Targeting TNFα in severe psoriasis-mass spectrometry reveals a time-dependent specific inhibition of Factor H in responding patients

American Journal of Translational Research

Joana F Antunes¹  Pedro M Domingues²  Francisco M Amado³  Patrice Morlière⁴  João A Ferreira⁵  Ana C Guerreiro⁶  Virginie Nourry⁷ 

[1] CHU Amiens, Ple Biologie, Pharmacie et Sant des Populations, Centre de Biologie Humaine, Laboratoire de Biochimie, Avenue Ren Lannec-Saloul, 80054 Amiens, France;Department of Chemistry and QOPNA, University of Aveiro, Campus Universitrio de Santiago, 3810-193 Aveiro, Portugal;Hospital de Santa Maria, Faculdade de Medicina de Lisboa, Clnica Dermatologica Universitaria and, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa., Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal;INSERM, U1088, 1 Rue Des Louvels, 80037 Amiens, France;Musum National dHistoire Naturelle, Dpartement Adaptations Du Vivant, 43 Rue Cuvier, 75231 Paris, France;Universit de Picardie Jules Verne, UFR de Mdecine, 1 Rue Des Louvels, 80036 Amiens, France;Universit de Picardie Jules Verne, UFR de Pharmacie, 1 Rue Des Louvels, 80036 Amiens, France

关键词: Etanercept®;    TNFα;    psoriasis;    serum;    mass spectrometry;    complement factor H;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Drugs targeting TNFα (eg, Etanercept®) provide effective control of severe psoriasis. In absence of validated biological parameters of inflammation in psoriasis most decisions on therapeutics have relied mostly on clinical criteria, namely the “Psoriasis Area and Severity Index” (PASI). The purpose of this study was to assess by mass spectrometry alterations in concentrations of serum proteins that specifically correlated with effectiveness of Etanercept treatment. This prospective study enrolled 10 patients suffering from moderate to severe psoriasis (PASI score > 10 and < 17) and treated with Etanercept over a period of 24 weeks; 10 healthy, age-matched volunteers provided controls. Serum proteins sensitive to Etanercept treatment were identified using SELDI-TOF (surface-enhanced laser desorption and ionization - time of flight) coupled to nano LC-ESI/MS (nano liquid chromatography-electrospray ionization/tandem mass spectrometry) technologies. For comparisons between groups of individuals p-values (considered significant when < 0.01) were estimated with non-parametric tests, namely Mann-Whitney (for unpaired data) and Wilcoxon signed-rank (for paired data). In responding patients it could be shown using SELDI-TOF spectrometry that two proteins (134 kDa and 4.3 kDa) return to control levels by 24 weeks of treatment. Using nano LC-ESI/MS the 134 kDa species was identified as complement Factor H. These observations deserve further analyses utilizing larger cohorts of patients. Determination of Factor H levels may become a complementary tool to follow remission or predict the onset of relapse in the follow-up of patients under treatment with Etanercept.

【 授权许可】

CC BY-NC