Yamada Hiromichi, Itoh Akira, Hatanaka Yoshihiro, Tsukiji Misuzu, Takamori Kenji
Department of Dermatology, International Goodwill Hospital, Izumi-ku, Yokohama, Japan.
Ther Apher Dial. 2010 Jun;14(3):292-7. doi: 10.1111/j.1744-9987.2010.00827.x.
Pemphigus represents a potentially life-threatening, blistering, chronic autoimmune disease involved with autoantibodies against desmosomal adhesion proteins, desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3). These autoantibodies belong to biased immunoglobulin subclasses, predominantly IgG1 and IgG4. Although plasmapheresis is established for the treatment of pemphigus, specific immunoadsorption of the autoantibodies has not been clinically applied. In order to search for a novel adsorbent for the pemphigus autoantibodies, we screened a library of 26 chemical ligand adsorbents using the effluent of double filtration plasmapheresis obtained from pemphigus patients. As a result of the screening, we found that each adsorbent whose ligand is 2-thiophene ethylamine, tryptophan, para-guanidinophenylalanine, phenylalanine, or thienylglycine adsorb both antibodies to Dsg3 and Dsg1 efficiently, in that order. Furthermore, the thiophene adsorbent exhibited a high affinity for the IgG4 subclass. These results suggest that the thiophene adsorbent may be suitable for pemphigus immunoadsorption. Further in vivo animal studies and clinical trials are needed.
天疱疮是一种潜在危及生命的慢性自身免疫性水疱病,与针对桥粒黏附蛋白桥粒芯糖蛋白1(Dsg1)和桥粒芯糖蛋白3(Dsg3)的自身抗体有关。这些自身抗体属于偏向性免疫球蛋白亚类,主要是IgG1和IgG4。虽然血浆置换已用于天疱疮的治疗,但自身抗体的特异性免疫吸附尚未应用于临床。为了寻找一种用于天疱疮自身抗体的新型吸附剂,我们使用从患有天疱疮的患者获得的双重过滤血浆置换的流出物筛选了一个包含26种化学配体吸附剂的文库。筛选结果表明,配体为2-噻吩乙胺、色氨酸、对胍基苯丙氨酸、苯丙氨酸或噻吩基甘氨酸的每种吸附剂,依次对Dsg3和Dsg1的抗体均有高效吸附作用。此外,噻吩吸附剂对IgG4亚类表现出高亲和力。这些结果表明,噻吩吸附剂可能适用于天疱疮免疫吸附。还需要进一步的体内动物研究和临床试验。