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(jié)合相應(yīng)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(jié)合蛋白。雖然現(xiàn)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(yīng)的細胞因子以免疫復(fù)合物的構(gòu)成存在于血清中，或者是血清中存在某種克制因子。欲將復(fù)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(fā)生、是怎樣發(fā)生的。這些自身抗體在體外能中和細胞因子，是否在體內(nèi)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(fù)合物的方法使循環(huán)中的細胞因子得以安穩(wěn)存在，這一點值得是肯定的。由此也從藥動力學(xué)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(xiàn)細胞因子累積，原因是細胞因子</font><font face="Calibri">-IgG</font><font face="宋體">復(fù)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(fā)現(xiàn)抗細胞因子特異抗體的</font>Fab<font face="宋體">段可以中和性結(jié)合上述細胞因子，其結(jié)合十分特異、高親和力。細胞因子中和抗體的出現(xiàn)或許會中和其生物活性，而導(dǎo)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(xié)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(diào)節(jié)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(jié)合可溶性和膜相關(guān)</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(xué)方法和免疫學(xué)方法。免疫學(xué)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(zhì)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(xué)方法主要是檢測細胞因子的各種生物學(xué)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(fēng)濕關(guān)節(jié)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(xiàn)在一般免疫炎性疾病，包含克隆病。酒精性肝硬化患者出現(xiàn)這些自身抗體意味著預(yù)后不良。測方法學(xué)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(fā)展無關(guān)緊要，或許僅僅反映在活動性炎癥中相關(guān)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>