Ectopic lymphoid neogenesis in psoriatic arthritis

Hospital 12 de Octubre, Madrid, Madrid, Spain
Annals of the Rheumatic Diseases (Impact Factor: 10.38). 07/2007; 66(6):720-6. DOI: 10.1136/ard.2006.062042
Source: PubMed


Ectopic lymphoid neogenesis (LN) occurs in rheumatoid synovium, where it is thought to drive local antigen-dependent B cell development and autoantibody production. This process involves the expression of specific homing chemokines and the development of high endothelial venules (HEV).
To investigate whether these mechanisms occur in psoriatic arthritis (PsA) synovium, where autoantibodies have not been described and the organisation and function of B cells is not clear, and to analyse their clinical correlates.
Arthroscopic synovial biopsy specimens from patients with PsA before and after tumour necrosis factor alpha blockade were characterised by immunohistochemical analysis for T/B cell segregation, peripheral lymph node addressin (PNAd)-positive HEV, and the expression of CXCL13, CCL21 and CXCL12 chemokines in relation to the size of lymphoid aggregates.
Lymphoid aggregates of variable sizes were observed in 25 of 27 PsA synovial tissues. T/B cell segregation was often observed, and was correlated with the size of lymphoid aggregates. A close relationship between the presence of large and highly organised aggregates, the development of PNAd+ HEV, and the expression of CXCL13 and CCL21 was found. Large organised aggregates with all LN features were found in 13 of 27 tissues. LN in PsA synovitis was not related to the duration, pattern or severity of the disease. The synovial LN pattern remained stable over time in persistent synovitis, but a complete response to treatment was associated with a regression of the LN features.
LN occurs frequently in inflamed PsA synovial tissues. Highly organised follicles display the characteristic features of PNAd+ HEV and CXCL13 and CCL21 expression, demonstrating that the microanatomical bases for germinal centre formation are present in PsA. The regression of LN on effective treatment indicates that the pathogenic and clinical relevance of these structures in PsA merits further investigation.

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    • "In 1978, Goldenberg and Cohen [97], after histopathologic evaluation of synovial tissues obtained from 90 patients suffering from different rheumatic diseases, concluded that the presence of lymphoid follicles could be regarded as a specific feature of RA. Over the years, several investigators have revised this assumption demonstrating that most of the chronic inflammatory arthritides share common histopathologic features, including the local organization of infiltrating mononuclear cells into aggregational structures [98–100]. A recent prospective study involving 93 patients with early arthritis of <12 months duration has failed to demonstrate any diagnostic value of synovial lymphocyte aggregates evaluated by means of T-cell markers [100]. "
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    • "Furthermore, we found a slightly higher prevalence of LN in ACPA negative patients, as have other studies [32]. These results are not unexpected, because synovial LN has also been described in around 40% of patients with PsA, a disease with no specific autoantibodies [21]. Therefore, although experimental models suggest that ACPA are produced by plasma cells associated with germinal centers in RA ST [33], clinical studies have failed until now to demonstrate an association between synovial LN and the presence or absence of ACPA in serum or SF (28). "
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