Female Ankylosing Spondylitis Patients Research Articles

Identification of sex-specific biomarkers related to programmed cell death and analysis of immune cells in ankylosing spondylitis

Ankylosing spondylitis (AS) stands as a persistent inflammatory ailment predominantly impacting the axial skeleton, with the immune system and inflammation intricately entwined in its pathogenesis. This study endeavors to elucidate gender-specific patterns in immune cell infiltration and diverse forms of cell demise within the AS milieu. The aim is to refine the diagnosis and treatment of gender-specific AS patients, thereby advancing patient outcomes. In the pursuit of our investigation, two datasets (GSE25101 and GSE73754) pertinent to ankylosing spondylitis (AS) were meticulously collected and normalized from the GEO database. Employing the CIBERSORT algorithm, we conducted a comprehensive analysis of immune cell infiltration across distinct demographic groups and genders. Subsequently, we discerned differentially expressed genes (DEGs) associated with various cell death modalities in AS patients and their healthy counterparts. Our focus extended specifically to ferroptosis-related DEGs (FRDEGs), cuproptosis-related DEGs (CRDEGs), anoikis-related DEGs (ARDEGs), autophagy-related DEGs (AURDEGs), and pyroptosis-related DEGs (PRDEGs). Further scrutiny involved discerning disparities in these DEGs between AS patients and healthy controls, as well as disparities between male and female patients. Leveraging machine learning (ML) methodologies, we formulated disease prediction models employing cell death-related DEGs (CDRDEGs) and identified biomarkers intertwined with cell death in AS. Relative to healthy controls, a myriad of differentially expressed genes (DEGs) linked to cell death surfaced in AS patients. Among AS patients, 82 FRDEGs, 29 CRDEGs, 54 AURDEGs, 21 ARDEGs, and 74 PRDEGs were identified. In male AS patients, these numbers were 78, 33, 55, 24, and 94, respectively. Female AS patients exhibited 66, 41, 40, 17, and 82 DEGs in the corresponding categories. Additionally, 36 FRDEGs, 14 CRDEGs, 19 AURDEGs, 10 ARDEGs, and 36 PRDEGs exhibited differential expression between male and female AS patients. Employing machine learning techniques, LASSO, RF, and SVM-RFE were employed to discern key DEGs related to cell death (CDRDDEGs). The six pivotal CDRDDEGs in AS patients, healthy controls, were identified as CLIC4, BIRC2, MATK, PKN2, SLC25A5, and EDEM1. For male AS patients, the three crucial CDRDDEGs were EDEM1, MAP3K11, and TRIM21, whereas for female AS patients, COX7B, PEX2, and RHEB took precedence. Furthermore, the trio of DDX3X, CAPNS1, and TMSB4Y emerged as the key CDRDDEGs distinguishing between male and female AS patients. In the realm of immune correlation, the immune infiltration abundance in female patients mirrored that of healthy controls. Notably, key genes exhibited a positive correlation with T-cell CD4 memory activation when comparing male and female patient samples. This study engenders a more profound comprehension of the molecular underpinnings governing immune cell infiltration and cell death in ankylosing spondylitis (AS). Furthermore, the discernment of gender-specific disparities among AS patients underscores the clinical significance of these findings. By identifying DEGs associated with diverse cell death modalities, this study proffers invaluable insights into potential clinical targets for AS patients, taking cognizance of gender-specific nuances. The identification of gender-specific biological targets lays the groundwork for the development of tailored diagnostic and therapeutic strategies, heralding a pivotal step toward personalized care for AS patients.

IL-17-producing cells in ankylosing spondylitis patients show gender-based differences in gene expression.

Gender has been shown to impact disease expression in ankylosing spondylitis (AS) and Th17 cells play a key role in AS pathogenesis. To better understand what Th17-associated immune pathways are different between men and women, we compared the transcriptome of IL-17-enriched peripheral blood mononuclear cells (PBMCs) in male and female AS patients, with a particular focus on inflammatory cytokine genes. PBMCs were collected from 10 female and 11 male AS patients at the Clinical Research Unit of MetroHealth Medical Center. IL-17-enriched PBMCs were isolated and stimulated with CytoStim. RNA-sequencing (RNA-seq) was performed on the samples, and the data were analysed using iPathwayGuide. Inflammatory markers and genes related to Th17 differentiation and function were identified based on previous studies. RNA-seq identified 12,893 genes with 2,851 genes with p-values <0.05 with distinct patterns of gene expression between male and female AS patients. TGF-β, PGE2, and S100 proteins were significantly upregulated in males. Levels of IL-12B, a Th17 inducer, were lower in males compared to females. Additionally, receptors of IL-6, 12, 23, TGF-β, and PGE2 were downregulated in males, except for IL-17RC, which was upregulated. Genes involved in Th17 differentiation showed differential expression between genders, with elevated expression of BATF, SOCS1, NKD2, and ARID5A in men and decreased expression of FOXO1. Transcriptomic analysis revealed that male AS patients exhibit distinct expression patterns of IL-17 pro-inflammatory genes, which may contribute to the phenotypic differences observed between genders in AS.

Costovertebral and costotransverse joint involvement in spondyloarthritis.

Costovertebral (CV), costotransverse (CTr), sternoclavicular (SC), and manubriosternal (MS) joints are impacted in spondyloarthritis (SpA) patients; however, clinical aspects of these involvements require additional evaluation. A total of 281 SpA patients who had undergone chest computed tomography (CT) for any reason between 2010 and 2020 were included in the study. SpA patients were divided into three groups, ankylosing spondylitis (AS), non-radiographic axial SpA, and psoriatic arthritis. Thirty age- and sex-matched rheumatoid arthritis (RA) patients and 30 non-rheumatic disease individuals were selected for comparison. An experienced radiologist reviewed 24 CV, 20 CTr, 2 SC, and 1 MS joints from a thorax CT for each patient. All joints were classified as: normal (0); suspicious (1), mild (2), moderate (3), or severe (4). Total CV and CTr joint scores differed between diseases (p < .001). Male AS patients had higher CV and CTr scores than female AS patients (male CV score: 52 [range 0-96] and CTr score: 22 [range 0-80]; female CV score: 20 [range 0-96] and CTr score: 12 [range 0-79]). Strong negative correlations were detected in AS patients between chest expansion and CV (r = -0.703 p = .007) and CTr (r = -0.763 p = .002) joint involvement; positive correlations between CV and CTr joints, and modified Stoke Ankylosing Spondylitis Spinal Score (p < .05); and no significant association for MS and SC joints. CV and CTr joint involvement on thorax CT was more severe in AS and negatively affected chest expansion. The use of thorax CT scans performed for other indications in the examination of these joints may be advantageous for the early beginning of rehabilitation programs targeted at maintaining chest mobility.

All-Cause and Cause-Specific Mortality in Psoriatic Arthritis and Ankylosing Spondylitis: A Systematic Review and Meta-Analysis.

Psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are chronic inflammatory diseases associated with a higher risk of cardiometabolic comorbidities compared to the general population. Individual studies examining mortality in these patients have produced conflicting results. The present study was undertaken to perform a systematic review and meta-analysis to analyze the all-cause and cause-specific mortality in PsA and AS from the available literature. A comprehensive database search was performed for studies reporting all-cause or cause-specific mortality in patients with PsA and AS compared with the general population. Pooled relative risks (RRs) were calculated using a random-effects model. We included 19 studies (11 of PsA, 7 of AS, 1 of both). In PsA studies, there was no increased mortality compared to the general population (RR 1.12 [95% confidence interval (95% CI) 0.96-1.30]; n=10 studies). We found a higher all-cause mortality in female (RR 1.19 [95% CI 1.04-1.36]) but not in male (RR 1.02 [95% CI 0.66-1.59]) PsA patients. Cardiovascular-, respiratory-, and infection-specific mortality risks were significantly higher for PsA patients (RR 1.21 [95% CI 1.06-1.38], RR 3.37 [95% CI 1.30-8.72], and RR 2.43 [95% CI 1.01-5.84], respectively), but not cancer-related mortality (RR 1.01 [95% CI 0.91-1.11]). In AS, we found a higher risk of death from all causes (RR 1.64 [95% CI 1.49-1.80]; n=6 studies) and cardiovascular causes (RR 1.35 [95% CI 1.01-1.81]; n=3 studies) compared to the general population. All-cause mortality was high in both male (RR 1.56 [95% CI 1.43-1.71]) and female (RR 1.85 [95% CI 1.56-2.18]) AS patients. The included AS studies did not report mortality data for non-cardiovascular causes. This systematic review and meta-analysis showed a significantly increased risk of overall mortality in AS but not PsA. Cardiovascular-specific mortality was higher for both PsA and AS, which emphasizes the importance of early screening and management of cardiovascular risk factors.

JAK-STAT signaling pathway-related gene single nucleotide polymorphisms and susceptibility to ankylosing spondylitis in eastern Chinese Han population.

A case-control study was utilized to investigate the relationship between genetic variation of JAK-STAT signaling pathway-related genes and the susceptibility to ankylosing spondylitis (AS). Fifteen SNPs in the JAK-STAT signaling pathway-related genes from 660 AS patients and 646 healthy controls were genotyped using iMLDR technology (JAK1: rs2230587, rs2230588, rs2780815, rs310241; JAK2: rs2274472, rs2230722, rs2230724, rs10758669; STAT1: rs10199181, rs1547550, rs2066802, rs45463799, rs6718902; STAT3: rs3744483; STAT5A: rs1135669). Allele analysis revealed that the T allele of STAT1 rs6718902 was a protective agent for male AS patients (OR = 0.765, 95% CI = 0.644-0.909). Inheritance models showed that GG + CG as well as GG genotypes of STAT1 rs1547550 had a significant risk of developing AS in males (OR = 5.374, 95%CI = 2.505-11.526; OR = 5.186, 95%CI = 2.412-11.153). The TT + CT and TT genotypes at STAT1 rs6718902 were observed to be associated with a significantly decreased risk of AS compared to CC genotypes among male patients and male controls (OR = 0.637, 95%CI = 0.485-0.837; OR = 0.597, 95%CI = 0.422-0.845). Furthermore, the genotypes of JAK1 gene rs2230588, rs2780815, and rs310241 were correlated with the severity of clinical conditions in female AS patients, while the JAK2 rs2230724 genotypes may affect disease ability in male AS patients. These findings indicated that JAK-STAT signaling pathway-related gene single nucleotide polymorphisms may be associated with AS susceptibility in eastern Chinese Han population. Key Points • The T allele of rs6718902 on the STAT1 gene may be a protective agent for male AS patients. • STAT1 rs1547550 GG + CG and GG genotypes were observed to be connected with a risk of male AS patients. However, STAT1 rs6718902 TT + CT and TT genotypes reduced the susceptibility risk of male AS patients compared to wild-type CC. • The JAK1 genes rs2230588, rs2780815, and rs310241 may affect disease functional status in female AS patients, while the JAK2 rs2230724 genotype was related to disease activity in male AS patients.

Malignancy in ankylosing spondylitis: a cross-sectional analysis of a large population database

BackgroundIncreased cancer-risk has been reported with rheumatoid arthritis and systemic lupus erythematosus, but the risk is poorly studied in ankylosing spondylitis (AS). Conflicting data in AS have been reported in Asia and Europe, with lack of US population-based studies. Our objective is to study the prevalence of cancer in patients with AS in the US.MethodsUsing the Explorys database, we performed a cross-sectional study. Data from AS patients and controls were stratified by 2 rheumatology visits, age groups, clinical characteristics, and frequency of cancers. The data were analyzed using a series of chi-square tests of independence as well as logistic regression to test for association between AS and cancer.Results1410 AS patients (12.88%) had cancer. Female AS patients had a lower prevalence of cancer compared to controls (OR 0.840, 95% CI [0.769, 0.916]), while male AS patients had no statistically significant difference (OR 1.011, 95% CI [0.929, 1.099]). Among patients with AS, Skin cancers (squamous cell, malignant melanoma, and basal cell) and head and neck cancers were significantly increased.ConclusionOur study demonstrated that the prevalence of “any-type-cancer” was not increased in AS patients compared to controls with no rheumatic disease. Skin, head, and neck cancers were more frequently seen in AS patients.

Increased proportions of inflammatory T cells and their correlations with cytokines and clinical parameters in patients with ankylosing spondylitis from northern Sweden.

Ankylosing spondylitis (AS) is an autoimmune disease affecting parts of the skeletal structure in particular. Previously increased levels of the inflammatory cell types Th17, Th22, Tc17 and Tc22 cells have been shown to be associated with AS. Here, we analysed the levels of inflammatory T cell subsets, related cytokines and clinical characteristics of AS patients vs controls from northern Sweden. Peripheral blood mononuclear cells (PBMCs) obtained from 50 AS patients and 50 matched controls were short term stimulated with PMA/Ionomycin, stained and analysed by flow cytometry. Plasma levels of Interleukin (IL)‐17, IL‐22, IL‐10 as well as clinically relevant markers were determined. Compared to male controls, male AS patients showed 1.5‐ to 2‐fold increases of Th17 (P = .013), Th22 (P = .003) and Tc22 (P = .024) among CD45+CD3+ lymphocytes. Plasma IL‐22 levels correlated with the Tc17 proportion in male patients (Rs = 0.499, P = .003) and plasma IL‐10 levels were inversely correlated with Tc17 among all patients (Rs = −0.276, P = .05). Male patients with syndesmophytes showed significantly higher Th17 proportions (P = .038). In female AS patients, Tc22 was negatively correlated with C‐reactive protein (high sensitivity) (hsCRP) (Rs = −0.573, P = .016). We confirmed increased proportions of inflammatory T cells and correlations with relevant cytokines from male AS patients. The correlation between Th17 and syndesmophytes supports a role of Th17 in the pathogenic process.

Disease activity in women with ankylosing spondylitis remains higher under Tumour Necrosis Factor inhibitor treatment than in men: a five-year observational study

Objective To assess sex differences in response, level of disease activity, and drug survival in tumour necrosis factor inhibitor (TNFi)-naïve ankylosing spondylitis (AS) patients. Method Consecutive AS patients, fulfilling the modified New York criteria, were included in a prospective cohort study at initiation of the first TNFi and followed until this medication was stopped (drug survival). Disease activity scores [AS Disease Activity Score using C-reactive protein (ASDAS-CRP), Bath AS Disease Activity Index (BASDAI), and CRP] were measured at 3, 6, and 12 months, and every subsequent year, up to 5 years. The response was defined by the ASDAS-CRP response criteria (clinically important improvement: ASDAS-CRP decrease ≥ 1.1). Analyses included regression methods for repeated measurements and survival analyses. Results Overall, 356 patients were included (34% women, mean ± sd age 46 ± 12 years), with a median disease duration of 12 (interquartile range 6;20) years. Women were less likely than men to achieve a clinically important response after 6 months of TNFi treatment (47% vs 64%; relative risk 1.4, 95% confidence interval (CI) 1.1;1.9, p = 0.02], despite a lack of sex differences in mean ASDAS-CRP levels over 5 year follow-up. Adjusted models for BASDAI over 5 years showed that women had a 0.6 point higher BASDAI score than men (β = 0.6 0.1;1.1 <0.02). Numerically, more women than men discontinued treatment over a period of 5 years (hazard ratio = 1.5, 95% CI 0.9;2.5, p = 0.15). Conclusion Female AS patients show a lower response to TNFi and a higher disease activity compared to men.

The usefulness of trabecular bone score in patients with ankylosing spondylitis.

Backgrounds/AimsThis study was performed to reveal the usefulness of the trabecular bone score (TBS) in assessing bone strength in patients with ankylosing spondylitis (AS) in comparison with dual-energy X-ray absorptiometry (DXA) methods.MethodsA total of 215 AS patients (75.8% male) were enrolled from a single university hospital in Korea. Demographic and clinical information were assessed. Patients completed X-rays of the cervical and lumbar spine (L-spine), and spinal ankyloses were quantified using the modified Stoke AS Spine Score (mSASSS). Hip, anteroposterior and lateral L-spine bone mineral density (BMD) and TBS were assessed by DXA methods. Clinical characteristics and bone strength measurement results were compared between male and female AS patients. The accuracy of each bone strength evaluation method in predicting Fracture Risk Assessment Tool (FRAX) scores indicating moderate or higher fracture risk was compared by receiver operating characteristic curves in patients aged ≥ 40 years. Correlations between each bone strength measurement method and mSASSS were examined.ResultsMale patients showed higher mSASSS and less prevalent peripheral joint involvement compared to female patients (p < 0.05). TBS, hip BMD, and L-spine lateral BMD showed comparably high areas under the curve (AUCs) for predicting FRAX-major osteoporotic fractures (MOF) ≥ 10% (AUC ranged 0.72 to 0.76). TBS negatively correlated with mSASSS in both male and female patients (p < 0.01).ConclusionsTBS could predict the risk of MOF and is not influenced by spinal osteoproliferation in AS patients, even in those with advanced spinal changes.

Trends in diagnostic prevalence and treatment patterns of male and female ankylosing spondylitis patients in the United States, 2006\u20132016

BackgroundThere has been much variation between epidemiological studies that report the prevalence of ankylosing spondylitis (AS). This study aimed to analyze the diagnostic prevalence rates and treatment patterns of male and female AS patients in the United States adult insured population from 2006 to 2016.MethodsTrends in AS prevalence were calculated for the 11-year period covering January 1, 2006 to December 31, 2016. Adult (18+ years old) AS patients were included in this retrospective analysis of medical and pharmacy claims data from the IBM Marketscan Commercial, Medicaid and Medicare-Supplemental Claims database. Prevalence was determined as having ≥1 AS diagnostic codes (ICD-9:720.0; ICD-10:M45.x). Trends in treatment patterns were also analyzed and stratified by gender.ResultsThe AS prevalence increased from 0.04 to 0.09% from 2006 to 2016. The mean age between 2006 and 2016 ranged from 49.52–50.00 years. In 2006, approximately 40% of AS patients were female, while in 2016 over 47% of AS patients were female. Rates of use of TNF inhibitors and oral glucocorticoids increased, while NSAIDs and non-biologic DMARDs (sulfasalazine & methotrexate) rates decreased. Opioid use rates were stable. In 2016, males were more likely to be prescribed biologics, while females were more likely to be prescribed methotrexate, sulfasalazine, NSAIDs, muscle relaxants, anticonvulsants, opioids, and glucocorticoids.ConclusionsThe prevalence of AS diagnosis codes more than doubled between 2006 and 2016, but the very low prevalence suggests that AS continues to be underdiagnosed and under-addressed in routine clinical practice. Despite the increase in female AS patients, females were less likely to be prescribed biologics compared to male AS patients.

Pregnancy in ankylosing spondylitis: the view of a female patient and a physician

Objective : to study the impact of the diagnosis of ankylosing spondylitis (AS) on the planning of pregnancy by patients and their attitude towards the use of drugs during gestation and to assess the competency of physicians in the issues relating to pregnancy in AS. Patients and methods . The data of three studies based on the questionnaire surveys of female AS patients and rheumatologists. Results and discussion . The questionnaire survey revealed a decline in the number of pregnancies per woman after the onset of AS. Having learned about their diagnosis, 70% of patients reported a change in their maternity plans; however, most (80%) women said that they were still going to become pregnant, but they would constantly feel discomfort and fear for their own health and the health of their future child. Pregnancy was rejected due to AS development by 13.9% of patients, regardless of the presence or absence of children born in the healthy period of their life. Only 50% of women discussed the issues relating to pregnancy with a rheumatologist, and one third of them did not obtain the necessary information. Only one fourth of patients were ready to continue treatment for AS in the period of preparation for conception and during gestation. On the whole, Russian rheumatologists have enough knowledge about pregnancy outcomes in AS, and, in particular, about the factors which may influence the favorable outcome and about the fundamentals of follow-up for pregnant women. At the same time, 18% of rheumatologists expect increased AS activity during gestation, more than two thirds consider sacroiliitis to be an indication for surgical delivery, and 30% are ready to discontinue the drugs which are permitted for use before pregnancy. Conclusion . Lack of information about the planning and course of pregnancy in AS, the risk of disease exacerbation and the safety of therapy during gestation is noted in both patients and rheumatologists. It is necessary to implement educational measures on the problem of pregnancy in AS for rheumatologists and women of fertile age and their family members.

GC-MS-based fecal metabolomics reveals gender-attributed fecal signatures in ankylosing spondylitis

Ankylosing spondylitis (AS) has different clinical features in males and females. Fecal metabolites play significant roles in AS disorders. This study aimed to reveal gender-attributed fecal signatures of AS. Fecal samples from 87 cross-sectional individuals (healthy controls: 20 males, 18 females; AS patients: 26 males, 23 females) were analyzed by gas chromatography-mass spectroscopy (GC-MS). Partial least squares discriminant analysis (PLS-DA) was used to reveal differences in the fecal signatures of AS between males and females. Fecal signatures were defined by the significantly different fecal metabolites between AS patients and healthy individuals. Therefore, different fecal signatures of male and female AS patients were defined as gender-attributed fecal signatures. Male-specific fecal signatures in AS patients were steroid compounds, including cholestan-3-ol, tocopherol, stigmastan-3,5-diene, cholest-3-ene, cholest-4-en-6-one and 1-heptatriacotanol. Female-specific fecal signatures were ergost-5-en-3-ol, acetate and D-myo-Inositol. Gender-attributed fecal signatures of AS further reveal differences between males and females in terms of AS features.

Persistence, Discontinuation, and Switching Patterns of Newly Initiated TNF Inhibitor Therapy in Ankylosing Spondylitis Patients in the United States.

IntroductionThe primary goals of treating ankylosing spondylitis (AS) patients are to maximize long-term health-related quality of life through control of symptoms and inflammation, prevention of progressive structural damage, and preservation of function. The objective of this study was to describe treatment patterns (persistence, discontinuations, and switch) in the 2 years following the initiation of tumor necrosis factor inhibitors (TNFi) therapy in AS patients.MethodsAdult patients with ≥ 2 AS diagnostic codes (ICD-9: 720.0 and/or ICD-10:M45.x) by a healthcare provider were included in this retrospective analysis of data from the IBM MarketScan Commercial Claims database. Patients who newly initiated a TNFi from 01/01/2009 to 12/31/2013 were indexed on their first TNFi. Patients were required to have a 1-year pre-index period free of TNFi and continuous enrollment 1-year pre-index and 2-year post-index. Patients were excluded if they had ≥ 2 diagnostic codes for any of the following conditions: rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, Crohn’s disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa, or uveitis. Demographic, clinical, and treatment patterns were analyzed. Treatment patterns included switching to a new TNFi, discontinuation (≥ 90-day gap in therapy without starting a new TNFi), or persistence (no gaps in therapy ≥ 90 days) during the 2-year follow-up period. Logistic regression analyses predicting persistent vs. non-persistent and switching vs. discontinuation were conducted.ResultsA total of 1372 AS patients (846 males/526 females) met the inclusion criteria for this study. Males had a mean age of 44.3 years, while females had a mean age of 42.3 years. Adalimumab was the first biologic for the majority of patients (44.6% males/43.3% females), followed by etanercept (40.4% males/41.6% females), infliximab (10.4% males/10.8% females), golimumab (4.6% males/3.8% females), and certolizumab pegol (0.0% males/0.4% females). During the follow-up period, 33.1% of patients (n = 454) were persistent on their index TNFi, 40.7% (n = 559) discontinued their index TNFi and did not restart a TNFi, and 26.1% (n = 359) switched to a second TNFi. Patients prescribed cDMARDs were more likely to be persistent, while females and opioid users were less likely to be persistent on their first TNFi. Among those that discontinued their first TNFi, 32.8% (n = 187) of males and 43.6% (n = 177) of females switched to a second TNFi.ConclusionsThis study suggests that approximately 67% of male AS patients and 77% of female AS patients newly initiating a TNFi do not remain on the index therapy 2 year post initiation.FundingEli Lilly and Company.

Although female patients with ankylosing spondylitis score worse on disease activity than male patients and improvement in disease activity is comparable, male patients show more radiographic progression during treatment with TNF-α inhibitors

BackgroundThe clinical presentation of ankylosing spondylitis (AS) differs between genders. Our aim was to investigate differences in disease activity, disease outcome and treatment response between male and female AS patients before and after starting tumor necrosis factor (TNF)-α inhibitors in daily clinical practice. MethodsPatients from the Groningen Leeuwarden AS (GLAS) cohort who started TNF-α inhibitors and who had visits at baseline and after 3 months and/or 2years of follow-up were included. ResultsOf 254 included AS patients, 69% were male. At baseline, female patients scored significantly higher on BASDAI, ASDAS, and tender entheses than male patients. In contrast, CRP, swollen joints, and history of extra-articular manifestations were comparable between genders. Women experienced significantly worse physical function and QoL, whereas men showed significantly more kyphosis and spinal radiographic damage. After 3 months and 2years of follow-up, all clinical assessments improved significantly, with comparable mean change scores for female and male patients; mean 2-year change in BASDAI -2.7 vs. -2.7, ASDAS -1.50 vs. -1.68, tender entheses -2.4 vs. -1.4, CRP -8 vs. -8, BASFI -2.2 vs. -2.1 and ASQoL -5 vs. -4, respectively. Radiographic progression was significantly higher in male patients. Female patients switched more frequently to another TNF-α inhibitor during 2years of follow-up (32% vs. 14%). ConclusionAlthough female patients experienced higher disease activity, worse physical function and quality of life, and switched TNF-α inhibitors more often, clinical improvement during treatment with TNF-α inhibitors was comparable between genders. However, male patients showed more radiographic spinal damage after 2years.

Risk Factors of Renal Involvement Based on Different Manifestations in Patients with Ankylosing Spondylitis

Background/Aims: Renal involvement is one of the most common extra-articular complications caused by ankylosing spondylitis (AS). Most studies have focused on the incidence rate, clinical manifestation and pathology, while risk factors have hardly been investigated. Therefore, the objective of this study was to assess the risk factors of renal involvement in patients with AS. Methods: Clinical and biochemical data of 926 AS patients were collected. Based on the manifestations of renal involvement, patients were divided into three groups and the differences in clinical and biochemical characteristics were compared. A group with non-renal involvement served as a control. Multivariable logistic regression was used for analyzing risk factors of renal involvement in AS. Results: Of the 926 AS patients, 201 patients suffered from renal involvement. Moreover, female AS patients faced a higher risk of hematuria compared to male patients. As indicated by the data obtained from multivariate logistic regression analysis, gender, uric acid (UA), immunoglobulin A (IgA), and serum albumin (ALB) were found to be risk factors of renal involvement in AS. An increase in UA or IgA levels, or a decrease in ALB level can increase the risk of renal involvement with multiple manifestations (more than one manifestation of renal damage). According to our findings, no definite variable was identified as a risk factor of proteinuria in AS patients. Conclusion: In AS patients, UA, IgA, and ALB levels can indicate the risk of renal involvement in AS patient and need to be paid special attention. Furthermore, women are subjected to a higher risk of hematuria.

Single nucleotide polymorphisms of autophagy-related 16-like 1 gene are associated with ankylosing spondylitis in females: a case-control study.

To investigate the associations of autophagy-related 16-like 1 (ATG16L1) gene single nucleotide polymorphisms (SNPs) with ankylosing spondylitis (AS) in a Chinese Han population. Six hundred and forty-nine AS patients from the First Affiliation Hospital of Anhui Medical University and 628 matched controls were selected. Genotyping for five SNPs in the ATG16L1 gene (rs4663421, rs2241880, rs4663396, rs6758317 and rs6431655) was performed using the improved multiplex ligase detection reaction (iMLDR) method. Haplotypes were built after linkage disequilibrium (LD) analysis. All analyses were stratified by gender. Significant differences in the genotype frequencies at rs4663421 were found between female AS patients and female controls (P=0.033). The frequencies of allele G of rs4663421 and allele C of rs6758317 were lower in AS patients than controls (odds ratio [OR]=0.391, 95% CI=0.175-0.876, P=0.019; OR=0.499, 95% CI=0.263-0.949, P=0.032, respectively) in females. However, no association remained significant after Bonferroni correction. rs4663396 and rs6758317 have been tested in high LD, and were used to construct three haplotypes: ht1 (CC), ht2 (TT) and ht3 (CT). The frequency of ht2 (TT) haplotype was higher in AS patients than controls (OR=2.003, 95% CI=1.053-3.808, P=0.032) in females; similarly, no association existed after Bonferroni correction. Two SNPs (rs4663421 and rs6758317) and the TT haplotype of the ATG16L1 gene are possibly associated with AS susceptibility in a Chinese Han female population.

Are ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis associated with an increased risk of cardiovascular events? A prospective nationwide population-based cohort study

BackgroundTo investigate the risk of first-time acute coronary syndrome (ACS), stroke and venous thromboembolism (VTE) in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA) and undifferentiated spondyloarthritis (uSpA), compared to each other and to the general population (GP).MethodsThis is a prospective nationwide cohort study. Cohorts with AS (n = 6448), PsA (n = 16,063) and uSpA (n = 5190) patients and a GP (n = 266,435) cohort, were identified 2001–2009 in the Swedish National Patient and Population registers. The follow-up began 1 January 2006, or 6 months after the first registered spondyloarthritis (SpA) diagnosis thereafter, and ended at ACS/stroke/VTE event, death, emigration or 31 December 2012. Crude and age- and sex-standardized incidence rates (SIRs) and hazard ratios (HRs) were calculated for incident ACS, stroke or VTE, respectively.ResultsStandardized to the GP cohort, SIRs for ACS were 4.3, 5.4 and 4.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort, respectively, compared to 3.2 in the GP cohort. SIRs for stroke were 5.4, 5.9 and 5.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort compared to 4.7 in the GP cohort. Corresponding SIRs for VTE were 3.6, 3.2 and 3.5 events per 1000 person-years at risk compared to 2.2 in the GP cohort. Age-and sex-adjusted HRs (95% CI) for ACS events were significantly increased in AS (1.54 (1.31–1.82)), PsA (1.76 (1.59–1.95)) and uSpA (1.36 (1.05–1.76)) compared to GP. Age-adjusted HRs for ACS was significantly decreased in female AS patients (0.59 (0.37–0.97)) compared to female PsA patients. Age-and sex-adjusted HRs for stroke events were significantly increased in AS (1.25 (1.06–1.48)) and PsA (1.34 (1.22–1.48)), and nonsignificantly increased in uSpA (1.16 (0.91–1.47)) compared to GP. For VTE the age-and sex-adjusted HRs for AS, PsA and uSpA were equally and significantly increased with about 50% compared to GP.ConclusionsPatients with AS, PsA and uSpA are at increased risk for ACS and stroke events, which emphasizes the importance of identification of and intervention against cardiovascular risk factors in SpA patients. Increased alertness for VTE is warranted in patients with SpA.

Targeting the interleukin-23/17 axis in axial spondyloarthritis.

This article highlights and emphasizes how new knowledge of mechanisms linked to the interleukin-23 (IL-23)/IL-17 pathway is relevant to the pathophysiology of axial spondyloarthritis (axSpA) and demonstrates how molecules in IL-23/IL-17 pathway provide novel therapeutic targets for axSpA patients. Similarly to ankylosing spondylitis (AS), the increased frequency of Th17 cells in nr-axSpA patients underscores the concept that these disorders can be viewed on a spectrum. Recent findings suggest that the contribution of IL-23/IL-17 signaling pathways possibly differs in male and female AS patients. The finding that IL-17 and IL-22 secreting-type 3 innate lymphoid cells are increased in AS patients point to their potential role in the pathogenesis of axSpA. Reports of dysbiosis in the gut microbiome of AS patients support previous work indicating a possible causal relationship between altered gut flora, ileocolonic inflammation and axSpA. Of important clinical relevance are results from clinical trials supporting the efficacy and safety of agents that block IL-12/23 (ustekinumab) and IL-17 (secukinumab and ixekizumab) in AS patients. Recent studies further establish the central position of the IL-23/IL-17 pathway in the pathogenesis of axSpA. Targeting the IL-23/IL-17 pathway appears to be a safe and effective strategy for treatment of axSpA patients.

Evaluation of Sexual Dysfunction in Females With Ankylosing Spondylitis.

This study aims to evaluate sexual function in females with ankylosing spondylitis (AS), compare them with healthy controls, and demonstrate the effects of AS on female sexual functions. Fifty-four AS patients (mean age 39.33±8.57 years; range 20 to 55 years) and 56 similar aged healthy controls were included in the study. Depression levels and sexual functions of all participants were evaluated by the Beck Depression Inventory and Female Sexual Function Index (FSFI), respectively. Other assessment methods included the visual analog scale for pain, fatigue, and importance of sexual life; Bath Ankylosing Spondylitis Disease Activity Index for disease activity, Bath Ankylosing Spondylitis Functional Index for functionality, Bath Ankylosing Spondylitis Metrology Index for spinal mobility, and Short Form-36 (SF-36) for quality of life. Total FSFI and all FSFI subscale scores and number of weekly sexual intercourse were significantly lower while Beck Depression Inventory score was significantly higher in females with AS when compared to controls. In AS patients with depression, total FSFI score and FSFI subscales scores of desire and arousal were significantly lower than those without depression. In females with AS, there were negative correlations between total FSFI score and duration of complaint, Beck Depression Inventory score, Bath Ankylosing Spondylitis Metrology Index score, visual analog scale score, age, and duration of marriage while positive correlations existed between total FSFI score and visual analog scale importance of sexual life score and number of weekly sexual intercourse, SF-36 fatigue, SF-36 social function, SF-36 pain, and SF-36 mental component scores. Sexual dysfunction was more common in female AS patients without marked impairment in body image and hip involvement when compared to normal population. Sexual problems which are generally neglected should be handled regardless of disease activity when evaluating patients with AS and establishing a treatment plan.

Investigating the effects of a multidimensional exercise program on symptoms and antiinflammatory status in female patients with ankylosing spondylitis

ObjectiveThe purpose of this study is to investigate the effects of a multidimensional exercise program on symptoms and antiinflammatory status in female patients with ankylosing spondylitis (AS). MethodsThe BATH Indexes, Dougados Functional Index (DFI), Health Assessment Questionnaire in Spondyloarthopathies (HAQ-S), Ankylosing Spondylitis Quality of Life (ASQoL) and Beck Depression Inventory (BDI) were used to evaluate twenty-four female AS patients. ESR, CRP, TNF-α and IL-6 were also analyzed. All patients were assessed at baseline and with 3 weeks intervals till 12 week. A multidimensional exercise program was applied for three times a week. ResultsThere were significant differences in Bath Ankylosing Spondylitis Global Index (BAS-G) and Disease Activity Index (BASDAI), HAQ-S, ASQoL and BDI scores (p < 0.05). The level of the ESR, CRP and IL-6 fluctuated slightly. There was only significant difference at 3 and 12 weeks as compared to baseline levels in TNF-α values (p = 0.048, p < 0.001). ConclusionWe concluded that multidimensional exercise program should be taken into consideration for AS patients due to its positive effects on symptoms and antiinflammatory effects.