New Perspectives in Rheumatology: May You Live in Interesting Times: Challenges and Opportunities in Lupus Research.
New Perspectives in Rheumatology: May You Live in Interesting Times: Challenges and Opportunities in Lupus Research.
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DOI：
10.1002/art.40109
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Sanz I
中科院分区：
文献类型：
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作者：
Sanz I
“这是最好的时代，这是最坏的时代，这是智慧的时代，这是愚蠢的时代，这是信仰的时代，这是怀疑的时代，这是光明的季节，这是黑暗的季节，这是希望的春天，这是绝望的冬天，我们面前有一切，我们面前什么也没有....。”查尔斯·狄更斯：《双城记》在回顾狼疮研究的现状时，人们可能会想起狄更斯对他最著名的小说之一的介绍。毕竟，对狼疮发病机制和治疗的研究就像过山车一样，越来越多的有希望的线索变成了明显的死角和失望，最近又一次证明了具有强大科学依据和有希望的II期结果的药物III期试验的失败（epratuzumab） 1，或者在早期研究中缺乏有效信号的途径（抗ifn γ） 2。epratuzumab未能达到EMBLEM研究的主要终点尤其令人痛苦，因为这种抗cd22抗体靶向激活成熟B细胞，长期以来被认为在SLE中起致病作用，从而延长了抗cd20抗体先前的阴性结果。尽管belimumab获得批准并在临床上广泛使用，但TNF超家族受体的其他拮抗剂（包括atacicept （TACI-Ig融合蛋白阻断BLyS和APRIL）和tabalumab（人IgG4 mAb结合可溶性和膜结合BLyS））的阴性或不一致的结果也引发了关于抗B细胞药物的有效性和最佳利用的其他问题。与此同时，仍然需要更好的治疗方法，有证据表明，即使在2000年代，IV级狼疮肾炎的终末期肾脏疾病的风险在15年内可能超过40% 3，并且持续疾病缓解的罕见性，只有15%的患者完全缓解3年，不到4%的患者达到这种理想的结果超过10年4,5,6,7。
“It was the best of times, it was the worst of times, it was the age of wisdom, it was the age of foolishness, it was the epoch of belief, it was the epoch of incredulity, it was the season of Light, it was the season of Darkness, it was the spring of hope, it was the winter of despair, we had everything before us, we had nothing before us….,”. Charles Dickens, A tale of two citiesIn reflecting on the state of affairs in lupus research one could be forgiven for recalling Dickens’ introduction to one of his best known novels. After all, research into the pathogenesis and treatment of lupus can resemble a rollercoaster with an ever growing number of promising leads turning into apparent dead ends and disappointment as recently illustrated yet again by the failure of phase III trials of drugs with strong scientific rationale and promising phase II results (epratuzumab) 1 or lack of efficacy signals in early studies of well-documented pathways (anti-IFNγ) 2. The failure of epratuzumab to meet the primary endpoint in the EMBLEM study was particularly bitter given that this anti-CD22 antibody targets activated mature B cells, long-thought to play a pathogenic role in SLE thereby extending previous negative results with anti-CD20 antibodies. Despite the approval and rather extensive clinical use of belimumab, additional questions about the efficacy and best utilization of anti-B cell agents are also raised by negative or inconsistent results obtained with other antagonists of TNF superfamily receptors that regulate B cell tolerance, activation and survival including atacicept (TACI-Ig fusion protein blocking BLyS and APRIL) and tabalumab (human IgG4 mAb binding soluble and membrane-bound BLyS) 2. All the while, there continues to be a great need for better treatments as indicated by evidence that even in the 2000’s the risk of end-stage renal disease may be over 40% over 15 years in class IV lupus nephritis 3, and by the rarity of sustained disease remissions with only 15% of patients staying in complete remission for 3 years and less than 4% achieving this desirable outcome for more than 10 years 4, 5, 6, 7.
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DOI：
10.1002/art.39856
发表时间：
2017-02
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
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作者：
Clowse ME;Wallace DJ;Furie RA;Petri MA;Pike MC;Leszczyński P;Neuwelt CM;Hobbs K;Keiserman M;Duca L;Kalunian KC;Galateanu C;Bongardt S;Stach C;Beaudot C;Kilgallen B;Gordon C;EMBODY Investigator Group
通讯作者：
EMBODY Investigator Group
影响因子：
64.5
作者：
Davis MM
通讯作者：
Davis MM
影响因子：
13.3
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Chiche, Laurent;Jourde-Chiche, Noemie;Whalen, Elizabeth;Presnell, Scott;Gersuk, Vivian;Dang, Kristen;Anguiano, Esperanza;Quinn, Charlie;Burtey, Stephane;Berland, Yvon;Kaplanski, Gilles;Harle, Jean-Robert;Pascual, Virginia;Chaussabel, Damien
通讯作者：
Chaussabel, Damien
DOI：
10.1084/jem.20151876
发表时间：
2016-05-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Caielli S;Athale S;Domic B;Murat E;Chandra M;Banchereau R;Baisch J;Phelps K;Clayton S;Gong M;Wright T;Punaro M;Palucka K;Guiducci C;Banchereau J;Pascual V
通讯作者：
Pascual V
影响因子：
--
作者：
Couzi, Lionel;Merville, Pierre;Blanco, Patrick
通讯作者：
Blanco, Patrick