Nature versus nurture in the spectrum of rheumatic diseases: Classification of spondyloarthritis as autoimmune or autoinflammatory

Abstract

Spondyloarthritides (SpA) include inflammatory joint diseases with various clinical phenotypes that may also include the axial skeleton and/or entheses. SpA include psoriatic arthritis, reactive arthritis, enteropathic arthritis and ankylosing spondylitis; the latter is frequently associated with extra-articular manifestations, such as uveitis, psoriasis, and inflammatory bowel disease. SpA are associated with the HLA-B27 allele and recognize T cells as key pathogenetic players. In contrast to other rheumatic diseases, SpA affect women and men equally and are not associated with detectable serum autoantibodies. In addition, but opposite to rheumatoid arthritis, SpA are responsive to treatment regimens including IL-23 or IL-17-targeting biologics, yet are virtually unresponsive to steroid treatment. Based on these differences with prototypical autoimmune diseases, such as rheumatoid arthritis or connective tissue diseases, SpA may be better classified among autoinflammatory diseases, with a predominant innate immunity involvement. This would rank SpA closer to gouty arthritis and periodic fevers in the spectrum of rheumatic diseases, as opposed to autoimmune-predominant diseases. We herein provide available literature on risk factors associated with SpA in support of this hypothesis with a specific focus on genetic and environmental factors.

Biologic therapy and spinal radiographic progression in patients with axial spondyloarthritis: A structured literature review

“…Spondyloarthritis, characterized by inflammation of the spine and peripheral joints, includes a range of diseases such as axial spondyloarthritis (axSpA), psoriatic arthritis, reactive arthritis and enteropathic arthritis. 1,2 AxSpA is a chronic inflammatory disease with a heterogeneous clinical phenotype that primarily affects the sacroiliac joints and spine. It represents a spectrum of disease, including ankylosing spondylitis (AS, also known as radiographic axSpA) and nonradiographic axial spondyloarthritis (nr-axSpA).…”

The Phenotype and Secretory Activity of Adipose-Derived Mesenchymal Stem Cells (ASCs) of Patients with Rheumatic Diseases

“…Early long-lasting anti-inflammatory therapy may slow the progression of this irreversible structural damage [4]. This disease has certain autoinflammatory features and is mediated by interactions between innate and adaptive immune cells and cytokines [4,5].…”

Immune checkpoint inhibitor–induced inflammatory arthritis as a model of autoimmune arthritis

“…SpA is generally considered clinically to be a seronegative disease, due to the paucity of RA‐associated autoantibodies and lack of success identifying prevalent and specific autoantibodies in this patient population. While this may suggest that SpA patients do not mount efficient autoreactive humoral responses or that this disease is autoinflammatory in nature, autoantibodies to β2 microglobulin, protein phosphatase magnesium‐dependent 1A (PPMA1), CD74, LL37, and others have been found in SpA, most commonly in single‐cohort studies (reviewed in Liu et al) . Antibodies to β2 microglobulin were among the first to be described and were found in 68% of ankylosing spondylitis patients in a single study, but were not specific for the disease when compared to patients with lupus or RA .…”

“…While this may suggest that SpA patients do not mount efficient autoreactive humoral responses or that this disease is autoinflammatory in nature, autoantibodies to β2 microglobulin, protein phosphatase magnesium-dependent 1A (PPMA1), CD74, LL37, and others have been found in SpA, most commonly in single-cohort studies (reviewed in Liu et al 101 ). [102][103][104] Antibodies to β2 microglobulin were among the first to be described and were found in 68% of ankylosing spondylitis patients in a single study, but were not specific for the disease when compared to patients with lupus or RA. 103 Anti-PPMA1 antibodies have also only been described in a single study, but were found to be 67% sensitive and 73% specific for SpA, compared to other forms of IA, and a decrease in the level of these antibodies was…”