自身抗體-抗細胞因子抗體

<p class="MsoNormal"><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;">1<font face="宋體">．致病效果 抗細胞因子抗體的致病性沒有清楚，可是上述自身抗體的</font><font face="Calibri">Fab</font><font face="宋體">片段具有特異性低、高親和力結合相應細胞因子的才能。實際上，在正常人血清中抗</font><font face="Calibri">IL-la</font><font face="宋體">，</font><font face="Calibri">IL-6</font><font face="宋體">的自身抗體是其惟一且重要的結合蛋白。雖然現在對血清中的</font><font face="Calibri">IgG</font><font face="宋體">可以進行分類檢測，但</font><font face="Calibri">IFN</font><font face="宋體">&alpha;、</font><font face="Calibri">IL10</font><font face="宋體">的自身抗體卻無法檢測到。</font></span><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;"><o:p></o:p></span></p> <p class="MsoNormal"><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;">或許的原因是自身抗體與其相應的細胞因子以免疫復合物的構成存在于血清中，或者是血清中存在某種克制因子。欲將復合物中的抗原、抗體分開，因抗體的高親和力而不易抵達意圖。</span><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;"><o:p></o:p></span></p> <p class="MsoNormal"><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;">至今仍未理解針對這些細胞因子的高親和力的自身抗體為什么發生、是怎樣發生的。這些自身抗體在體外能中和細胞因子，是否在體內也是這樣，是否他們具有載體或保護細胞因子的功用等等都沒有明了。</span><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;"><o:p></o:p></span></p> <p class="MsoNormal"><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;"><font face="宋體">可是，以細胞因子</font>-IgG<font face="宋體">復合物的方法使循環中的細胞因子得以安穩存在，這一點值得是肯定的。由此也從藥動力學上解說了用抗</font><font face="Calibri">IL-6</font><font face="宋體">抗體治療的患者中為什么出現細胞因子累積，原因是細胞因子</font><font face="Calibri">-IgG</font><font face="宋體">復合物較長的半衰期。</font></span><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;"><o:p></o:p></span></p> <p class="MsoNormal"><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;"><font face="宋體">可是，研討也發現抗細胞因子特異抗體的</font>Fab<font face="宋體">段可以中和性結合上述細胞因子，其結合十分特異、高親和力。細胞因子中和抗體的出現或許會中和其生物活性，而導致細胞因子治療的失利。</font></span><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;"><o:p></o:p></span></p> <p class="MsoNormal"><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;">IL-l<font face="宋體">&alpha;是活化</font><font face="Calibri">T</font><font face="宋體">細胞的一種重要協同刺激因子，一同也或許是</font><font face="Calibri">Th2</font><font face="宋體">細胞的一種自分泌生長因子，因而，作為天然的免疫調節因子，抗</font><font face="Calibri">IL-l</font><font face="宋體">&alpha;抗體特別有意義。通過結合可溶性和膜相關</font><font face="Calibri">IL-la</font><font face="宋體">，克制細胞因子兩種方法的活性，抗</font><font face="Calibri">IL-l</font><font face="宋體">&alpha;自身抗體勢必會影響</font><font face="Calibri">IL1</font><font face="宋體">&alpha;的功用。</font></span><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;"><o:p></o:p></span></p> <p class="MsoNormal"><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;">2<font face="宋體">．檢測方法 檢測抗細胞因子抗體的方法有兩大類。即生物學方法和免疫學方法。免疫學方法包含：</font><font face="Calibri">ELISA</font><font face="宋體">、放射免疫分析（</font><font face="Calibri">RIA</font><font face="宋體">）、免疫放射測定法、蛋白質印跡法（免疫印跡法）；</font></span><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;"><o:p></o:p></span></p> <p class="MsoNormal"><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;">生物學方法主要是檢測細胞因子的各種生物學功用，如克制實驗、抗</span><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;">b<font face="宋體">毒</font></span><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;"><font face="宋體">中和實驗（抗</font>-IFN<font face="宋體">抗體）、</font><font face="Calibri">ILq</font><font face="宋體">抗體的中性粒細胞吸附克制實驗以及胸腺細胞增殖克制實驗。</font></span><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;"><o:p></o:p></span></p> <p class="MsoNormal"><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;">3<font face="宋體">．意義抗</font><font face="Calibri">IL-l</font><font face="宋體">&alpha;抗體含量在免疫性疾病中變化相當大；類風濕關節炎和全身性硬化癥患者中抗</font><font face="Calibri">IL-6</font><font face="宋體">的高親和力自身抗體水平增高。與之相反，抗</font><font face="Calibri">IL-l</font><font face="宋體">&alpha;抗體不出現在一般免疫炎性疾病，包含克隆病。酒精性肝硬化患者出現這些自身抗體意味著預后不良。測方法學上的缺乏阻止了細胞因子自身抗體意義的研討。低水平細胞因子自身抗體對疾病發展無關緊要，或許僅僅反映在活動性炎癥中相關細胞因子組成添加，隨同自身抗體的增高</font></span><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;"><o:p></o:p></span></p> <p class="MsoNormal"><span style="mso-spacerun:'yes';font-family:宋體;mso-ascii-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;">&nbsp;</span><span style="mso-spacerun:'yes';font-family:Calibri;mso-fareast-font-family:宋體;mso-bidi-font-family:'Times New Roman';font-size:9.0000pt;mso-font-kerning:1.0000pt;"><o:p></o:p></span></p>