Inorganic pyrophosphate is reduced in patients with systemic sclerosis.
Inorganic pyrophosphate is reduced in patients with systemic sclerosis.
复制标题
DOI：
10.1093/rheumatology/keab508
复制
发表时间：
2022-03-02
期刊：
影响因子：
5.5
通讯作者：
Varga, John
中科院分区：
文献类型：
--
作者：
Hsu, Vivien M.;Kozak, Eszter;Li, Qiaoli;Bocskai, Marta;Schlesinger, Naomi;Rosenthal, Ann;McClure, Scott T.;Kovacs, Laszlo;Laszlo, Balint Balint;Szamosi, Szilvia;Szucs, Gabriella;Carns, Mary;Aren, Kathleen;Goldberg, Isaac;Varadi, Andras;Varga, John
皮肤钙质沉着症是系统性硬化症（SSc）的致残性并发症，其发病机制尚不清楚，缺乏有效的治疗方法。无机焦磷酸盐（PPi）是异位矿化的关键调节剂，其缺乏与异位矿化障碍有关。因此，我们试图检验这一假设，即SSc可能与循环PPi减少有关，这可能在皮肤钙质沉着症中起致病作用。从罗格斯大学和西北大学（美国队列）以及塞格德大学和德布勒森大学（匈牙利队列）的门诊流变学诊所招募SSc受试者和年龄匹配的无SSc对照受试者。皮肤钙质沉着症可通过直接触诊、影像学检查或两者同时进行确认。在过量腺苷5'磷酸硫酸盐存在下，使用ATP硫酸化酶将PPi转化为ATP，在无血小板血浆中测定血浆PPi水平。美国队列入组了81例SSc患者（40例弥漫性皮肤SSc和41例局限性皮肤SSc），匈牙利队列入组了45例SSc患者（19例弥漫性皮肤SSc和26例局限性皮肤SSc）。经常检测到钙质沉着症（40%的美国和46%的匈牙利队列）。血浆PPi水平在有和没有钙质沉着的SSc队列中均显著降低（美国：p=0.003;匈牙利：p<0.001）。在有或没有钙质沉着的SSc患者中，循环PPi显著降低。PPi降低可能在钙质沉着症的病理生理学中很重要，并导致慢性SSc的组织损伤。给予PPi可能是一种治疗策略，计划进行更大规模的临床研究以证实我们的发现。
The pathogenesis of calcinosis cutis, a disabling complication of systemic sclerosis (SSc), is poorly understood and effective treatments are lacking. Inorganic pyrophosphate (PPi) is a key regulator of ectopic mineralization, and its deficiency has been implicated in ectopic mineralization disorders. We therefore sought to test the hypothesis that SSc may be associated with reduced circulating PPi, which might play a pathogenic role in calcinosis cutis. Subjects with SSc and age-matched controls without SSc were recruited from the outpatient Rheumatology clinics at Rutgers and Northwestern Universities (US cohort), and from the Universities of Szeged and Debrecen (Hungarian cohort). Calcinosis cutis was confirmed by direct palpation, by imaging, or both. Plasma PPi levels were determined in platelet-free plasma using ATP sulfurylase to convert PPi into ATP in the presence of excess adenosine 5’ phosphosulfate. Eighty-one patients with SSc (40 diffuse cutaneous, and 41 limited cutaneous SSc) in the US cohort and 45 patients with SSc (19 diffuse cutaneous and 26 limited cutaneous SSc) in the Hungarian cohort were enrolled. Calcinosis was frequently detected (40% of US and 46% of the Hungarian cohort). Plasma PPi levels were significantly reduced in both SSc cohorts with and without calcinosis (US: p=0.003; Hungarian: p<0.001). Circulating PPi are significantly reduced in SSc patients with or without calcinosis. Reduced PPi may be important in the pathophysiology of calcinosis and contribute to tissue damage with chronic SSc. Administering PPi may be a therapeutic strategy and larger clinical studies are planned to confirm our findings.
登录
查看更多内容
DOI：
10.1016/j.jid.2015.10.065
发表时间：
2016-03
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Li Q;Arányi T;Váradi A;Terry SF;Uitto J
通讯作者：
Uitto J
DOI：
10.1073/pnas.1319582110
发表时间：
2013-12-10
影响因子：
11.1
作者：
Jansen, Robert S.;Kucukosmanoglu, Asli;van de Wetering, Koen
通讯作者：
van de Wetering, Koen
影响因子：
11.1
作者：
Dedinszki D;Szeri F;Kozák E;Pomozi V;Tőkési N;Mezei TR;Merczel K;Letavernier E;Tang E;Le Saux O;Arányi T;van de Wetering K;Váradi A
通讯作者：
Váradi A
线粒体，衰老和细胞衰老：对硬皮病的影响。
影响因子：
5
作者：
Bueno M;Papazoglou A;Valenzi E;Rojas M;Lafyatis R;Mora AL
通讯作者：
Mora AL
影响因子：
3.4
作者：
Hsu V;Bramwit M;Schlesinger N
通讯作者：
Schlesinger N