Kolb G, Eckle I, Heidtmann H H, Neurath F, Havemann K
Abteilung Hämatologie/Onkologie/Immunologie, Universitätsklinikum, Marburg.
Scand J Rheumatol Suppl. 1988;75:179-89. doi: 10.3109/03009748809096760.
Expression of neoantigens during denaturation of IgG by oxygen radicals or proteolysis was assumed to be a possible mechanism for stimulation of rheumatoid factor (RF) formation and/or granulocyte dependent inflammative joint destruction. The so-called human leukocyte elastase (HLE) regularly released by stimulated neutrophils f.e. into the RA synovial fluid is known to split IgG in vitro into papain like fragments and low molecular weight peptides. The n-terminal site of the HLE related Fc is bearing a neoantigenic group which is located near the hinge region but not expressed by the native IgG. The neoantigen itself is represented by the low molecular weight peptides produced by prolonged HLE-IgG proteolysis. Detection of HLE generated Fc in synovial fluids was performed by radioimmunoassay specific for the neoantigen. Patients were divided into the three groups; I RA (n = 23), II inflammative joint effusions except RA (n = 23), III osteoarthritis and trauma (n = 19). The biological effect of the neoantigen on to granulocyte oxidative metabolism was tested by Cytochrome C reduction and chemiluminescence. Neoantigen bearing Fc could be detected in 15 of 23 cases of group I, in group II in 11 of 23 cases and only in 7 of 19 cases in group III. The median concentrations were 0.62 micrograms in group I and zero in II and III. The HLE derived Fc were able to inhibit the oxidative metabolism of activated granulocytes in vitro. The O2- production of stimulated granulocytes was depressed dose dependent by the neoantigen. The neoantigenic group itself does not react with RF as proved by nephelometric titration of HLE derived Fc, neoantigenic peptide and native IgG against a RF standard.
氧自由基或蛋白水解作用使IgG变性过程中新抗原的表达被认为是刺激类风湿因子（RF）形成和/或粒细胞依赖性炎性关节破坏的一种可能机制。例如，受刺激的中性粒细胞经常释放到类风湿关节炎（RA）滑液中的所谓人白细胞弹性蛋白酶（HLE），已知在体外可将IgG裂解为木瓜蛋白酶样片段和低分子量肽。与HLE相关的Fc的N末端位点带有一个新抗原基团，该基团位于铰链区附近，但天然IgG不表达。新抗原本身由HLE-IgG长时间蛋白水解产生的低分子量肽代表。通过针对新抗原的放射免疫测定法检测滑液中HLE产生的Fc。患者分为三组：I组为RA（n = 23），II组为除RA外的炎性关节积液（n = 23），III组为骨关节炎和创伤（n = 19）。通过细胞色素C还原和化学发光测试新抗原对粒细胞氧化代谢的生物学效应。I组23例中有15例可检测到带有新抗原的Fc，II组23例中有11例，III组19例中仅7例可检测到。I组的中位浓度为0.62微克，II组和III组为零。HLE衍生的Fc能够在体外抑制活化粒细胞的氧化代谢。新抗原剂量依赖性地抑制受刺激粒细胞的O2-产生。通过用HLE衍生的Fc、新抗原肽和天然IgG针对RF标准品进行比浊滴定证明，新抗原基团本身不与RF反应。
