About a quarter of sclerodermic patients present calcinosis. However, patients with limited form of the disease are more likely to have calcinosis than patients with diffuse form. We report a case of a 54-year-old female patient with limited cutaneous scleroderma using rituximab (RTX) to treat lung fibrosis and arthritis. Into RTX treatment, she also had a complete resolution of calcinosis in her hands. The patient reported improvement in dyspnea and synovitis after two courses of RTX (four weekly infusions 375 mg/m(2) each). After 7 months of the first infusion, the calcinosis in her fingers had a complete remission, especially the right thumb. Based on current evidences, we discuss the use of rituximab as a promising therapy to treat not only lung disease but also calcinosis in patients with scleroderma.
Measuring changes of the T cell receptor (TCR) repertoire is important to many fields of medicine. Flow cytometry is a popular technique to study the TCR repertoire, as it quickly provides insight into the TCR-Vβ usage among well-defined populations of T cells. However, the interpretation of the flow cytometric data remains difficult, and subtle TCR repertoire changes may go undetected. Here, we introduce a novel means for analyzing the flow cytometric data on TCR-Vβ usage. By applying economic statistics, we calculated the Gini-TCR skewing index from the flow cytometric TCR-Vβ analysis. The Gini-TCR skewing index, which is a direct measure of TCR-Vβ distribution among T cells, allowed us to track subtle changes of the TCR repertoire among distinct populations of T cells. Application of the Gini-TCR skewing index to the flow cytometric TCR-Vβ analysis will greatly help to gain better understanding of the TCR repertoire in health and disease.
The objective of the study was to investigate the association between IL-8 and other biomarkers of endothelial dysfunction (MCP-1, V-CAM, I-CAM) and the disease activity scores in a sample of 54 patients with ankylosing spondylitis (AS) without use of biological agents. Fifty-four AS patients without treatment with anti-TNFs agents between 18 and 80 years old, who met modified New York criteria and at the same time the axial ASAS criteria, were evaluated using an epidemiological questionnaire that included among others clinical data, BASDAI, BASFI, ASQoL, ASDAS and plasma levels of CRP, ESR, MCP-1, IL-8, ICAM-1 and VCAM-1. IL-8 varied in proportion to disease activity rates (BASDAI and ASDAS) p < 0.05, being strongly correlated with the disease activity. The levels of adhesion molecules I-CAM and VCAM, as described in other studies, were positively correlated with predisposing factors for cardiovascular disease. IL-8 has shown to be strongly correlated with clinical markers of disease activity and inflammatory activity and may be an additional variable to the overall assessment of the activity of the AS.
Insight into the maintenance of naive T cells is essential to understand defective immune responses in the context of aging and other immune compromised states. In humans, naive CD4+ T cells, in contrast to CD8+ T cells, are remarkably well retained with aging. Here, we show that low-affinity TCR engagement is the main driving force behind the emergence and accumulation of naive-like CD4+ T cells with enhanced sensitivity to IL-2 in aged humans. In vitro, we show that these CD45RA+CD25dimCD4+ T cells can develop from conventional naive CD25−CD4+ T cells upon CD3 cross-linking alone, in the absence of costimulation, rather than via stimulation by the homeostatic cytokines IL-2, IL-7, or IL-15. In vivo, TCR engagement likely occurs in secondary lymphoid organs as these cells were detected in lymph nodes and spleen where they showed signs of recent activation. CD45RA+CD25dimCD4+ T cells expressed a broad TCRVβ repertoire and could readily differentiate into functional T helper cells. Strikingly, no expansion of CD45RA+CD25dimCD8+ T cells was detected with aging, thereby implying that maintenance of naive CD4+ T cells is uniquely regulated. Our data provide novel insight into the homeostasis of naive T cells and may guide the development of therapies to preserve or restore immunity in the elderly.
The Brazilian public health system's spending related to ankylosing spondylitis has increased in recent years. An important part of these costs is due to the introduction of new, more expensive health technologies, as in the case of nuclear magnetic resonance and, mainly, the incorporation of anti-tumour necrotic factor therapy into the therapeutic arsenal. The mean annual direct and indirect cost to the Brazilian public health system to treat a patient with ankylosing spondylitis, according to our findings, is US$ 23,183.56.
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