肺泡蛋白沉积症患者血清中抗粒-巨噬细胞集落刺激因子抗体等血清学指标的临床意义

Autoantibody against granulocyte macrophage colony- stimulating factor and other serum markers in pulmonary alveolar proteinosis

目的 了解肺泡蛋白沉积症 (PAP)患者血清中抗粒 巨噬细胞集落刺激因子 (GM CSF)抗体及GM CSF的含量以及血清癌胚抗原 (CEA)和乳酸脱氢酶 (LDH)的水平 ,探讨PAP的血清学指标对发病机制、诊断及病情监测的意义。方法 采用间接酶联免疫吸附测定 (ELISA)法检测 17例PAP患者 [特发性PAP(I PAP) 16例 ,先天性 1例 ],18例其他肺部疾病患者 (疾病对照组 ) ,4 0名正常人 (健康对照组 )的血清中抗GM CSF抗体的水平。采用ELISA检测各血清标本中GM CSF及CEA的含量。采用速率法测定血清LDH水平。结果 I PAP组、疾病对照组及健康对照组血清中抗GM CSF抗体的吸光度 (A)值分别为 1 2 6 3± 0 0 4 7、0 835± 0 0 18和 0 2 4 6± 0 0 0 9。如果以健康对照组均值的 4倍为截断点 ,抗GM CSF抗体诊断I PAP的敏感性和特异性分别为 93 8%和 10 0 %。 18% (3/ 17)的PAP患者和 5 % (1/ 19)的疾病对照组血清中检测出GM CSF含量 ,余标本中GM CSF的含量均未检测出 (<0 7pg/ml)。I PAP患者血清LDH和CEA水平均较疾病对照组或健康对照组升高 (P <0 0 5 ) ,与肺泡气 动脉血氧分压差 [P(A a) O2 ]相关 (r分别为 0 76 9和 0 5 5 2 ) ,两者之间亦存在相关性 (r =0 5 18)。PAP患者LDH含量在灌洗治疗前 [(348 38± 38 88)U/L]、

Objective To evaluate the application of serum markers in the diagnosis,monitoring and understanding of the mechanisms of pulmonary alveolar proteinosis(PAP),the levels of the autoantibody against granulocyte macrophage colony stimulating factor(anti GM CSF antibody),granulocyte macrophage colony stimulating factor(GM CSF),and other serum markers,lactate dehydrogenase(LDH) and carcinoembryonic antigen(CEA),were measured in patients with PAP Methods Serum samples were taken from 17 PAP patients(16 idiopathic and 1 congenital PAP),18 patients with other pulmonary diseases(disease control) and 40 healthy volunteers(healthy control) Anti GM CSF antibody was measured with indirect enzyme linked immunosorbent assay(ELISA) GM CSF and CEA were measured with commercial ELISA kits LDH was measured with a kinetic method Results The absorbance at 450 nm of serum anti GM CSF antibody in the idiopathic PAP(I PAP),disease control and healthy control were 1 263±0 047,0 835±0 018 and 0 246±0 009 respectively The sensitivity and specificity of anti GM CSF in the diagnosis of I PAP were 93 8% and 100% respectively, if the cutpoint was set as 4 times the average value of the healthy control GM CSF was not detectable in most PAP and other samples except 3/17 of PAP and 1/19 of disease control The serum level of LDH was increased in I PAP patients and correlated with CEA ( r = 0 518) and alveolar artery oxygen gradient( r =0 769) CEA was increased in I PAP patients[(12 85±3 79) ng/ml] compared with disease control[(2 04±0 63) ng/ml] and health control[(1 46±0 34) ng/ml] and correlated with alveolar artery oxygen gradient( r =0 552) The LDH levels decreased after lavage therapy[(348 38±38 88),(242 88±30 71)U/L, P <0 05] Conclusions The high sensitivity and specificity of anti GM CSF antibody make it a potential diagnostic serum marker for I PAP LDH and CEA are useful markers in evaluation of disease progression of PAP