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Role of MicroRNAs in Inflammatory Joint Diseases: A Review

Syed NH, Mussa A, Elmi AH, Jamal Al-Khreisat M, Ahmad Mohd Zain MR, Nurul AA

Immunol Invest, 2024 Feb;53(2):185-209.
PMID: 38095847 DOI: 10.1080/08820139.2023.2293095

Inflammatory arthritis commonly initiates in the soft tissues lining the joint. This lining swells, as do the cells in it and inside the joint fluid, producing chemicals that induce inflammation signs such as heat, redness, and swelling. MicroRNA (miRNA), a subset of non-coding small RNA molecules, post-transcriptionally controls gene expression by targeting their messenger RNA. MiRNAs modulate approximately 1/3 of the human genome with their multiple targets. Recently, they have been extensively studied as key modulators of the innate and adaptive immune systems in diseases such as allergic disorders, types of cancer, and cardiovascular diseases. However, research on the different inflammatory joint diseases, such as rheumatoid arthritis, gout, Lyme disease, ankylosing spondylitis, and psoriatic arthritis, remains in its infancy. This review presents a deeper understanding of miRNA biogenesis and the functions of miRNAs in modulating the immune and inflammatory responses in the above-mentioned inflammatory joint diseases. According to the literature, it has been demonstrated that the development of inflammatory joint disorders is closely related to different miRNAs and their specific regulatory mechanisms. Furthermore, they may present as possible prognostic and diagnostic biomarkers for all diseases and may help in developing a therapeutic response. However, further studies are needed to determine whether manipulating miRNAs can influence the development and progression of inflammatory joint disorders.

Matched MeSH terms: Spondylitis, Ankylosing*
Antagonizing IL-6 in ankylosing spondylitis: a short review

Rajalingham S, Das S

Inflamm Allergy Drug Targets, 2012 Aug 1;11(4):262-5.
PMID: 22452603

Ankylosing spondylitis (AS) is a chronic inflammatory disorder with predilection for the axial skeleton, leading to progressive restricted mobility and deformity of the spine. The fundamental mechanism involves autoimmunity orchestrated by T cells. Similar to other rheumatic diseases, the complex interplay of cytokines such as tumour necrosis factor alpha, interleukin-6 (IL 6) and interleukin-10 (IL 10) has been implicated in the pathogenesis of the disease. Despite extensive research over the past decades, the treatment options for AS, are limited. Non steroidal antiinflammatory drugs are the first line of therapy, whereas anti TNF drugs are administered for refractory cases which fail to respond to the treatment. There have been conflicting views on the correlation of IL 6 with disease activity in AS. As such, the debate on the role of anti IL6 in AS is still ongoing. Anti IL 6 such as tocilizumab and siltuximab have proven efficacy based on the large randomized controlled trials. The Food and Drug Administration (FDA) has approved these drugs for treating rheumatoid arthritis and systemic juvenile idiopathic arthritis. Researchers have adventurously experimented anti IL 6 therapy in AS but the conclusions made were not consolidated into international guidelines or consensus statement for clinical practice. In the present review, we explore the role of anti IL6 in the treatment of AS based on the cumulative evidence over recent years.

Matched MeSH terms: Spondylitis, Ankylosing/drug therapy*; Spondylitis, Ankylosing/immunology
A novel HLA-B*27 allele, B*27:138, identified by sequence-based typing

Koay BT, Norfarhana KF, Norhafizi MY, Lee YY, Dhaliwal JS

Tissue Antigens, 2015 Aug;86(2):143-4.
PMID: 26105122 DOI: 10.1111/tan.12599

Ankylosing spondylitis (AS) is a chronic inflammatory disorder with predilection for the axial skeleton, leading to progressive restricted mobility and deformity of the spine. The fundamental mechanism involves autoimmunity orchestrated by T cells. Similar to other rheumatic diseases, the complex interplay of cytokines such as tumour necrosis factor alpha, interleukin-6 (IL 6) and interleukin-10 (IL 10) has been implicated in the pathogenesis of the disease. Despite extensive research over the past decades, the treatment options for AS, are limited. Non steroidal antiinflammatory drugs are the first line of therapy, whereas anti TNF drugs are administered for refractory cases which fail to respond to the treatment. There have been conflicting views on the correlation of IL 6 with disease activity in AS. As such, the debate on the role of anti IL6 in AS is still ongoing. Anti IL 6 such as tocilizumab and siltuximab have proven efficacy based on the large randomized controlled trials. The Food and Drug Administration (FDA) has approved these drugs for treating rheumatoid arthritis and systemic juvenile idiopathic arthritis. Researchers have adventurously experimented anti IL 6 therapy in AS but the conclusions made were not consolidated into international guidelines or consensus statement for clinical practice. In the present review, we explore the role of anti IL6 in the treatment of AS based on the cumulative evidence over recent years.

Matched MeSH terms: Spondylitis, Ankylosing/diagnosis; Spondylitis, Ankylosing/genetics*
Ankylosing spondylitis in Singapore: a study of 150 patients and a local update

Koh WH, Boey ML

Ann Acad Med Singap, 1998 Jan;27(1):3-6.
PMID: 9588266

This paper presents the results of a clinical study of 150 patients in Singapore with ankylosing spondylitis (AS) and reviews recent developments locally with regards to the disease. The patients were predominantly males (ratio 7:1) and Chinese (n = 147). The onset of disease is usually in the early twenties and there was a mean delay of 6.3 years before diagnosis was made. Peripheral joint involvement is common but apart from uveitis (17%), extra-articular manifestations are rare. AS patients have abnormal lipid profiles and lower bone mineral density compared to healthy controls. HLA*B2704 is the predominant subtype in our Chinese patients whilst HLA*B2706 was found only in healthy controls. Intensive group physiotherapy is beneficial for patients with spondyloarthropathy.

Matched MeSH terms: Spondylitis, Ankylosing/diagnosis; Spondylitis, Ankylosing/drug therapy; Spondylitis, Ankylosing/epidemiology*
Fulltext Fracture-dislocation at C6-C7 level with quadriplegia after traditional massage in a patient with ankylosing spondylitis: a case report

Abilash K, Mohd Q, Ahmad Z, Towil B

Malays Orthop J, 2017 Jul;11(2):75-77.
PMID: 29021885 MyJurnal DOI: 10.5704/MOJ.1707.013

Ankylosing spinal disorders (ASD) tend to result in fractures and/or dislocations after minor trauma because of the altered biomechanical properties. The relative risk of traumatic vertebral fractures in patients with ankylosing spondylitis has been estimated as three times higher than in the general population. These spine traumas, which are located at cervical level in 81% of patients with ankylosing spondylitis, are complicated by neurological lesions in 65% of patients, due to the high inherent instability of these fractures. Traditional massage is an ancient practice in many parts of Asia. It has many benefits that are currently recognized world-wide. However, it can be dangerous and even lethal if practised without adequate knowledge and skill. We report a case of C6-C7 fracture-dislocation with complete neurology and neurogenic shock in a middle aged man with undiagnosed ankylosing spondylitis.

Matched MeSH terms: Spondylitis, Ankylosing
Atypical case of diffuse idiopathic skeletal hyperostosis mimicking ankylosing spondylitis in a young woman with polycystic ovary syndrome

Ong SG, Ding HJ

Med J Malaysia, 2019 12;74(6):558-560.
PMID: 31929491

Both diffuse idiopathic skeletal hyperostosis and ankylosing spondylitis present with similar clinical manifestations of restricted spinal mobility and postural abnormalities, and radiographic resemblances including axial spine involvement and enthesopathy. Nonetheless, they are two entirely different diseases. We report an unusual case of DISH in a young woman whose diagnosis was established based on radiologic features. This case report aims to highlight the under-recognised radiologic aspects of the differential diagnosis between DISH and AS in order to avoid an inaccurate diagnosis.

Matched MeSH terms: Spondylitis, Ankylosing/diagnosis*
Fulltext Cervical spine fracture in a patient with ankylosing spondylitis causing a C2-T9 spinal epidural hematoma- Treatment resulted in a rapid and complete recovery from tetraplegia: Case report and literature review

Wong AS, Yu DH

Asian J Neurosurg, 2015 3 15;10(1):53.
PMID: 25767586 DOI: 10.4103/1793-5482.151519

Full recovery from tetraplegia is uncommon in cervical spine injury. This has not being reported for cervical spine fracture in a patient with ankylosing spondylitis causing spinal epidural hematoma. We report on a case of cervical spine fracture in a patient with ankylosing spondylitis who came with tetraplegia. He underwent a two stage fixation and fusion. He had a complete recovery. Two hours after the operation he regained full strength in all the limbs while in the Intensive Care Unit. He went back to full employment. There are only two other reports in the literature where patients with ankylosing spondylitis and extradural hematoma who underwent treatment within 12 h and recovered completely from tetraparesis and paraplegia respectively. Patient with ankylosing spondylitis has a higher incidence of spinal fracture and extradural hematoma. Good outcome can be achieved by early diagnosis and treatment. This can ensure not only a stable spine, but also a rapid and complete recovery in a tetraplegic patient.

Matched MeSH terms: Spondylitis, Ankylosing
Acute uveitic glaucoma in ankylosing spondylitis

Ee CL, Sockalingam S, Kamalden TA

Postgrad Med J, 2018 Jul;94(1113):417.
PMID: 29907697 DOI: 10.1136/postgradmedj-2018-135560
Matched MeSH terms: Spondylitis, Ankylosing/complications*
Fulltext Minimally Invasive versus Conventional Open Surgery for Fixation of Spinal Fracture in Ankylosed Spine

Chung WH, Ng WL, Chiu CK, Chan C, Kwan MK

Malays Orthop J, 2020 Nov;14(3):22-31.
PMID: 33403059 DOI: 10.5704/MOJ.2011.005

Introduction: This was a retrospective study aimed to investigate the perioperative outcomes of long construct minimally invasive spinal stabilisation (MISt) using percutaneous pedicle screws (PPS) versus conventional open spinal surgery in the treatment of spinal fracture in ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH).
Material and Methods: Twenty-one patients with AS and DISH who were surgically treated between 2009 and 2017 were recruited. Outcomes of interest included operative time, intra-operative blood loss, complications, duration of hospital stay and fracture union rate.
Results: Mean age was 69.2 ± 9.9 years. Seven patients had AS and 14 patients had DISH. 17 patients sustained AO type B3 fracture and 4 patients had type B1 fracture. Spinal trauma among these patients mostly involved thoracic spine (61.9%), followed by lumbar (28.6%) and cervical spine (9.5%). MISt using PPS was performed in 14 patients (66.7%) whereas open surgery in 7 patients (33.3%). Mean number of instrumentation level was 7.9 ± 1.6. Mean operative time in MISt and open group was 179.3 ± 42.3 minutes and 253.6 ± 98.7 minutes, respectively (p=0.028). Mean intra-operative blood loss in MISt and open group was 185.7 ± 86.4ml and 885.7 ± 338.8ml, respectively (p<0.001). Complications and union rate were comparable between both groups.
Conclusion: MISt using PPS lowers the operative time and reduces intra-operative blood loss in vertebral fractures in ankylosed disorders. However, it does not reduce the perioperative complication rate due to the premorbid status of the patients. There was no significant difference in the union rate between MISt and open surgery.

Matched MeSH terms: Spondylitis, Ankylosing
Fulltext Optimization of Aceclofenac Proniosomes by Using Different Carriers, Part 1: Development and Characterization

Sammour RMF, Taher M, Chatterjee B, Shahiwala A, Mahmood S

Pharmaceutics, 2019 Jul 18;11(7).
PMID: 31323799 DOI: 10.3390/pharmaceutics11070350

In the contemporary medical model world, the proniosomal system has been serving as a new drug delivery system that is considered to significantly enhance the bioavailability of drugs with low water solubility. The application of this system can improve the bioavailability of aceclofenac that is used for the relief of pain and inflammation in osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. The present study is intended to develop an optimized proniosomal aceclofenac formula by the use of different carriers. Aceclofenac proniosomes have been prepared by slurry method, and different carriers such as maltodextrin, mannitol, and glucose were tried. Prepared proniosomes characterized by differential scanning calorimetry (DSC) analysis and Fourier transform infrared (FTIR) analysis revealed the compatibility of the drug chosen with the ingredient added, powder X-ray diffractometry (XRD) confirmed the amorphous phase of the prepared proniosomes, and finally, the surfactant layer was observed by scanning electron microscopy (SEM). Aceclofenac physical state transformations were confirmed with all formulas but maltodextrin proniosomes exhibited solubility more than other formulations. HPLC method has been used to analyze the niosomes derived from proniosomes in terms of their entrapment capability and drug content. The obtained results revealed that aceclofenac proniosomes can be successfully prepared by using different carriers.

Matched MeSH terms: Spondylitis, Ankylosing