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Background: Patients with chronic medical disorders are substantially more likely to have sleep related issues. Previously, various authors have reported sleep disruptions to be common in rheumatic diseases, although such sleep related issues in the spondyloarthropathies have not received much attention.. Aim: The present study was aimed to assess the effect of spondyloarthropathies on sleep quality and to see whether this effect is associated with disease activity. Material and Methods: This cross-sectional study was conducted in the rheumatology clinic, King Khalid University Hospital, during the duration of two months. A total of 85 diagnosed cases of spondyloarthritis were included. All participants were interviewed regarding their Demographic details, disease duration, medications, treatment regimens and physical examination. Sleep disturbance was measured using Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index, and the Ankylosing Spondylitis Quality of Life scale. The intensity of disease activity was evaluated using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and patient’s functional status was evaluated using the Bath Ankylosing Spondylitis Functional Index (BASFI). Blood inflammatory markers like ESR levels and CRP levels were also calculated for each patient. Results: Among the total 79 cases included, mean age of patients was 41.06±11.78 years, 40 (50.6%) were females, mean disease duration was 5 years. Diagnoses included Ankylosing spondylitis (48.10%), Psoriatic arthritis (43.04%), Undifferentiated spondyloarthopathy (6.33%) and IBD-related arthropathy (2.53%). Spondyloarthritis was observed to be associated with considerable impaired sleep quality on (PSQI) questionnaire. Six out of seven studied components came out to be worse and the only component which remained unaffected was “use of sleep Medication”. A significant correlation was observed between disease severity and patients ESR and CRP levels, and a significant correlation was observed between BASDAI score and all seven sleep quality parameters and overall PSQI scores. Both BASDAI score and BASFI scores correlated significantly with each other and a significant correlation was observed between the functional status (BASFI score) and Six sleep quality parameters except for use of sleep medication. Conclusion: We conclude that the sleep related problems were significantly higher in patients with spondyloarthritis and patients during active phase of disease had decreased sleep quality. Keywords: spondyloarthropathies, sleep quality, disease activity, PSQI scores.

Objective To systemically review all clinical trials that evaluate the effectiveness of orthodontic intrusion using bone anchorage devices versus using other orthodontic techniques in adult patients. Material and methods All randomized, controlled clinical trials and prospective studies that compare the use of TADs in intrusion versus alternative devices from the year 2000 to 2019 were searched using various electronic databases. Databases used include Pubmed, Cochrane, Scopus, Lilacs, and ScienceDirect. Selection was initially made by reading the titles and abstracts of potential suitable studies. The final selection was made after reading the full retrieved articles. A methodological score developed by Lagravere was used to assess the quality of evidence. The selection process was illustrated using a PRISMA flow chart. Results A total of 3942 articles were retrieved, from which only two randomized clinical trials met the inclusion criteria. This presented a low to medium level of evidence to support the hypothesis that TADs are more effective than other orthodontic intrusion techniques for intruding upper incisors and improving upper incisor to lip relation while eliminating the adverse effect of compromising vertical posterior anchorage. Shorter treatment times and less root resorption were found in the TAD group. Conclusion There is insufficient evidence to state that TADs can be used as orthodontic anchorage to effectively intrude the incisors without the need for patient cooperation. Future high quality prospective randomized clinical trials are required.

Highlights • This scoping review provides an up-to-date overview of published evidence regarding the frequency and severity of acute viral respiratory AEs related to antirheumatic disease therapies. • Glucocorticoid use was associated with a higher frequency of acute upper and lower respiratory viral events. • Mild viral respiratory infections occurred more frequently in several studies in which patients were treated with JAKi, most notably at higher doses. • TNFi and IL-17 inhibitors seemed to be associated with higher frequency of mild viral respiratory infections such as URTI and nasopharyngitis. • Our review identifies a knowledge gap for most antirheumatic medications and their acute respiratory viral complications; in the context of the COVID-19 pandemic, increased widespread respiratory viral PCR testing offers immediate research opportunities to clarify the safety of antirheumatic therapies in terms of viral respiratory complications., Introduction COVID-19 is an acute respiratory viral infection that threatens people worldwide, including people with rheumatic disease, although it remains unclear to what extent various antirheumatic disease therapies increase susceptibility to complications of viral respiratory infections. Objective The present study undertakes a scoping review of available evidence regarding the frequency and severity of acute respiratory viral adverse events related to antirheumatic disease therapies. Methods Online databases were used to identify, since database inception, studies reporting primary data on acute respiratory viral infections in patients utilizing antirheumatic disease therapies. Independent reviewer pairs charted data from eligible studies using a standardized data abstraction tool. Results A total of 180 studies were eligible for qualitative analysis. While acknowledging that the extant literature has a lack of specificity in reporting of acute viral infections or complications thereof, the data suggest that use of glucocorticoids, JAK inhibitors (especially high-dose), TNF inhibitors, and anti-IL-17 agents may be associated with an increased frequency of respiratory viral events. Available data suggest no increased frequency or risk of respiratory viral events with NSAIDs, hydroxychloroquine, sulfasalazine, methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, or apremilast. One large cohort study demonstrated an association with leflunomide use and increased risk of acute viral respiratory events compared to non-use. Conclusion This scoping review identified that some medication classes may confer increased risk of acute respiratory viral infections. However, definitive data are lacking and future studies should address this knowledge gap.

Background Methotrexate (MTX) Intolerance Severity Score (MISS) has been previously validated in the Arabic language and has helped to detect high levels of intolerance in rheumatoid arthritis (RA) patients. The aim of the current study was to evaluate patient and disease characteristics associated with a high risk of MTX intolerance. Materials and methods A cross-sectional interview-based survey was conducted using adult RA patients as a study group, who were visiting a specialized rheumatology clinic at King Saud University Medical City. The Arabic MISS was used in this survey. Statistical analyses were performed to understand associations between MTX-intolerant and MTX-tolerant patients. Results A total of 117 patients were involved in this study. Of those, 101 (86.3%) were females with a mean (SD) disease duration of 6.6 (5.7) years. The median (interquartile range (IQR)) Disease Activity Score-28 (DAS28) was 3.6 (3.6-4.1). MTX intolerance was observed in 55 (47%) patients. The most predominant component in patients with a positive test was the behavioral component. Intolerant patients had a higher median of pain (47.3 vs. 50.0; P = 0.010) and patient global assessment (50.0 vs. 60.0; P = 0.004) scales compared to those in tolerant patients. Additionally, MTX intolerance was associated with the female gender (adjusted odds ratio (AOR) 6.724; 95% CI 1.420, 31.843, P = 0.016), marital status (AOR 2.549; 95% CI 1.037, 6.270, P = 0.042) and DAS28 (AOR 1.612; 95% CI 1.032, 2.517, P = 0.036). There was no significant difference between the two groups in the remaining disease activity parameters, background therapies, seropositivity, and smoking status (P > 0.05). Conclusion Patient characteristics, rather than disease activity, significantly impact MTX intolerance. Behavioral component is the main driver of intolerance. Intolerant patients have higher patient-reported outcomes. Qualitative studies are needed to explore causes and potential solutions to MTX intolerance.

Observational studies allow researchers to understand the natural history of rheumatic conditions, risk factors for disease development, and factors affecting important disease-related outcomes, and to estimate treatment effect from real-world data. However, this design carries a risk of confounding bias. A propensity score (PS) is a balancing score that aims to minimize the difference between study groups and consequently potential confounding effects. The score can be applied in 1 of 4 methods in observational research: matching, stratification, adjustment, and inverse probability weighting. Systemic lupus erythematosus (SLE) is a rare disease characterized by a relatively small sample size and/or low event rates. In this article, we review the PS methods. We demonstrate application of the PS methods to achieve study group balance in a rare disease using an example of risk of infection in SLE patients with hypogammaglobulinemia.

Background COVID-19 is diagnosed using RT-PCR assays of samples from nasal and oropharyngeal swabs. People with negative RT-PCR often presented with clinical manifestations of COVID-19. The data on such patients are lacking. The present study aims to characterize the patients who were suspected COVID-19 cases and tested negative in RT-PCR compared to patients who had been tested RT-PCR positive. Methods This is a retrospective, observational study of adult suspected and confirmed patients of COVID-19 admitted to King Saud University Medical City, Riyadh, Saudi Arabia, from 1st March 2020 until 30th November 2020. Laboratory confirmation is done through nasal/pharyngeal swab specimens, tested positive in RT-PCR assay. Patients with initial negative RT-PCR test results were assessed again within 48−72 h to avoid false-negative results. Patient data were extracted from the electronic medical files of each included patient using a predesigned case report form. Results The study included 488 (80.93%) patients with RT-PCR swab results positive, and 115 (19.07%) patients who were negative. Respiratory rate and diastolic blood pressure were higher among the swab-positive cases. More number of swab-negative patients had comorbidities such as coronary heart disease, chronic kidney disease, and carcinoma. Fever, cough, and shortness of breath were reported higher among the swab-positive cases. ALT and AST, and LDH levels were found higher among RT-PCR-positive patients. Serum creatinine, blood urea nitrogen and troponin were more elevated in RT-PCR-negative patients. Antibiotics, anticoagulants, and corticosteroids were used more by swab-positive patients. Significantly higher number of RT-PCR-positive patients required proning, high-flow nasal cannula, non-invasive mechanical ventilation, and invasive mechanical ventilation. Acute cardiac ischemia and death were found to be similar among the patients. However, deaths occurred significantly earlier among the swab-positive cases when compared to the swab-negative group. Conclusion Distinctive symptoms and markers of COVID-19 are more frequent among patients who had RT-PCR-positive results.

Mohammed A Omair,1 Fatima Al Suwayeh,2 Alanoud Almashaan,2 Eman Alqurtas,1 Mohammed K Bedaiwi,1 Ibrahim Almaghlouth,1 Abdulaziz Alkahalaf,1 Haya M Almalaq2 1Rheumatology Unit, Department of Medicine, King Saud University, Riyadh, Saudi Arabia; 2Clinical Pharmacy Department, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Mohammed A OmairRheumatology Division, Department of Medicine (38), College of Medicine King Saud University, PO Box 2925, Riyadh, 11461, Saudi ArabiaTel/Fax +966-1-467-1546Email momair@ksu.edu.saPurpose: A simple measure to assess drug adherence in Saudi patients with rheumatoid arthritis (RA) is required. The aim of this study was to translate and validate the 5-Item Compliance Questionnaire for Rheumatology (CQR5) into Arabic.Patients and Methods: The questionnaire was translated and culturally adapted to Arab patients in six steps: initial translation, synthesis of the translation, back translation, expert committee review, test of the pre-final version, and development of the Arabic CQR5 (ACQR-5). The resulting version was tested for validity in patients with RA.Results: A total of 103 adult patients with RA were recruited from rheumatology clinics at a university hospital in Riyadh, Saudi Arabia. After extensive translation, the final tool (CQR) was piloted in 15 patients. The final validation was performed with 88 patients. Of these, 80 (90.9%) were female and 43.2% were seropositive. The mean (±SD) age and disease duration were 50 (± 13) and 11.4 (± 8.2) years, respectively. Cronbach’s alpha reliability was 0.886, and the Kaiser-Meyer-Olkin measure of sampling adequacy for factor analysis was 0.870 (p< 0.001). The mean ACQR-5 was 17.78 (2.70), with 14 (15.9%) classified as low adherents and the remaining 74 (84.1%) as high adherents. Binary logistic regression revealed that increasing age (odds ratio [OR] 1.082, 95% confidence interval [CI]: 1.025– 1.142, p=0.005) and a trend toward the presence of other comorbidities (OR 3.111, 95% CI: 0.961– 10.070, p=0.058) were associated with low adherence.Conclusion: ACQR-5 is a simple and feasible tool for identifying adherence levels in patients with RA in Saudi Arabia. A high level of adherence was observed in this study. Additional studies are required to assess ACQR-5 validity and adherence levels in a larger, more diverse population.Keywords: adherence, rheumatoid arthritis, compliance questionnaire for rheumatology, Saudi Arabia

Immunoglobulins play a fundamental role in the protection of the human body against internal and external threats. They also contribute to the immune system homeostasis and maintenance of self-tolerance. Hypogammaglobulinemia is occasionally encountered in routine clinical practice by rheumatologists. Low levels of immunoglobulins can occur as primary or secondary issues and may predispose patients to various forms of infection. However, the impact of the low immunoglobulin level abnormality varies with the underlying condition. In this narrative review, we shed light on the overall types and functions of immunoglobulins for clinicians. We discuss important principles of immunoglobulin measurements. We then consider the primary and secondary causes of low immunoglobulins with a special focus on hypogammaglobulinemia in patients with systemic lupus erythematosus (SLE).

Systemic Lupus erythematosus (SLE) is a chronic multisystem, multifactorial inflammatory autoimmune disease. The SLE patients have 3 times increased risk of mortality based on international data with ethnicity playing an important impact on patients’ morbidity and mortality. Descriptive studies from Saudi Arabia showed variation in clinical features from one region to another. Moreover, reliable inference from these studies is limited by study methodology and lack of translational data using biological samples to understand clinical phenotypes of Saudi SLE patients. The aim of this report is to describe the prospective study protocol of the National Systemic Lupus Erythematosus Cohort in Saudi Arabia. The purpose of this cohort study is multifold: first, to examine clinical characteristics and molecular phenotypes of Saudi SLE patients in relation to local environment and practices/lifestyles; second, to assess long-term outcomes of SLE in Saudi population and factors that influence favorable outcomes; third, to compare the effectiveness of various treatment regimens in Saudi SLE population. This study is a longitudinal prospective cohort study of adult, Saudi SLE patients using open cohort study design. Primary outcomes include disease-related outcomes (activity, improvement, and organ damage) and patient-reported outcomes (quality of life). Secondary outcomes include physiological and molecular modifications associated with changes in disease activity states.Results and analysis are in on-going study. This study provides a source of reliable data for clinical and translational research. This will allow us to have a holistic approach to SLE pathogenesis especially in Saudi population and may take us a step further toward much more personalized medicine. This protocol has been registered in NIH ClinicalTrial.gov (ClinicalTrial.gov identifier: NCT04604990) on October 27, 2020.

Objectives: To map research production by Saudi-affiliated investigators in order to identify areas of strength and weakness. Method: We followed the Arksey and O’Malley (2005) framework. Medline and Cochrane databases were searched with a focus on identifying articles related to COVID-19 and Saudi Arabia following the PRISMA protocol. The study was conducted at King Saud University, Riyadh, Saudi Arabia between March and May 2020. Results: A total of 53 articles were ultimately included. Most of the research production from Saudi Arabia was opinion and narrative reviews related to the clinicopathological features of COVID-19 as well as control and prevention of virus spread. Conclusion: The results of this scoping review identify a relative deficiency in original research, which requires further investigation. Saudi Med J 2020; Vol. 41 (8): 791-801 doi: 10.15537/smj.2020.8.25163 How to cite this article: Ibrahim Almaghlouth, Tahera Islam, Nurah Alamro, Abdulrahman Alsultan, Assim Alfadda, Saleh Al-muhsen, Abeer Almasry, Majid A Almadi, Ahmad Hersi, Ahmed BaHammam. Mapping COVID-19 related research from Saudi Arabia, a scoping review. Between reality and dreams. Saudi Med J 2020; Vol. 41 (8): 791-801. doi: 10.15537/smj.2020.8.25163

AIM: The dynamics of coronavirus disease 2019 (COVID-19) pandemic has become of special concern to the rheumatology community. Rheumatic patients are required to engage in effective health management but their behavior is often influenced by intrinsic and extrinsic factors. This cross-sectional study aims to examine patients' experiences during the current pandemic and its implication on their health perception and behavior. METHOD: A patient-centered electronic survey was used, randomly sampling rheumatic patients in Saudi Arabia during March and April 2020. Questions included patients' socio-demographics, diseases, medications, COVID-19 knowledge, source of information, fear level, disease activity perception, health care utilization, medication accessibility, and therapeutic compliance (measured using a modified version of Medication Adherence Reporting Scale). Correlation and regression coefficients were used to evaluate associations among the aforementioned variables. RESULTS: A total of 637 respondents were included. The majority were rheumatoid arthritis patients (42.7%). Patients' knowledge about COVID-19 was correlated with social media use (P = .012). Fear of COVID-19 infection correlated with healthcare facility for follow-up visits (P = .024) and fear of disease deterioration if contracting the infection correlated with patients' levels of knowledge (P = .035). Both types of fear did not correlate with patients' perceptions of disease activity. However, patients' perceptions of worsened disease activity were correlated with unplanned healthcare visits (P < .001), medication non-adherence, and difficulty accessing medication (P = .010 and .006, respectively). CONCLUSION: The COVID-19 pandemic and surrounding public health measures could affect rheumatic patients' health management which might contribute to disease flare-up and subsequently taxing healthcare systems even further.

OBJECTIVE: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), manifests with a wide spectrum of presentations. Most reports of COVID-19 highlight fever and upper respiratory symptoms as the dominant initial presentations, consistent with the World Health Organization guidelines regarding suspected SARS-CoV-2 infection. However, atypical presentations of this disease have been evolving since the initial outbreak of the pandemic in December 2019. We report a case of an older male patient who presented at our hospital with an unusual manifestation of COVID-19. DESIGN: Brief report. SETTING: A university hospital in Saudi Arabia. PARTICIPANT: A 73-year-old man who presented with confusion in the absence of any respiratory symptoms or fever. INTERVENTION: The patient was initially admitted with delirium and underwent a further work-up. MEASUREMENTS: Given his recent history of domestic travel and the declaration of a global COVID-19 pandemic status, the patient was administered a swab test for SARS-CoV-2. RESULTS: The patient's positive test led to a diagnosis of COVID-19. Although he began to experience a spiking fever and mild upper respiratory symptoms, he recovered rapidly with no residual sequela. CONCLUSION: The recognition of atypical presentations of COVID-19 infection, such as delirium, is critical to the timely diagnosis, provision of appropriate care, and avoidance of outbreaks within healthcare facilities during this pandemic. J Am Geriatr Soc 68:1382-1384, 2020.

Objective Infection is a leading cause of death in the SLE population. Low immunoglobulin levels might be a potential risk for infection. We aimed to assess whether acquired low levels of any type of immunoglobulin increase the risk of clinically relevant infection in adult patients with SLE. Methods We compared adult SLE patients who had acquired any low immunoglobulin levels (IgA, IgM or IgG) for 2 years with patients with normal or high levels with respect to clinically relevant infection (defined as infections requiring intravenous or oral antibiotics) in a prospective cohort study. Group balance was achieved using propensity score adjustment, matching and inverse probability weighting. Primary analysis was time to event using Cox-regression modelling adjusting for potential confounders. Sensitivity analyses were conducted to examine several exposure and outcome definitions. Results Patients with hypogammaglobulinaemia had longer disease duration, more lupus nephritis history, higher proteinuria and more accumulated damage. Low IgA level was associated with increased risk of clinically relevant infection [hazard ratio (HR): 2.24, 95% CI: 1.61, 3.12] while low IgG (HR: 1.15, 95% CI: 0.84, 1.59) or low IgM (HR: 0.95, 95% CI: 0.73, 1.23) was not. Low immunoglobulin recovery in the first year was 2.5% (11), second year 8.2% (36), third year 10.1% (44) and fourth year 18.4% (80), and 60% (263) of acquired hypogammaglobulinaemia recovered over 4 years. Conclusion The majority of acquired hypogammaglobulinaemia in adult patients with SLE is transient. Only low acquired IgA was associated with increased risk of infection among adult patients with SLE. Whether immunoglobulin replacement provides additional protective effect requires further investigation.

Objective In the present study, we compared the outcomes of elective abdominal aortic aneurysm (AAA) repair in patients with and without rheumatoid arthritis (RA) stratified by the type of surgery. Methods A retrospective population-based cohort study was conducted from 2003 to 2016. Linked administrative health data from Ontario, Canada were used to identify all patients aged ≥65 years who had undergone elective open or endovascular AAA repair during the study period. Patients were identified using validated procedure and billing codes and matching using propensity scores. The primary outcome was survival. The secondary outcomes were major adverse cardiovascular events (MACE)-free survival (defined as freedom from death, myocardial infarction, and stroke), reintervention, and secondary rupture. Results Of 14,816 patients undergoing elective AAA repair, a diagnosis of RA was present for 309 (2.0%). The propensity-matched cohort included 234 pairs of RA and control patients. The matched cohort was followed up for a mean ± standard deviation of 4.93 ± 3.35 years, and the median survival was 6.76 and 7.31 years for the RA and control groups, respectively. Cox regression analysis demonstrated no statistically significant differences in the hazards for death, MACE, reintervention, or secondary rupture. Analysis of the differences in outcomes stratified by repair approach also showed no statistically significant differences in the hazards for death, MACE, reintervention, or secondary rupture. Conclusions We found no statistically significant differences in survival, MACE, reintervention, or secondary rupture among patients with RA undergoing elective AAA repair compared with controls. Further studies are required to evaluate the impact of comorbidities and antirheumatic medications on the outcomes of elective AAA repair.

As the Middle East respiratory syndrome coronavirus (MERS-CoV) continues to occur in small outbreaks in Saudi Arabia, we aimed to assess the knowledge, attitudes and intended practices of healthcare workers (HCWs) during the early stage of the COVID-19 pandemic and compare worry levels with previous findings during the MERS-CoV outbreak in 2015. We sent an adapted version of our previously published MERS-CoV questionnaire to the same cohort of HCWs at a tertiary hospital in Saudi Arabia. About 40% of our sample had previous experience with confirmed or suspected MERS-CoV patients, and those had a significantly higher knowledge score (13.16 ± 2.02 vs. 12.58 ± 2.27, P = 0.002) and higher adherence to protective hygienic practices (2.95 ± 0.80 vs. 2.74 ± 0.92, P = 0.003). The knowledge scores on COVID-19 were higher in the current cohort than the previous MERS-CoV outbreak cohort (68% vs. 79.7%, P < 0.001). HCWs from the current cohort who felt greater anxiety from COVID-19 compared to MERS-CoV were less likely to have been exposed to MERS-CoV infected/suspected cases (odds ratio (OR) = 0.646, P = 0.042) and were less likely to have attended the hospital awareness campaign on COVID-19 (OR = 0.654, P = 0.035). We concluded that previous experience with MERS-CoV was associated with increased knowledge and adherence to protective hygienic practices, and reduction of anxiety towards COVID-19.

IntroductionCoronavirus disease 2019 (COVID-19) has caused an unprecedented health crisis around the world, not least because of its heterogeneous clinical presentation and course. The new information on the pandemic emerging daily has made it challenging for healthcare workers (HCWs) to stay current with the latest knowledge, which could influence their attitudes and practices during patient care.MethodsThis study is a follow-up evaluation of changes in HCWs’ knowledge, attitudes, and practices as well as anxiety levels regarding COVID-19 since the beginning of the pandemic. Data were collected through an anonymous, predesigned, self-administered questionnaire that was sent online to HCWs in Saudi Arabia.ResultsThe questionnaire was sent to 1500 HCWs, with a 63.8% response rate (N=957). The majority of respondents were female (83%), and the most common age group was 31–40 years (52.2%). Nurses constituted 86.3% of the respondents. HCWs reported higher anxiety during the COVID-19 pandemic which increased from 4.91±2.84 to 8.6±2.27 on an 11-point Likert scale compared to other viral outbreaks. HCWs believed that their own preparedness as well as that of their hospital’s intensive care unit (ICU) or emergency room (ER) was higher during the COVID-19 pandemic than during the Middle East respiratory syndrome coronavirus pandemic (2012–2015). About 58% of HCWs attended one or more simulations concerning the management of COVID-19 patients in their ICU/ER, and nearly all had undergone N95 mask fit testing. The mean score of HCWs’ knowledge of COVID-19 was 9.89/12. For most respondents (94.6%), the perception of being at increased risk of infection was the main cause of anxiety related to COVID-19; the mean score of anxiety over COVID-19 increased from 4.91±2.84 before to 8.6±2.27 during the pandemic in Saudi Arabia.ConclusionsHCWs’ anxiety levels regarding COVID-19 have increased since a pandemic was declared. It is vital that healthcare facilities provide more emotional and psychological support for all HCWs.

Objective Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin in which interleukin (IL) 17 has been genetically and therapeutically recognised as a key player. Identification of the cellular sources and inducers of IL-17 is crucial in our understanding of the drivers of inflammation in AS. Recently, mucosal-associated invariant T (MAIT) cells have been implicated in autoimmune diseases. Their gut origin, effector phenotype and expression of multiple AS-associated genes, such as IL7R and IL23R , makes them potential contributors to the pathogenesis of AS. Methods Mononuclear cells from patients with AS, healthy controls (HCs) and patients with rheumatoid arthritis were isolated from blood and synovial fluid (SF). Flow cytometry was used to identify MAIT cells. Phenotype was assessed by intracellular staining for cytokines and granzyme. Function was assessed by antigen-specific stimulation using Salmonella , or antigen non-specific activation via priming with IL-7 or IL-23. Results MAIT cells were reduced in frequency in the blood of patients with AS compared with HCs, yet patients with AS had an elevated frequency IL-17A+ MAIT cells. There was an enrichment of MAIT cells in SF, which had an exaggerated IL-17 phenotype. IL-17 elevation in AS MAIT cells was dependent on priming with IL-7 but not IL-23 or antigen stimulation. The AS-associated IL7R single nucleotide polymorphism (SNP), rs11742270, had no effect on IL-7R expression or function in the experiments performed. Conclusions This study reveals a potential role for MAIT cells in patients with AS and is the first linking IL-7 to the elevated IL-17 profile in patients through the AS-associated risk gene IL7R .

Background Allergic asthma is characterized by airway inflammation in response to antigen exposure, leading to airway remodeling and lung dysfunction. Epithelial-mesenchymal transition (EMT) may play a role in airway remodeling through the acquisition of a mesenchymal phenotype in airway epithelial cells. TGF-β1 is known to promote EMT; however, other cytokines expressed in severe asthma with extensive remodeling, such as IL-22, may also contribute to this process. In this study, we evaluated the contribution of IL-22 to EMT in primary bronchial epithelial cells from healthy and asthmatic subjects. Methods Primary bronchial epithelial cells were isolated from healthy subjects, mild asthmatics and severe asthmatics (n=5 patients per group). The mRNA and protein expression of epithelial and mesenchymal cell markers and EMT-associated transcription factors was evaluated following stimulation with TGF-β1, IL-22 and TGF-β1+IL-22. Results Primary bronchial epithelial cells stimulated with TGF-β1 underwent EMT, demonstrated by decreased expression of epithelial markers (E-cadherin and MUC5AC) and increased expression of mesenchymal markers (N-cadherin and vimentin) and EMT-associated transcription factors. IL-22 alone had no effect on epithelial or mesenchymal gene expression. However, IL-22+TGF-β1 promoted the expression of some EMT transcription factors (Snail1 and Zeb1) and led to a more profound cadherin shift, but only in cells obtained from severe asthmatics. Conclusion The impact of IL-22 on airway epithelial cells depends on the cytokine milieu and the clinical phenotype of the patient. Further studies are required to determine the molecular mechanism of IL-22 and TGF-β1 cooperativity in driving EMT in primary human bronchial epithelial cells.