TY - JOUR A1 - Seefried, Lothar A1 - Dahir, Kathryn A1 - Petryk, Anna A1 - Högler, Wolfgang A1 - Linglart, Agnès A1 - Martos‐Moreno, Gabriel Ángel A1 - Ozono, Keiichi A1 - Fang, Shona A1 - Rockman‐Greenberg, Cheryl A1 - Kishnani, Priya S T1 - Burden of Illness in Adults With Hypophosphatasia: Data From the Global Hypophosphatasia Patient Registry JF - Journal of Bone and Mineral Research N2 - Hypophosphatasia (HPP) is a rare, inherited, metabolic disease caused by deficient tissue non‐specific alkaline phosphatase activity. This study aims to assess patient‐reported pain, disability and health‐related quality of life (HRQoL) in a real‐world cohort of adults with HPP who were not receiving asfotase alfa during the analysis. Adults (≥18 years old) with HPP (confirmed by ALPL gene mutation and/or low serum alkaline phosphatase activity for age/sex) were identified from the Global HPP Registry (NCT02306720). Demographics, clinical characteristics, and data on patient‐reported pain, disability, and HRQoL (assessed by Brief Pain Inventory Short Form [BPI‐SF], Health Assessment Questionnaire Disability Index [HAQ‐DI], and 36‐Item Short‐Form Health Survey version 2 [SF‐36v2], respectively) were stratified by pediatric‐ and adult‐onset HPP and summarized descriptively. Of the 304 adults included (median [min, max] age 48.6 [18.8, 79.8] years; 74% women), 45% had adult‐onset HPP and 33% had pediatric‐onset HPP (unknown age of onset, 22%). Of those with data, 38% had experienced ≥5 HPP manifestations and 62% had a history of ≥1 fracture/pseudofracture. Median (Q1, Q3) BPI‐SF scores were 3.5 (1.5, 5.3) for pain severity and 3.3 (0.9, 6.2) for pain interference. Median (Q1, Q3) disability on the HAQ‐DI was 0.3 (0.0, 0.7). Median (Q1, Q3) physical and mental component summary scores on the SF‐36v2 were 42.4 (32.7, 49.9) and 45.3 (36.3, 54.8), respectively. Greater numbers of HPP manifestations experienced/body systems affected correlated significantly with poorer scores on the BPI‐SF, HAQ‐DI, and SF‐36v2 (all p < 0.05). No significant differences between adults with pediatric‐ and adult‐onset HPP were observed for patient‐reported outcomes, except for disability and the BPI‐SF question “pain at its worst,” which were significantly higher among adults with pediatric‐ versus adult‐onset HPP (p = 0.03 and 0.04, respectively). These data from the Global HPP Registry show that adults with HPP have a substantial burden of illness that is associated with reduced patient‐reported HRQoL, regardless of age of disease onset. KW - assistive devices KW - bone fractures KW - pain KW - pseudofractures KW - quality of life Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-217787 VL - 35 IS - 11 SP - 2171 EP - 2178 ER - TY - JOUR A1 - Prelog, Martina A1 - Schönlaub, Jörn A1 - Würzner, Reinhard A1 - Koppelstaetter, Christian A1 - Almanzar, Giovanni A1 - Brunner, Andrea A1 - Gasser, Martin A1 - Prommegger, Rupert A1 - Häusler, Gabriele A1 - Kapelari, Klaus A1 - Högler, Wolfgang T1 - Lower CD28+ T cell proportions were associated with CMV-seropositivity in patients with Hashimoto’s thyroiditis JF - BMC Endocrine Disorders N2 - Background Alterations in the naive T cell subpopulations have been demonstrated in patients with T cell mediated autoimmune disorders, reminiscent of immunological changes found in the elderly during immunosenescence, including the switch from CD45RA + to CD45RO + T cells and decreased thymic function with increased compensatory proliferative mechanisms, partly associated with latent Cytomegalovirus (CMV) infection. The present study was aimed to investigate proportions of lymphocytes, their relation to CMV-seropositivity and the replicative history of CD45RA + expressing T cells in Hashimoto’s thyroiditis (HT, n = 18) and healthy controls (HC, n = 70). Methods Proportions of peripheral T cells were investigated by flow cytometry. The replicative history was assessed by T cell receptor excision circles (TRECs) and relative telomere length (RTL). Expression of CD62L was analyzed by immunohistochemistry in thyroid sections. The role of CMV was assessed by serology, ELISPOT assay and in situ hybridization. Results Our results demonstrated a significant increase of CD28-negative T cells, associated with CMV-seropositivity in HT patients. HT showed abundant CD45RO + T cells with peripheral loss of CD62L-expressing CD8 + CD45RA + T cells, the latter mainly depending on disease duration. CD62L was expressed in thyroid lymphocyte infiltrations. The diagnosis of HT and within the HT group CMV-seropositivity were the main determinants for the loss of CD28 expression. RTL was not different between HC and HT. HT showed significantly lower TRECs in CD4 + CD45RA + T cells compared to HC. Conclusions Patients with HT display a peripheral T cell phenotype reminiscent of findings in elderly persons or other autoimmune disorders. Whether these mechanisms are primary or secondary to the immunological alterations of autoimmune conditions should be investigated in longitudinal studies which may open research on new therapeutic regimes for treatment of HT and associated autoimmune diseases. KW - Immunosenescence KW - CD62L KW - Regulatory T cells KW - TREC KW - Telomere Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96352 UR - http://www.biomedcentral.com/1472-6823/13/34 ER -