Uncovering the Underworld of Axial Spondyloarthritis

Abstract

Axial spondyloarthritis (axial-SpA) is a multifactorial disease characterized by inflammation in sacroiliac joints and spine, bone reabsorption, and aberrant bone deposition, which may lead to ankylosis. Disease pathogenesis depends on genetic, immunological, mechanical, and bioenvironmental factors. HLA-B27 represents the most important genetic factor, although the disease may also develop in its absence. This MHC class I molecule has been deeply studied from a molecular point of view. Different theories, including the arthritogenic peptide, the unfolded protein response, and HLA-B27 homodimers formation, have been proposed to explain its role. From an immunological point of view, a complex interplay between the innate and adaptive immune system is involved in disease onset. Unlike other systemic autoimmune diseases, the innate immune system in axial-SpA has a crucial role marked by abnormal activity of innate immune cells, including γδ T cells, type 3 innate lymphoid cells, neutrophils, and mucosal-associated invariant T cells, at tissue-specific sites prone to the disease. On the other hand, a T cell adaptive response would seem involved in axial-SpA pathogenesis as emphasized by several studies focusing on TCR low clonal heterogeneity and clonal expansions as well as an interindividual sharing of CD4/8 T cell receptors. As a result of this immune dysregulation, several proinflammatory molecules are produced following the activation of tangled intracellular pathways involved in pathomechanisms of axial-SpA. This review aims to expand the current understanding of axial-SpA pathogenesis, pointing out novel molecular mechanisms leading to disease development and to further investigate potential therapeutic targets.

Effectiveness and safety of BCD180, anti-TRBV9⁺ T-lymphocytes monoclonal antibody in patients with active radiographic axial spondyloarthritis: 36-week results of double-blind randomized placebo-controlled phase II clinical study ELEFTA

“…Таким образом, разработка новых терапевтических опций является востребованной и перспективной задачей ревматологии, при этом в ходе поиска новых мишеней для воздействия важно учесть особенности иммунопатогенеза аксСпА. В развитии акс-СпА значимую роль играет генетическая предрасположенность, в частности доказана связь риска развития с аллелем человеческого лейкоцитарного антигена HLA-B27 главного комплекса гистосовместимости I класса (MHC-I, major histocompatibility complex) [8,9]. Инициальную роль в иммунопатогенезе аксСпА играет аномальная активность Т-клеточного звена [3,8].…”

“…Evgeny l. nasonov 1,2 , vadim i. mazurov 3 , alexander m. lila 1,4 , tatiana v. dubinina 1 , inna z. gaydukova 3,5 , svetlana a. lapshina 6,7 , alesya a. klimenko 8,9 , dmitrii v. somov 9 , sergey a. lukianov 9 , dmitry m. chudakov 9 , ivan v. zvyagin 9 , olga v. Britanova 9 , maxim a. korolev 10 , diana g. krechikova 11 , alexander a. kastanayan 12 , larisa v. Eliseeva 13 , Ruzana R. samigullina 2 , tatyana v. povarova 14 , olga v. antipova 15 , svetlana a. smakotina 16,17 , valentina n. soboleva 18 , olga B. nesmeyanova 19 , tatiana v. plaksina 20 , diana i. abdulganieva 6,7 , nikolay f. soroka 21 , irina B. vinogradova 22 , andrey p. Rebrov 23 , tatiana v. kropotina 24 , alexey l. maslyanskiy 25 , arina v. zinkinaorikhan 26 , yulia n. lin'kova 26 , polina s. pukhtinskaia 26 , maria a. morozova 26 , galina a. vinderskaya 26 the aim -to evaluate the clinical effectiveness, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of seniprutug (BCD-180) in patients with radiographic active axial spondyloarthritis (r-axSpA, or ankylosing spondylitis). subjects and methods.…”

Beyond the horizon: Innovations and future directions in axial-spondyloarthritis

“…Axial spondyloarthritis results from multiple interacting factors including genetic risks, immune dysregulation, biomechanics, and environmental triggers. [ 22 ] While PsA is traditionally considered an enthesitis-driven disease,[ 23 ] in axSpA several evidence indicates bone marrow inflammation is a central early event. [ 24 , 25 ] Thus, MRI reveals that BME and osteitis frequently precede clinical and radiological enthesitis.…”

“…In this regard, the pleiotropic cytokine granulocyte macrophagecolony stimulating factor (GM-CSF) promotes multiple inflammatory and osteoproliferative processes in axSpA pathogenesis, hence it has been considered a possible therapeutic target. [ 22 ] However, phase II results for the GM-CSF inhibitor namilumab were disappointing (NCT03622658). This highlights the ongoing challenge of effectively targeting a single cytokine in a multifactorial disease.…”

Advances in Molecular Medicine: Unravelling Disease Complexity and Pioneering Precision Healthcare

“…The next four reviews deal with diverse inflammatory conditions. Axial spondyloarthritis (axial-SpA) is a multifactorial disease affecting the sacroiliac joints and spine, leading to inflammation, bone reabsorption, and ankylosis, and its pathogenesis is not yet fully understood [ 9 ]. The disease pathogenesis involves genetic, immunological, mechanical, and environmental factors, with HLA-B27 being a significant genetic factor.…”