Genetic analysis of MPO variants in four psoriasis subtypes in patients from Germany.
Genetic analysis of MPO variants in four psoriasis subtypes in patients from Germany.
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德国患者四种银屑病亚型 MPO 变异的遗传分析
DOI：
10.1016/j.jid.2021.01.017
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
A. Weye
中科院分区：
文献类型：
--
作者：
Haskamp;J. S. Horowitz;V. Oji;S. Philipp;M. Sticherling;K. Schakel;S. Schuhmann;J. C. Prinz;H. Burkhardt;F. Behrens;B. Bohm;M. Kohm;J. Rech;D. Simon;G. Schett;K. Morrison;S. Gerdes;G. Assmann;A. Nimeh;V. Schuster;A. Jacobi;A. Weye
银屑病是一种常见的炎症性皮肤病，严重影响患者的生活质量。最常见的银屑病形式是寻常型银屑病（PsV），其特征在于分界的、肿胀的、凸起的斑块沿着有银色鳞片。高达30%的PsV患者发展为称为银屑病关节炎（PsA）的炎性关节疾病（Mease等人，2013;赖希等人，2009年）。PsV和PsA是遗传上复杂的疾病，在一种或两种银屑病亚型中鉴定出> 65个易感性基因座（Tsalvet al.，2017年）。与PsV和PsA相反，脓疱型银屑病亚型掌跖脓疱型银屑病或掌跖脓疱病（PPP）和泛发性脓疱型银屑病（GPP）更罕见。PPP的特征是局限性表皮中性粒细胞脓疱，而在严重的多系统炎症中更广泛的脓疱是GPP的典型特征。PPP的遗传病因学尚未解决;在英国患者中报道了与IL 36 RN（编码IL-36受体拮抗剂）变体相关的不一致结果（Adhives et al.，2019）与德国和爱沙尼亚患者（Mössner et al.，2018年）。相反，IL 36 RN已被认为是GPP的主要基因（Marrakchi et al.，2011），尽管进一步的因素有助于GPP的发病机制，并且讨论了寡基因遗传（Mössner et al.，2018年）。诊断为滑膜炎、痤疮、脓疱病、骨质增生、骨炎综合征的患者表现出炎性皮肤和骨骼疾病的不同组合，与常见的银屑病亚型和脓疱性银屑病相当重叠;滑膜炎、痤疮、脓疱病、骨质增生、骨炎综合征的遗传基础在很大程度上是未知的。2020; Vergnano等人，2020年）。嗜中性粒细胞酶MPO的缺乏损害垂死的嗜中性粒细胞的吞噬作用并增加IL-36活化蛋白酶的活性，从而驱动脓疱中的炎症（Haskamp等人，2020年）。此外，具有MPO变体的GPP患者比没有MPO变体的患者更可能具有PPP、舌表现和银屑病阳性家族史（Haskamp等人，2020年）;在患有PsV和PsA的患者中检测到MPO的血清量增加，这表明MPO变体在常见的银屑病表现中具有潜在的保护作用（Ketzu等，2018年）。这些发现促使我们研究MPO变异体在其他银屑病亚型中的作用。
Psoriasis is a common inflammatory skin disorder with a strong impact on patients’ QOL. The most common psoriasis form, psoriasis vulgaris (PsV), is characterized by demarcated, erythematous, raised plaques along with silvery scales. Up to 30% of patients with PsV develop an inflammatory joint disease named psoriatic arthritis (PsA)(Mease et al., 2013; Reich et al., 2009). PsV and PsA are genetically complex diseases with> 65 susceptibility loci identified in one or both psoriatic subtypes (Tsoi et al., 2017). In contrast to PsV and PsA, pustular psoriatic subtypes—palmoplantar pustular psoriasis or palmoplantar pustulosis (PPP) and generalized pustular psoriasis (GPP)—are rarer. PPP is characterized by localized epidermal neutrophil pustules, whereas more generalized pustules in severe multisystemic inflammation are typical for GPP. The genetic etiology of PPP is unsolved; discrepant results related to association with IL36RN (encoding the IL-36 receptor antagonist) variants were reported in British patients (Twelves et al., 2019) versus in German and Estonian patients (Mössner et al., 2018). Conversely, IL36RN has been acknowledged as a major gene for GPP (Marrakchi et al., 2011), although further factors contribute to the pathogenesis of GPP, and oligogenic inheritance is discussed (Mössner et al., 2018). Patients diagnosed with syndrome of synovitis, acne, pustulosis, hyperostosis, osteitis exhibit different combinations of inflammatory skin and bone diseases considerably overlapping with common psoriatic subtypes and pustular psoriasis; the genetic basis of syndrome of synovitis, acne, pustulosis, hyperostosis, osteitis is largely unknown.Recently, we and others identified MPO as an additional major susceptibility gene in GPP (Haskamp et al., 2020; Vergnano et al., 2020). The deficiency of neutrophilic enzyme MPO impairs phagocytosis of dying neutrophils and increases the activity of IL-36 activating proteases, thereby driving inflammation in pustules (Haskamp et al., 2020). In addition, patients with GPP with MPO variants are more likely to have PPP, tongue manifestations, and a positive family history of psoriasis than those without MPO variants (Haskamp et al., 2020); an increased serum amount of MPO has been detected in patients with PsV and PsA, suggesting a potentially protective role of MPO variants in common psoriatic manifestations (Cretu et al., 2018). These findings prompted us to investigate the role of MPO variants in other psoriatic subtypes.
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影响因子：
9.8
作者：
Haskamp, Stefan;Bruns, Heiko;Hueffmeier, Ulrike
通讯作者：
Hueffmeier, Ulrike
DOI：
10.1016/j.jaci.2018.06.038
发表时间：
2019-03
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Twelves S;Mostafa A;Dand N;Burri E;Farkas K;Wilson R;Cooper HL;Irvine AD;Oon HH;Kingo K;Köks S;Mrowietz U;Puig L;Reynolds N;Tan ES;Tanew A;Torz K;Trattner H;Valentine M;Wahie S;Warren RB;Wright A;Bata-Csörgő Z;Szell M;Griffiths CEM;Burden AD;Choon SE;Smith CH;Barker JN;Navarini AA;Capon F
通讯作者：
Capon F
影响因子：
10.3
作者：
Mossner, R.;Wilsmann-Theis, D.;Hueffmeier, U.
通讯作者：
Hueffmeier, U.
DOI：
10.1016/s0021-9258(17)42244-7
发表时间：
1994-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
William;Nauseee;Susan Brigham;M. Cogley
通讯作者：
William;Nauseee;Susan Brigham;M. Cogley
影响因子：
3.9
作者：
Marchetti, C;Patriarca, P;Romano, M
通讯作者：
Romano, M