Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis

159

Objective. To assess the expression of tumor necrosis factor α (TNF α), TNF β, and their receptors in synovia of patients with juvenile rheumatoid arthritis (JRA) and juvenile spondylarthropathy (JSpA), and to determine similarities with and differences from adult RA.Methods. Twenty‐eight synovial tissue samples from patients with JRA, 6 from patients with JSpA, and 6 from patients with RA, selected for the presence of inflammatory infiltrates, were analyzed for the expression of TNF α, TNF β, and their receptors (p55 and p75 TNFR), utilizing the dual approach of reverse transcriptase—polymerase chain reaction and immunohistochemistry analysis.Results. The presence of both TNF α and TNF β expression was demonstrated in most JRA and JSpA tissues, although samples from patients with pauci‐articular JRA had somewhat lesser amounts of these cytokines. TNF β expression correlated significantly with the occurrence of lymphocytic aggregates in tissues. Staining with monoclonal antibodies specific for the p55 and p75 receptors revealed that a diverse range of cell types expressed the receptors, with the most intense p55 staining on vascular endothelial cells. In the vast majority of synovial tissues, far greater numbers of cells expressed the p55 form of the receptor than the p75 form.Conclusion. JRA and JSpA synovia are characterized by the presence of TNF α, TNF β, and cells expressing TNFR. These findings provide further evidence that TNF, through autocrine/paracrine mechanisms, may amplify local inflammation, leading to joint destruction. The prominence of TNF β in the synovium in particular subgroups of JRA patients and in JSpA patients may be a distinguishing feature of these diseases.

Section: Discussionsupporting

confidence: 93%

Patterns of expression of tumor necrosis factor α, tumor necrosis factor β, and their receptors in synovia of patients with juvenile rheumatoid arthritis and juvenile spondylarthropathy

Grom

Murray

Luyrink

et al. 1996

159

“…TGF␤ might play a key role in the new bone formation characteristic of AS (1). In this regard, it was interesting to note the trend implicating a correlation of TGF␤ with the 846 epitope at baseline, because the latter biomarker is thought to reflect cartilage matrix synthesis (5,17).…”

Section: Discussionmentioning

confidence: 99%

“…To a varying degree, peripheral joint synovitis can also be a prominent feature. Previously, pathologic studies revealed the presence of T cells and macrophages and local expression of tumor necrosis factor ␣ (TNF␣) in biopsy specimens from the sacroiliac joints of patients with active AS (1). Recent studies of anti-TNF treat-ment have demonstrated its effectiveness in short-term trials (2), although the effect of these agents on longterm sequelae, including radiographic progression, has not yet been determined.…”

mentioning

confidence: 99%

Cartilage biomarkers in ankylosing spondylitis: Relationship to clinical variables and treatment response

Kim

Stone

Payne

et al. 2005

Objective. Ankylosing spondylitis (AS) is a progressive disease in which chronic inflammation can lead to extensive new bone formation throughout the spine. At present, few measures of the activity or extent of the disease are available. In this study, we sought to determine whether markers of cartilage synthesis and degradation could provide such quantitative measures.Methods. Serum samples from 23 patients receiving infliximab treatment for AS were obtained at baseline and at weeks 2, 6, 14, and 22. Conclusion. In AS, elevated serum levels of CPII and the 846 epitope may be related to biosynthetic turnover of hyaline cartilage and the intervertebral discs but may also reflect progressive bone formation as a result of endochondral ossification. The correlation of the CPII:C2C ratio with CRP suggests that the CPII: C2C ratio might prove to be a useful marker of disease activity in AS.The hallmark of ankylosing spondylitis (AS) is acute and chronic inflammation in the sacroiliac joints as well as enthesitis, defined as inflammation at the sites of ligamentous and tendinous insertions onto bone. To a varying degree, peripheral joint synovitis can also be a prominent feature. Previously, pathologic studies revealed the presence of T cells and macrophages and local expression of tumor necrosis factor ␣ (TNF␣) in biopsy specimens from the sacroiliac joints of patients with active AS (1).

“…In patients with AS, TNF concentrations are elevated in the serum (3,4) and synovial tissue (5)(6)(7). Etanercept substantially reduces disease activity in patients with spondylarthropathies, as demonstrated in a study in psoriatic arthritis (8) and a pilot study in AS (9).…”

mentioning

confidence: 92%

Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: A randomized, controlled trial

Davis

Heijde

Braun³

et al. 2003

682

376

Results. Treatment with etanercept resulted in dramatic improvement. The ASAS20 was achieved by 59% of patients in the etanercept group and by 28% of patients in the placebo group (P < 0.0001) at week 12, and by 57% and 22% of patients, respectively, at week 24 (P < 0.0001). All individual ASAS components, acutephase reactant levels, and spinal mobility measures were also significantly improved. The safety profile of etanercept was similar to that reported in studies of patients with rheumatoid arthritis or psoriatic arthritis. The only adverse events that occurred significantly more often in the etanercept group were injection-site reactions, accidental injuries, and upper respiratory tract infections.Conclusion. Etanercept is a highly effective and well tolerated treatment in patients with active AS.Ankylosing spondylitis (AS) is an inflammatory arthritis and enthesitis involving the spine and periSupported by Immunex Corporation, Seattle, Washington, a wholly owned subsidiary