Significance of IL-7 and IL-7R in RA and autoimmunity.

While physiological levels of IL-7 are essential for T cell proliferation, survival and co-stimulation, its escalated concentration has been associated with autoimmune diseases such as Rheumatoid arthritis (RA). Expression of IL-7 and IL-7R in RA monocytes is linked to disease activity score and TNF transcription. TNF stimulation can modulate IL-7 secretion and IL-7R frequency in myeloid cells, however, only IL-7R transcription levels are downregulated in anti-TNF responsive patients. Elevated levels of IL-7 in RA synovial tissue and fluid are involved in attracting RA monocytes into the inflammatory joints and remodeling them into proinflammatory macrophages and mature osteoclasts. Further, IL-7 amplification of RA Th1 cell differentiation and IFNγ secretion, can directly prime myeloid IL-7R expression and thereby exacerbate IL-7-mediated joint inflammatory and erosive imprints. In parallel, IL-7 accentuates joint angiogenesis by expanding the production of proangiogenic factors from RA macrophages and endothelial cells. In preclinical models, blockade of IL-7 or IL-7R can effectively impair joint inflammation, osteoclast formation, and neovascularization primarily by impeding monocyte and endothelial cell infiltration as well as inhibition of pro-inflammatory macrophage and Th1/Th17 cell differentiation. In conclusion, disruption of IL-7/IL-7R signaling can uniquely intercept the crosstalk between RA myeloid and lymphoid cells in their ability to trigger neovascularization.

Synovial Fluid Cytokines, Chemokines and MMP Levels in Osteoarthritis Patients with Knee Pain Display a Profile Similar to Many Rheumatoid Arthritis Patients.

BACKGROUND: There are currently no effective disease-modifying drugs to prevent cartilage loss in osteoarthritis and synovial fluid is a potentially valuable source of biomarkers to understand the pathogenesis of different types of arthritis and identify drug responsiveness. The aim of this study was to compare the differences between SF cytokines and other proteins in patients with OA (n = 21) to those with RA (n = 27) and normal knees (n = 3). METHODS: SF was obtained using ultrasound (US) guidance and an external pneumatic compression device. RA patients were categorized as active (n = 20) or controlled (n = 7) based upon SF white blood cell counts (> or <300 cells/mm3). Samples were cryopreserved and analyzed by multiplex fluorescent bead assays (Luminex). Between-group differences of 16 separate biomarker proteins were identified using ANOVA on log10-transformed concentrations with p values adjusted for multiple testing. RESULTS: Only six biomarkers were significantly higher in SF from active RA compared to OA-TNF-α, IL-1-ß IL-7, MMP-1, MMP-2, and MMP-3. Only MMP-8 levels in RA patients correlated with SF WBC counts (p < 0.0001). Among OA patients, simultaneous SF IL-4, IL-6, IL-8, and IL-15 levels were higher than serum levels, whereas MMP-8, MMP-9, and IL-18 levels were higher in serum (p < 0.05). CONCLUSION: These results support the growing evidence that OA patients have a pro-inflammatory/catabolic SF environment. SF biomarker analysis using multiplex testing and US guidance may distinguish OA phenotypes and identify treatment options based upon targeted inflammatory pathways similar to patients with RA.

Sarcoidosis and autoimmunity.

PURPOSE OF REVIEW: Sarcoidosis is a poorly understood multisystem granulomatous disease that frequently involves the lungs but can affect any organ system. In this review, we summarize recent developments in the understanding of the immune dysregulation seen in sarcoidosis and propose a new expanded definition of human autoimmunity in sarcoidosis, and the implications it would have on treating sarcoidosis with targeted immunotherapy regimens in the future. RECENT FINDINGS: Sarcoidosis has been linked to infectious organisms like Mycobacterium and Cutibacterium, and certain manifestations of sarcoidosis have been linked to specific HLA alleles, but the overall pathogenesis remains uncertain. Sarcoidosis patients have similar patterns of cellular immune dysregulation seen in other autoimmune diseases like rheumatoid arthritis, and recent large-scale population studies show that sarcoidosis frequently presents with other autoimmune diseases. SUMMARY: Advancements in the understanding of sarcoidosis support its consideration as an autoimmune disease. Sarcoidosis patients carry a higher risk of comorbid autoimmune conditions which offers an excellent opportunity to further understand autoimmunity and explore biologic therapies in sarcoidosis treatment, and furthermore will better targeted immunotherapy regimens for sarcoidosis patients in the future.

Load-Power Relationships for High-Speed Knee Extension Exercise.

Chen, L, Davison, SW, Selimovic, EA, Mueller, RE, Beatty, SR, Carter, KA, Parmar, PJ, Symons, TB, Pantalos, GM, and Caruso, JF. Load-power relationships for high-speed knee extension exercise. J Strength Cond Res 33(6): 1480-1487, 2019-Seventy subjects did 4 knee extensor workouts with their left legs to assess load-power relationships produced on a high-speed trainer (HST; Newnan, GA, USA). Each workout is composed of 4 sets done on the HST at a different load (1, 4.4, 6.7, 9 kg). A Latin Squares Design determined load sequence per workout. Average power (AP) and peak power (PP) and those same values normalized to body mass (BM) and fat-free mass (AP/BM, PP/BM, AP/FFM, PP/FFM) were each analyzed with 2 (gender) × 4 (load) analysis of variances, with repeated measures for load. We assessed relationships between normalized loads and AP and PP values with correlation coefficients. Average power results revealed a significant interaction, with men > women at 9 kg. Peak power/body mass also yielded an interaction, with women > men at 6.7 and 9 kg. Average power/fat-free mass and PP/FFM each produced interactions, with women > men at 4.4, 6.7, and 9 kg. Correlation coefficients showed significant (r = 0.80-0.82) relationships between normalized loads and AP and PP values. In conclusion, the very low inertial resistance to initiate each repetition on this novel device may in part explain our PP/BM, AP/FFM, PP/FFM results, in which higher values were achieved by women. Our practical applications imply that the low inertial resistance for HST repetitions negates male size and strength advantages typically seen when power is measured.