Wilkes D S, Heidler K M, Niemeier M, Schwenk G R, Mathur P N, Breite W M, Cummings O W, Weissler J C
Indiana University School of Medicine, Department of Medicine, Indianapolis, 46202, USA.
J Investig Med. 1994 Dec;42(4):652-9.
Lung allograft rejection (AR) is thought to involve T-helper-1 (Th-1) lymphocytes mediating both cellular immunity and alloantibody production. Th-1 lymphocytes produce gamma interferon (gamma IFN) and induce IgG2 production, suggesting that increased IgG2 production might occur during AR. The purpose of this study was to determine if locally altered bronchoalveolar IgG2/IgG1 ratios might correlate with AR.
Eighteen recipients of lung allografts underwent a total of 25 bronchoscopies for surveillance or at times of suspected infection or AR. Bronchoalveolar lavage (BAL), serum collection, and transbronchial biopsy (TB) were performed on all patients. gamma IFN, IgG1, IgG2 levels, and the ratio of IgG2/IgG1 were determined in serum and BAL and matched with TB histology. Five nonsmoking normal volunteers undergoing bronchoscopy, BAL, and serum collection served as controls.
IgG2 was upregulated in allograft BAL during AR as determined by the ratio IgG2/IgG1 (2.91 +/- 0.79 SEM vs 0.62 +/- SEM, p < 0.019, IgG2/IgG1, AR BAL vs non-AR BAL, respectively). An IgG2/IgG1 > or = 1 in allograft BAL (95% confidence intervals 1.26 to 4.56) was 80% specific and 91% sensitive for the diagnosis of AR with a positive predictive value of 92%. A BAL IgG2/IgG1 < 1 (95% confidence interval 0.27 to 0.97) had a negative predictive value of 77%. After therapy in two patients the elevated IgG2/IgG1 ratio reversed to normal (ie, < 1) with histologic resolution of AR.
Human lung AR is associated with a locally increased IgG2/IgG1 ratio suggesting locally upregulated Th-1 lymphocyte activity during lung AR.
肺移植排斥反应(AR)被认为涉及介导细胞免疫和同种异体抗体产生的辅助性T细胞1(Th-1)淋巴细胞。Th-1淋巴细胞产生γ干扰素(γ干扰素)并诱导IgG2产生,这表明在AR期间可能会出现IgG2产生增加。本研究的目的是确定局部改变的支气管肺泡IgG2/IgG1比值是否与AR相关。
18例肺移植受者共接受了25次支气管镜检查,用于监测或在怀疑感染或AR时进行。对所有患者进行支气管肺泡灌洗(BAL)、血清采集和经支气管活检(TB)。测定血清和BAL中的γ干扰素、IgG1、IgG2水平以及IgG2/IgG1比值,并与TB组织学结果进行匹配。5名接受支气管镜检查、BAL和血清采集的非吸烟正常志愿者作为对照。
通过IgG2/IgG1比值测定,在AR期间同种异体移植BAL中IgG2上调(分别为2.91±0.79 SEM对0.62±SEM,p < 0.019,IgG2/IgG1,AR BAL对非AR BAL)。同种异体移植BAL中IgG2/IgG1>或=1(95%置信区间1.26至4.56)对AR诊断的特异性为80%,敏感性为91%,阳性预测值为92%。BAL IgG2/IgG1<1(95%置信区间0.27至0.97)的阴性预测值为77%。两名患者治疗后,升高的IgG2/IgG1比值恢复正常(即<1),AR组织学消退。
人类肺AR与局部IgG2/IgG1比值增加相关,提示肺AR期间局部Th-1淋巴细胞活性上调。