Prediction of spinal radiographic progression in patients with radiographic axial spondyloarthritis under TNF inhibitor therapy with serum biomarkers

Bei der axialen Spondyloarthritis (ax-SpA) handelt es sich um eine chronisch- entzündliche, rheumatische Erkrankung. Das Hauptsymptom ist ein entzündlicher Rückenschmerz, vorrangig im lumbalen Teil der Wirbelsäule, wobei auch systemische Manifestationen wie chronisch-entzündliche Darmerkrankungen (CED), Psoriasis etc. möglich sind. Im Verlauf kommt es zusätzlich zum inflammatorischen Geschehen, zu vermehrt strukturellen Veränderungen des skelettalen Systems mit Osteopenie, osteophytären Anbauten, Syndesmophyten und einer zunehmenden Versteifung der Wirbelsäule. Um PatientInnen mit einem erhöhten Risiko für eine schnelle Progression der Erkrankung frühzeitig zu identifizieren, wurden verschiedene Biomarker auf eine mögliche Prädiktion dieser Progression untersucht. Methodik: Hierfür wurden 137 PatientInnen mit einer radiografischen axialen Spondyloathritis unter TNFa-Inhibitortherapie aus der Groningen Leeuwarden Axial Spondyloarthritis (GLAS) -Kohorte in die Studie eingeschlossen. Zur Baseline, sowie nach 2, 4 und 6 Jahren erfolgten Röntgenaufnahmen und zu Beginn, nach 3 Monaten, 2 und 6 Jahren Blutentnahmen. Eine radiografische Progression wurde entweder als Differenz des Modified Stoke Ankylosing Spondylitis Score (mSASSS) ≥2 nach 2 Jahren, ≥4 nach 4 Jahren und ≥4 nach 6 Jahren oder als Syndesmophytenneubildung ≥1 nach 2 Jahren, ≥2 nach 4 und ≥2 nach 6 Jahren definiert. Die Seren der PatientInnen wurden mittels Sandwich-ELISAs auf die Konzentrationen von 10 Biomarkern untersucht: Matrixmetalloproteinase-3 (MMP-3), Calprotectin, Vascular Endothelial Growth Factor (VEGF), Leptin, Visfatin, Sclerostin, Serum Amyloid A (SAA), High-Molecular-Weight- Adiponektin (HMW-Adiponektin), N-terminal Propeptid des Typ II Kollagens (PIINP) und Osteoprotegerin (OPG). Der Zusammenhang zwischen radiografischer Progression und den einzelnen Biomarkern, Biomarkerkombinationen und Biomarkerverläufen wurde mittels logistischer Regressionsanalyse und Receiver Operating Characteristic (ROC)- Analyse analysiert. Ergebnisse: Calprotectin und Visfatin zeigten eine signifikante Assoziation mit der radiografischen Progression nach 2 Jahren, Leptin eine signifikante Assoziation mit der radiografischen Progression nach 4 Jahren und Leptin und MMP-3 eine signifikante Assoziation mit der radiografischen Progression nach 6 Jahren. Die Biomarkerverläufe von Visfatin und Leptin über den Zeitraum von 2 Jahren wiesen ebenfalls signifikante Ergebnisse auf. Schlussfolgerung: Die Biomarker Visfatin, Calprotectin, Leptin und MMP-3 sind mit einer spinalen radiografischen Progression assoziiert.Axial spondyloarthritis is a chronic, inflammatory rheumatic disease. The main symptom of the disease is inflammatory back pain, although extra-musculoskeletal manifestations such as inflammatory bowel disease or psoriasis might also be present. While the disease is progressing, structural changes of the skeletal systems detectable by X-rays (such as syndemophytes) may occur. This work was aimed at identification of biomarkers with predictive value regarding radiographic spinal progression in patients with axial spondyloarthritis. Method: A total of 137 patients with radiographic axial spondyloarthritis under treatment with TNFa-blockers from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort were included. At Baseline, after 2, 4 and 6 years X-rays were performed and after 3 month, 2 and 6 years blood samples taken. A radiographic progression was either defined as a difference of the Modified Stoke Ankylosing Spondylitis Score (mSASSS) ≥2 after 2 years, ≥4 after 4 years or ≥4 after 6 years or due to syndesmophyte formation ≥1 after 2 years, ≥2 after 4 years or ≥2 after 6 years. The patient’s serum samples were evaluated on biomarker concentrations via Sandwich-ELISAs for the following 10 biomarkers: Matrixmetalloproteinase-3 (MMP-3), Calprotectin, Vascular Endothelial Growth Factor (VEGF), Leptin, Visfatin, Sclerostin, Serum Amyloid A (SAA), High- Molecular-Weight-Adiponektin (HMW-Adiponektin), N-terminal propeptid of type II collagen (PIINP) and Osteoprotegerin (OPG). The association of radiographic spinal progression and the single biomarkers and biomarker combinations were analysed with logistics regression and Receiver Operating Characteristic (ROC) analysis. Results: Calprotectin and Visfatin showed a significant association with radiographic progression after 2 years, Leptin a significant association with radiographic progression after 4 years and MMP-3 and Leptin a significant association with the radiographic progression after 6 years. Changes of the serum level of Visfatin and Leptin over the time of 2 years showed a significant association with radiographic spinal progression as well. Conclusion: The biomarkers Visfatin, Calprotectin, Leptin and MMP-3 are associated with spinal radiographic progression

Teacher Collaboration: Implications for New Mathematics Teachers

One increasingly popular way of supporting new teachers is through the use of mentoring. New teachers are often paired with mentors as one of a number of supports meant to aid new teachers as they begin their career. The various types of mentoring range from school based mentors assigned by the school to specialty mentors, such as math coaches. Examples of other types of supports that are thought of as separate from formal mentoring are lesson studies, professional development schools, professional development workshops supported by local universities, teacher networks and sponsored professional development. Given the popularity of policies promoting support for new teachers, we explore specific supports for new teachers in addition to characteristics of these supports by focusing on two new alternatively certified mathematics. Through observations and both formal and informal interviews that span a year, we gained insight into the various influences on these two teachers’ practice in mathematics and considered how these might inform future practices aimed at supporting new teachers

Role of GSH and Iron-Sulfur Glutaredoxins in Iron Metabolism—Review

Glutathione (GSH) was initially identified and characterized for its redox properties and later for its contributions to detoxification reactions. Over the past decade, however, the essential contributions of glutathione to cellular iron metabolism have come more and more into focus. GSH is indispensable in mitochondrial iron-sulfur (FeS) cluster biosynthesis, primarily by co-ligating FeS clusters as a cofactor of the CGFS-type (class II) glutaredoxins (Grxs). GSH is required for the export of the yet to be defined FeS precursor from the mitochondria to the cytosol. In the cytosol, it is an essential cofactor, again of the multi-domain CGFS-type Grxs, master players in cellular iron and FeS trafficking. In this review, we summarize the recent advances and progress in this field. The most urgent open questions are discussed, such as the role of GSH in the export of FeS precursors from mitochondria, the physiological roles of the CGFS-type Grx interactions with BolA-like proteins and the cluster transfer between Grxs and recipient proteins

Baseline serum biomarkers of inflammation, bone turnover and adipokines predict spinal radiographic progression in ankylosing spondylitis patients on TNF inhibitor therapy

Objective: To analyze whether biomarker levels at baseline or their change after 3 months or 2 years predict radiographic spinal progression in ankylosing spondylitis (AS) patients treated with TNF-α inhibitors (TNFi). Methods: 137 AS patients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort were included before starting TNFi. Serum biomarkers were measured at baseline, 3 months and 2 years: Markers of inflammation (calprotectin, matrix metalloproteinase-3, vascular endothelial growth factor), bone turnover markers (bone-specific alkaline phosphatase, serum C-terminal telopeptide fragments of type I collagen (sCTX), osteocalcin, osteoprotegerin, procollagen type I and II N-terminal propeptide, sclerostin) and adipokines (high-molecular-weight adiponectin, leptin, visfatin). Spinal radiographs were scored at baseline, 2 and 4 years. Logistic regression was performed to examine the association between biomarker values and radiographic spinal progression, adjusting for known risk factors for radiographic progression. Results: Baseline calprotectin and visfatin levels were associated with mSASSS progression ≥2 points (OR 1.195 [95%CI 1.055–1.355] and 1.465 [1.137–1.889], respectively), while calprotectin was also associated with new syndesmophyte formation after 2 years (OR 1.107 [1.001–1.225]). Baseline leptin level was associated with mSASSS progression ≥4 points after 4 years (OR 0.614 [0.453–0.832]), and baseline sCTX level with syndesmophyte formation after 4 years (OR 1.004 [1.001–1.008]). Furthermore, change of visfatin and leptin levels over the first 2 years showed significant association with radiographic progression after 4 years. Conclusion: Independent of known risk factors, serum levels of biomarkers at baseline are able to predict radiographic spinal progression over 2 and 4 years in AS patients on TNFi therapy