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Objective: The objective is to characterize transcriptomic profiles and immune cell composition and distribution in juvenile idiopathic arthritis (JIA) synovial biopsies, assess for associations of these features with clinical parameters, and compare JIA and rheumatoid arthritis (RA) synovial features., Methods: RNA sequencing (RNASeq) was performed on 24 samples, with pathway analysis and inference of relative abundance of immune cell subsets based on gene expression data. Two multiplex fluorescence immunohistochemistry (IHC) panels were performed on 28 samples (including 13 on which RNASeq was performed), staining for CD206 - classical and CD206 + nonclassical macrophages, and CD8 + and CD4 + T and B lymphocytes. Data were compared to a published series of early RA synovial biopsies., Results: Pathway analysis of the most variably expressed genes (n = 339) identified a B and plasma cell signature as the main driver of heterogeneity in JIA synovia, with strong overlap between JIA and RA synovitis. Multiplex IHC confirmed heterogeneity of immune cell infiltration. M1-like macrophage-rich synovial lining was associated with greater lining hypertrophy and higher (CD45 + ) pan-immune cell and CD8 + T cell infiltration., Conclusion: Our study indicates significant similarities between JIA and RA synovitis. Similar to RA, JIA synovia may be broadly categorized into two groups: (1) those with an inflammatory/adaptive immune transcriptomic signature, M1-like macrophage and CD8 + T cell infiltration, and thicker, M1-like macrophage-rich synovial lining, and (2) those with an M2-like macrophage transcriptomic signature, greater M2/M1-like macrophage ratios, and thinner, M2-like macrophage-rich synovial lining. Synovial features were not significantly associated with clinical parameters, likely because of group size and heterogeneity., (© 2024 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: Tumor necrosis factor (TNF) drives bone destruction, but it also inhibits new bone formation by inducing Dkk-1, an inhibitor of the Wnt pathway. Accordingly, blocking of Dkk-1 reverses the phenotype in experimental arthritis from a pattern of bone destruction to a pattern of bone formation. To delineate the potential role of Dkk-1 in the structural phenotype of human arthritis, we analyzed the expression of Dkk-1 and its regulation by proinflammatory cytokines in the inflamed peripheral joints of patients with spondyloarthritis (SpA) and rheumatoid arthritis (RA)., Methods: Expression of Dkk-1 and proinflammatory cytokines was determined by enzyme-linked immunosorbent assay and microarray analysis in synovial fluid (SF) and synovial tissue, respectively. Regulation of Dkk-1 production by proinflammatory cytokines was assessed in fibroblast-like synoviocyte (FLS) cultures., Results: TNF and interleukin-1β (IL-1β) levels, were higher in RA SF than in SpA SF (P < 0.001 for both), whereas levels of IL-6 were not. Levels of Dkk-1 were similar in SpA SF and RA SF and were not correlated with TNF and IL-1β levels. However, Dkk-1 levels showed an inverse correlation with IL-6 levels in both SpA SF (r = -0.31, P = 0.04) and RA SF (r = -0.39, P = 0.01); this result was reproduced at the messenger RNA level in synovial tissue. In vitro experiments with FLS confirmed that Dkk-1 production was strongly induced by TNF but clearly suppressed by IL-6. Moreover, IL-6 was able to suppress the TNF-induced up-regulation of Dkk-1 production by FLS., Conclusion: The inverse correlation of Dkk-1 levels with IL-6 levels observed in vivo in the inflamed joints was mirrored by the differential regulation of Dkk-1 production by TNF and IL-6 in vitro. The relative balance between these and other factors in the arthritic joints may determine functional Wnt signaling and tissue remodeling., (© 2015, American College of Rheumatology.)

Objective: To describe Group B Streptococcus (GBS) prevention policies at 12 Latin American sites participating in the NICHD (Eunice Kennedy Shriver National Institute of Child Health and Human Development) International Site Development Initiative (NISDI) Longitudinal Study in Latin American Countries (LILAC) and to determine rates of rectovaginal colonization and GBS-related disease among HIV-infected pregnant women and their infants., Methods: Site surveys were used to assess prevention policies and practices administered cross-sectionally during 2010. Data collected in NISDI from 2008 to 2010 regarding HIV-infected pregnant women were used to determine rates of colonization and GBS-related disease., Results: Of the 9 sites with a GBS prevention policy, 7 performed routine rectovaginal screening for GBS. Of the 401 women included in the NISDI study, 56.9% were at sites that screened. The GBS colonization rate was 8.3% (19/228 women; 95% confidence interval [CI], 5.1%-12.7%). Disease related to GBS occurred in 0.5% of the participants (2/401 women; 95% CI, 0.1%-1.8%); however, no GBS-related disease was reported among the 398 infants (95% CI, 0.0%-0.9%)., Conclusion: Improved efforts to implement prevention policies and continued surveillance for GBS are needed to understand the impact of GBS among HIV-infected pregnant women and their infants in Latin America., (Copyright © 2012 International Federation of Gynecology and Obstetrics. All rights reserved.)