Spondyloarthritis (SpA)*:
An inflammatory pathway different from RA

*Specifically, psoriatic arthritis (PsA) and ankylosing spondylitis (AS).

Recent investigations have revealed distinctions in the T cell subtypes associated with the pathogenesis of SpA and RA1

The presence of serum rheumatoid factor (RF) and spontaneous RF-secreting B cells is a common feature in most patients with RA.2,3

In contrast, most patients with PsA and AS are RF-negative. Many AS patients in particular are positive for HLA-B27, which is thought to facilitate the role of T cells in the pathogenesis of SpA.4,5

T cells contribute to both the inflammatory and osteoproliferative processes characteristic of SpA. IL-17A-expressing T cell levels are elevated in the bone marrow and synovial fluid of joints in patients with PsA and AS.5-8 Studies have shown blood levels of Th-17 and IL-17+/CD- cells are higher in patients with PsA and AS than in patients with RA.1,7

With SpA, an initial, as yet unknown, trigger activates cells to express cytokines, promoting chronic inflammation and bone erosion and formation.9-11

The pathophysiology of SpA is complex and involves the interplay between multiple cell types and cytokines, including dendritic cells, T cells, TNF-α, IL-6, IL-23, IL-17A, and IL-22.8-10

Reality of SpA

Take a closer look at the reality of SpA1,6,10-22

Cells in Pathogenesis of SpA Cells in Pathogenesis of SpA
  • SpA Dendritic Cell

    Dendritic cell

    Dendritic cell Upon activation (from injury or infection), dendritic cells produce IL-23, a cytokine that mediates the differentiation of naive T cells into Th1, Th2, or Th17 cells.12-14
  • SpA IL-23

    IL-23

    IL-23 IL-23, a cytokine produced by dendritic cells, contributes to the differentiation of naive CD4+ T cells into Th17 cells, and is associated with pathologic changes to the bone and cartilage.10,12,15
  • SpA CD4 and T Lymphocytes

    CD4+ T lymphocyte

    CD4+ T lymphocyte The T cell pathway has been implicated in the pathogenesis of SpA. CD4+ T cells can differentiate into Th1, Th2, and Th17 cells, initiating an inflammatory cascade.6,7,12,16,17
  • SpA Th17 Cell

    Th17 cell

    Th17 cell Th17 cells are derived from CD4+ T cells that have been activated through antigen stimulation and through the action of specific dendritic cell-derived cytokines, such as IL-23, transforming growth factor-β, and IL-6. In turn, Th17 cells secrete several effector cytokines, including IL-17A, TNF-α, and IL-22.12,18
  • SpA IL-17A

    IL-17A

    IL-17A IL-17A is produced by Th17 cells, and by certain cells of the innate immune system, such as neutrophils and mast cells.8,12

    IL-17A has an inflammatory effect on a number of cells including macrophages, epithelial cells, osteoblasts involved in bone erosion, and chondrocytes, which damage cartilage.19

    Higher levels of IL-17A and IL-17A-producing cells were found in the joint synovial fluid of patients with PsA and AS than in patients with RA or OA.1,16,17,20
  • SpA Tumor Necrosis Factor-α

    TNF-α

    TNF-α Various cells—including T cells, macrophages, mast cells, and keratinocytes—produce TNF-α, leading to cytokine production and immune cell recruitment.21
  • SpA IL-22

    IL-22

    IL-22 IL-22 is a cytokine also produced by Th17 cells. IL-22 has been implicated in helping to drive inflammation and bone formation in SpA.10,11
  • SpA Osteoblast

    Osteoblast

    Osteoblast Bone loss and joint destruction that are characteristic of SpA diseases are mediated through osteoblast stimulation of osteoclasts.19,22
  • SpA Osteoclast

    Osteoclast

    Osteoclast T-cell mediated secretion of inflammatory cytokines supports the activation of osteoclasts that can lead to bone loss.18
  • SpA Chondrocyte

    Chondrocyte

    Chondrocyte Inflammatory activity disrupts matrix production in chondrocytes and leads to eventual cartilage damage.5,19,23
  • SpA Keratinocyte

    Keratinocyte

    Keratinocyte Chronic disruptions in the inflammatory signaling responsible for keratinocyte production are thought to underlie skin and joint changes characteristic of psoriatic disease.21

Discover the SpA Burden Right Arrow Image

IL=interleukin; OA=osteoarthritis; RA=rheumatoid arthritis; Th=T helper cells; TNF=tumor necrosis factor.

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