was 42,4 ± 29,8 mm for women and 28,3 ± 23,4 mm for men (p = 0,001). Radiographic sacroiliitis was present in 69,3% of women versus 84,7% of men (p = 0,01). The use of anti-TNF alpha was less frequent in women (29% vs 48,5%; p = 0,01).Our study didn’t found a statistically significant difference in peripheral manifestations, extraarticular manifestations, CRP, BASDAI and BASFI between the two groups.Conclusion:Female ax-SpA seems to have a better prognosis than male with older age in disease onset, less inflammation, less radiographic sacroiliitis and less use of biological treatments.References:[1]Rusman T, et al. Curr Rheumatol Rep. 2018; 20(6).[2]Siar N, et al. Curr Rheumatol Rev. 2019;Disclosure of Interests:None declared


2002 ◽  
Vol 105 (4) ◽  
pp. 300-308 ◽  
Author(s):  
J. Kraus ◽  
B. S. Kuehne ◽  
J. Tofighi ◽  
P. Frielinghaus ◽  
E. Stolz ◽  
...  

2017 ◽  
Vol 70 (3) ◽  
pp. 278-285 ◽  
Author(s):  
Natsuko Tamura ◽  
Yasuhiro Maejima ◽  
Daisuke Tezuka ◽  
Chisato Takamura ◽  
Shunji Yoshikawa ◽  
...  

2016 ◽  
Vol 35 (9) ◽  
pp. 2235-2241 ◽  
Author(s):  
Münevver Serdaroğlu Beyazal ◽  
Turan Erdoğan ◽  
Aysegül Kücükali Türkyılmaz ◽  
Gül Devrimsel ◽  
Medine Cumhur Cüre ◽  
...  

2018 ◽  
Vol 97 (9) ◽  
pp. E18-E22 ◽  
Author(s):  
Lumy Yagueshita ◽  
Lucas Resende Lucinda ◽  
Valderilio Azevedo ◽  
Gislaine Richter Minhoto Wiemes ◽  
Nicole Richter Minhoto Wiemes ◽  
...  

Recent studies have identified sensorineural hearing loss as a possible manifestation of ankylosing spondylitis. We conducted a study of 30 patients with ankylosing spondylitis to characterize their audiologic profile and to correlate their disease activity and functional indices with their hearing thresholds. The study group was made up of 18 men and 12 women, aged 25 to 58 years (mean: 46.5), who were diagnosed with ankylosing spondylitis. We compared their findings with a socially and demographically matched group of 30 healthy controls. All 60 participants underwent an audiologic assessment, consisting of pure-tone audiometry, speech audiometry, and tympanometry. We used validated indices to assess disease activity and functional status, and we compiled information on the time of diagnosis and the types of medications used to treat the ankylosing spondylitis. We found that the average of the mean air-conduction thresholds at 0.5, 1, 2, and 4 kHz in the ankylosing spondylitis group was significantly worse than that of the controls (p = 0.004). A statistically significant difference was observed at frequencies greater than 3 kHz (p < 0.05). A subgroup of case patients who used only a tumor necrosis factor-alpha inhibitor exhibited better hearing thresholds than patients who used other drugs (p = 0.01). Differences in functional and disease activity scores between case patients with and without hearing loss were not statistically significant. We found that patients with ankylosing spondylitis did indeed have a greater prevalence of sensorineural hearing loss but that it was not correlated with either disease activity or functional status.


2012 ◽  
Vol 39 (12) ◽  
pp. 2310-2314 ◽  
Author(s):  
LAURA DURCAN ◽  
FIONA WILSON ◽  
RICHARD CONWAY ◽  
GAYE CUNNANE ◽  
FINBAR D. O’SHEA

Objective.Increased body mass index (BMI) in patients with ankylosing spondylitis (AS) is associated with a greater burden of symptoms and poor perceptions of the benefits of exercise. In AS, the effect of obesity on disease characteristics and exercise perceptions is unknown. We evaluated the prevalence of obesity in AS, to assess the attitudes of patients toward exercise and to evaluate the effect of obesity on symptoms and disease activity.Methods.Demographic data and disease characteristics were collected from 46 patients with AS. Disease activity, symptomatology, and functional disability were examined using standard AS questionnaires. BMI was calculated. Comorbidity was analyzed using the Charlson Comorbidity Index. Patients’ attitudes toward exercise were assessed using the Exercise Benefits and Barriers Scale (EBBS). We compared the disease characteristics, perceptions regarding exercise, and functional limitations in those who were overweight to those who had a normal BMI.Results.The mean BMI in the group was 27.4; 67.5% of subjects were overweight or obese. There was a statistically significant difference between those who were overweight and those with a normal BMI regarding their perceptions of exercise (EBBS 124.7 vs 136.6, respectively), functional limitation (Bath AS Functional Index 4.7 vs 2.5, Health Assessment Questionnaire 0.88 vs 0.26), and disease activity (Bath AS Disease Activity Index 4.8 vs 2.9). There was no difference between the groups in terms of their comorbid conditions or other demographic variables.Conclusion.The majority of patients in this AS cohort were overweight. They had a greater burden of symptoms, worse perceptions regarding the benefits of exercise, and enhanced awareness of their barriers to exercising. This is of particular concern in a disease where exercise plays a crucial role.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Agata Stanek ◽  
Armand Cholewka ◽  
Tomasz Wielkoszyński ◽  
Ewa Romuk ◽  
Aleksander Sieroń

Objective. The aim of the study was to estimate the impact of whole-body cryotherapy (WBC) on cardiovascular risk factors in patients with ankylosing spondylitis (AS). Material and Methods. We investigated the effect of WBC with subsequent kinesiotherapy on markers of inflammation, oxidative stress, lipid profile, and atherosclerosis plaque in male AS patients (WBC group). To assess the disease activity, the BASDAI and BASFI were also calculated. The results from the WBC group were compared with results from the kinesiotherapy (KT) group. Results. The results showed that in the WBC group, the plasma hsCRP level decreased without change to the IL-6 level. The ICAM-1 level showed a decreasing tendency. The CER concentration, as well as the BASDAI and BASFI, decreased in both groups, but the index changes of disease activity were higher in the WBC than KT patients. Additionally, in the WBC group, we observed a decrease in oxidative stress markers, changes in the activity of some antioxidant enzymes and nonenzymatic antioxidant parameters. In both groups, the total cholesterol and LDL cholesterol, triglycerides, sCD40L, PAPP-A, and PLGF levels decreased, but the parameter changes were higher in the WBC group. Conclusion. WBC appears to be a useful method of atherosclerosis prevention in AS patients.


2011 ◽  
Vol 38 (9) ◽  
pp. 1953-1956 ◽  
Author(s):  
NAI LEE LUI ◽  
ADELE CARTY ◽  
NIGIL HAROON ◽  
HUA SHEN ◽  
RICHARD J. COOK ◽  
...  

Objective.To determine the association between urolithiasis and syndesmophyte formation and the effect of urolithiasis on ankylosing spondylitis (AS) disease activity.Methods.In a longitudinal cohort of 504 patients with AS, we conducted an analysis of all patients with AS who have a history of urolithiasis. All patients met the modified New York criteria for AS. Demographics, clinical characteristics, extraarticular features, and comorbidities are systematically recorded in the database. We compared disease activity, functional indices, medical therapy and radiographic damage between AS patients with (Uro+) and without urolithiasis (Uro–) using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS).Results.Thirty-eight patients with AS (7.5%) had a history of urolithiasis in our cohort. Seventy-six patients with AS who did not have urolithiasis, matched for age, sex, and ethnicity, were selected as controls. Patients who were Uro+ were more likely to have more functional disability, based on the Bath AS Functional Index (BASFI; mean 5.3 vs 3.6 in control group, p = 0.003). Trends were noted in the Uro+ group toward higher Bath AS Disease Activity Index (BASDAI; mean 4.9 vs 4.0, p = 0.09), more peripheral joint involvement (p = 0.075), and higher frequency of biologic therapy (p = 0.09). No significant difference was detected in mSASSS or the Bath AS Metrology Index (BASMI). Significant association with diabetes mellitus (DM; p = 0.016) and Crohn’s disease (p = 0.006) was noted in the Uro+ group.Conclusion.Although there is no acceleration of syndesmophyte formation or spinal mobility restriction, more functional disability was detected in the urolithiasis group. The higher risk with concomitant DM or Crohn’s disease should alert clinicians to these comorbidities in Uro+ patients with AS.


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