Altered thymocyte development observed in EphA4-deficient mice courses with changes in both thymic epithelial and extracellular matrix organization.

Eph receptors and their ligands, Ephrins, are involved in the thymocyte-thymic epithelial cell (TEC) interactions, key for the functional maturation of both thymocytes and thymic epithelium. Several years ago, we reported that the lack of EphA4, a Eph of the subfamily A, coursed with reduced proportions of double positive (DP) thymocytes apparently due to an altered thymic epithelial stroma [Munoz et al. in J Immunol 177:804-813, 2006]. In the present study, we reevaluate the lymphoid, epithelial, and extracellular matrix (ECM) phenotype of EphA4-/- mice grouped into three categories with respect to their proportions of DP thymocytes. Our results demonstrate a profound hypocellularity, specific alterations of T cell differentiation that affected not only DP thymocytes, but also double negative and single positive T cell subsets, as well as the proportions of positively and negatively selected thymocytes. In correlation, thymic histological organization changed markedly, especially in the cortex, as well as the proportions of both Ly51+UEA-1- cortical TECs and Ly51-UEA-1+ medullary TECs. The alterations observed in the expression of ECM components (Fibronectin, Laminin, Collagen IV), integrin receptors (VLA-4, VLA-6), chemokines (CXCL12, CCL25, CCL21) and their receptors (CXCR4, CCR7, CCR9) and in vitro transwell assays on the capacity of migration of WT and mutant thymocytes suggest that the lack of EphA4 alters T-cell differentiation by presumably affecting cell adhesion between TECs and T-TEC interactions rather than by thymocyte migration.

Anti-cyclic citrullinated peptide versus anti-Sa antibodies in diagnosis of rheumatoid arthritis in an outpatient clinic for connective tissue disease and spondyloarthritis.

OBJECTIVE: . To compare the diagnostic value of anti-cyclic citrullinated peptide (anti-CCP) and anti-Sa antibodies in serum for prediction of rheumatoid arthritis (RA) in an outpatient clinic for connective tissue diseases and spondyloarthritides. METHODS: A cross-sectional study was carried out to analyze the presence or absence of anti-CCP and anti-Sa antibodies in the sera of 250 randomly selected patients. The disease distribution in the study was as follows: 87 patients had RA (34.8%); 90 (36%) had other connective tissue diseases (CTD); 50 (20%) spondyloarthritis; 19 (7.6%) polymyalgia rheumatica; and 4 (1.6%) juvenile idiopathic arthritis. RESULTS: Anti-CCP antibodies were detected in 63 patients with RA and in 9 patients with other illnesses [sensitivity 72.4%, specificity 94.4%, positive predictive value (PPV) 87.5%]. Anti-Sa antibodies were detected in 38 patients with RA and in 6 patients with other illnesses (sensitivity 43.6%, specificity 96.3%, PPV 86.3%). Anti-CCP and anti-Sa results were discordant in up to 47 of 87 RA patients. No relation between the presence of anti-Sa and higher or lower titers of anti-CCP antibodies was observed. CONCLUSION: The diagnostic value in RA is similar for both antibodies. However, the sensitivity of anti-CCP detection is higher than that of anti-Sa. Our results suggest that presence of anti-Sa antibodies in serum may be useful as a complementary assay when anti-CCP antibodies are negative and RA is suspected.