行政院國家科學委員會專題研究計畫成果報告:HLA-Cw6 基因特異性及其多形性殘基與台灣無關節痛型尋常性乾癬易受性相關

尋常性乾癬是一種慢性發炎的表 皮增生皮膚疾病，具有多重病因及不同 遺傳型式。染色體6P（人類白血球抗 原，HLA 區域）及17q 是己被確認的乾 癬易受性基因所在。以血清學方法或基 因分析法，分析HLA 的報告中，HLACw* 06 是最常被報告為與早發型尋常 性乾癬相關者。本研究探討台灣68 位 乾癬人（32 位有關節痛，36 位無關節 痛），以及213 位無乾癬之正常人之 HLA-Cw 基因特異性。以多元脢鍵反應 ／ 特異性序列寡核甘探針雜化系統 （PCR-SSOPH）方法分析，並以巢狀多 元脢脢鍵反應（nested PCR）進一步分 析一些亞特異型，對上述三組病人做比 較之結果為HLA-Cw*06 與無關節痛型 尋常性乾癬相關。進一步比較其HLACw* 06 多形性殘基，顯示亦與無關節痛 型尋常性乾癬具強相關。此資料顯示 HLA-Cw6 與無關節痛型尋常性乾癬之 發生有關。而是否HLA-Cw6á chain 或 其他HLA-Cw6 之密切相連基因造成此 病，則需進一步研究。此外，由於Ala 73，Asn77/Lys80, Asp 90 為與natural killer cell inhibitory receptors (NKIRs) 作用之關鍵多形性殘基，我們臆測在乾 癬表皮浸潤之CD8+淋巴球之natural killer cell-like activity 之被抑制，參與了 乾癬的致病過程。Psoriasis vulgaris (PSV) is a chronic inflammatory and hyperproliferative skin disease. It is multifactorial and heterogenetically inherited. Psoriasis susceptibility loci on chromosomes 6p (HLA region) and 17q was confirmed by microsatellite technique on family study. Using serological techniques and genotyping method, the most constant association with human histocompatibility antigens (HLA) was found in patients with type I (early onset) PSV with HLA-Cw*06. Genotyping on each HLA-Cw specificities of both 68 Taiwanese PSV patients (32 patients with arthralgia and 36 without arthralgia) and 213 non-psoriatic control subjects of the Taiwanese population was conducted by polymerase chain reaction/ sequencespecific oligonucleotide probe hybridization (PCR-SSOPH) of HLA-Cw geneand , and several subspecificities were confirmed by nested polymerase chain reaction. The HLA-Cw specificities were compared among the patients with arthralgia, patients without arthralgia and control groups. The results showed that the HLA-Cw*06 specificity was significantly associated with PSV without arthralgia (20.8 % of PSV without arthralgia versus 5.2 % of control, Odd’s ratio (O.R.)=4.85, P£ 10-4). The amino acid residues on the heavy chain of the HLA-Cw antigens that positively associated with PSV were further analyzed for their association with susceptibility of PSV. It revealed a strong association of Asp 9, Ser 24, Ala 73, Asn 77/Lys 80, Asp 90 and Trp 156 ( Pc £ 0.006, 0.027, 0.005, 0.0000, 0.0018 and 0.024 respectively) with PSV patients without arthralgia. This report also point to an important association of HLA-Cw6 and the development of PSV without arthralgia. Whether the gene encoding HLA-Cw6 a chain or other gene(s) in close linkage with it might contribute to PSV needs further investigation. On the other hand, as both Ala73 and Asp 90 were reported key residues for interaction with the natural killer cell inhibitory receptors (NKIRs), we speculate an inhibition of natural killer cell-like activity of infiltrating CD8+ cells in psoriatic epithelium by HLA-Cw6 antigens might involved in the pathogenesis of PSV