Article

Ectopic lymphoid neogenesis in psoriatic arthritis

Servicio de Reumatología, Hospital 12 de Octubre, 28041 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

ABSTRACT 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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    ABSTRACT: The therapeutic benefit of depleting B cells in rheumatoid arthritis (RA) has refocused attention on B cells with increasing awareness on their role in autoimmunity and their function beyond autoantibody production. The rapid increase in our comprehension of B-cell pathobiology is progressively opening novel perspectives in the area of B cell-targeted therapies with the expectation to define more specific approaches able to preserve the homeostasis of the humoral response while disrupting the pathogenic components. In parallel, B-cell activity in RA is starting to be explored in its clinical value, in search of novel biomarkers embedded in the pathogenic process that could help classifying the disease and predicting its heterogeneous outcome beyond inflammation dynamics. In this review, we summarize current knowledge on the multiple roles that B cells play in several aspects of RA. We also analyze their distribution and potential function in different anatomic compartments with specific reference to the main sites in which the disease may be sustained and exert its detrimental effects: the systemic circulation, synovium, bone marrow, and draining lymph nodes. We also highlight novel data encouraging further research in the field of biomarkers related to B cells and their regulatory factors.
    04/2014; 2014(6):1-14. DOI:10.1155/2014/681678
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    • "While classical SLO are encapsulated structures that develop in predictable locations as a consequence of normal immune system development, under pathologic conditions, ectopic lymphoid tissues (aka TLO) may develop in peripheral tissue sites of chronic inflammation (13, 26). TLO formation has been reported within inflamed organs of patients with rheumatoid arthritis (27–29), psoriatic arthritis (30), diabetes mellitus (31–33), autoimmune gastritis [AIG; Ref. (32)], juvenile dermatomyositis (34), and Sjögren’s syndrome (35), among others. TLO formation has also been identified in the lungs of influenza virus-infected mice (36), the livers of hepatitis C virus (HCV)-infected patients (37) and in the stomachs of patients infected with Helicobacter pylori (38). "
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    ABSTRACT: Ectopic lymphoid tissue, also known as tertiary lymphoid organs (TLO) develop adaptively within sites of chronic tissue inflammation, thereby allowing the host to efficiently crossprime specific immune effector cells within sites of disease. Recent evidence suggests that the presence of TLO in the tumor microenvironment (TME) predicts better overall survival. We will discuss the relevance of extranodal T cell priming within the TME as a means to effectively promote anti-tumor immunity and the strategic use of dendritic cell (DC)-based therapies to reinforce this clinically preferred process in the cancer-bearing host.
    Frontiers in Immunology 11/2013; 4:388. DOI:10.3389/fimmu.2013.00388
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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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    ABSTRACT: Comparative data on synovial cell infiltrate and cytokine levels in anti citrullinated peptide/protein antibody (ACPA)-positive and ACPA negative rheumatoid arthritis (RA) patients are scarce. Our aim was to analyze synovial cell infiltrate and synovial fluid (SF) levels of cytokines in patients with RA according to the presence or absence of ACPA in serum. A cross-sectional study in a single center including consecutive RA patients was performed. Patients were defined as 'ACPA negative' if serum was negative to two different ACPAs [second generation commercial anti-cyclic citrullinated peptide antibodies (CCP2) and chimeric fibrin/filaggrin citrullinated antibodies]. Parallel synovial tissue (ST) biopsies and SF were obtained by knee arthroscopy. Synovial cell infiltrate and endothelial cells were analyzed by immunohistochemistry and SF levels of Th1, Th2, Th17 and pro-inflammatory cytokines by Quantibody(R) Human Array. A total of 83 patients underwent arthroscopy, with a mean age of 55.9 ± 12 years, and mean disease duration of 45 months (interquartile range, IQR 10.8 to 122). 62% were female and 77% were ACPA positive. No significant differences were found in clinical variables, acute phase reactants, synovial cell infiltrate or lymphoid neogenesis (LN) between ACPA positive and negative patients. However ACPA positive patients had significantly higher levels of IL-1β, IL-10, IL-17 F and CC chemokine ligand 20 (CCL-20) than ACPA negative patients. In our cohort of patients with RA no significant differences were found in synovial cell infiltrate or synovial LN according to ACPA status. However, ACPA positive patients had higher levels of T-cell derived and pro-inflammatory cytokines than ACPA negative patients. As systemic and local inflammation was similar in the two groups, these findings support a distinct synovial physiopathology.
    Arthritis research & therapy 11/2013; 15(6):R182. DOI:10.1186/ar4372 · 3.75 Impact Factor
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