Morse J H, Barst R J, Fotino M, Zhang Y, Flaster E, Fritzler M J
Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Clin Exp Immunol. 1996 Nov;106(2):389-95. doi: 10.1046/j.1365-2249.1996.d01-848.x.
HLA class II alleles (DNA typing) and antibodies to HMG-1,2,14,17 proteins and H1 histone were determined in three predominantly Caucasian groups of patients with pulmonary hypertension (PHT). Forty-four adults had primary pulmonary hypertension (PPH), 42 children had PPH, and 41 children had PHT associated with anatomically large congenital pulmonary to systemic shunts (PHT + shunt). The HLA class II alleles in the Caucasian patients were compared with those of 51 healthy Caucasian controls. Eight (18%) of 44 sera from adults with PPH bound HMG-14 and 23 (52%) bound H1. None of 42 sera from children with PPH bound either HMG-14/17 or HMG-1/2, whereas four (10%) bound H1. In the PHT + shunt group of 41 children, two (5%) bound HMG-14, one (3%) bound HMG-17, four (10%) bound HMG-1 and/or HMG-2, and six (15%) bound H1. Among the 12 HMG antibody-positive patients, HLA-DQ6 was present in nine of 10 HLA typed patients (six PPH adults and three PHT + shunt children), seven of whom had antibodies to HMG-14 and one to HMG-17. The 100% frequency of HLA-DQ6 in seven Caucasian patients with antibodies to HMG-14/17 was statistically significant when compared with the 41% frequency of -DQ6 present in 51 healthy Caucasian controls (pc = 0.027, pc = Bonferroni correction, OR = 21.3). In contrast, when compared with controls, 25 patients with PPH and anti-H1 antibodies (21 adults and four children) had increased frequencies of HLA-DQ7 and -DR5 (60% versus 29%, P = 0.010, OR = 3.6 and 48% versus 22%, P = 0.018, OR = 3.4), which were not significant after correction. In essence, antibodies to HMG-14 and to H1 proteins were present predominantly in adults with PPH, suggesting that the pattern of response to HMG-14/17 was similar to that previously reported in systemic lupus erythematosus (SLE) and drug-induced autoimmunity. This is the first report of an association between autoantibodies directed against HMG and H1 with immunogenetic markers. These data suggest that a subset of patients with PPH may have an autoimmune disease.
在三个主要为白种人的肺动脉高压（PHT）患者组中，测定了HLA II类等位基因（DNA分型）以及针对高迁移率族蛋白（HMG）-1、2、14、17和H1组蛋白的抗体。44名成年患者患有原发性肺动脉高压（PPH），42名儿童患有PPH，41名儿童患有与解剖学上大的先天性肺到体循环分流相关的PHT（PHT +分流）。将白种人患者的HLA II类等位基因与51名健康白种人对照的进行比较。44名成年PPH患者的血清中有8份（18%）与HMG - 14结合，23份（52%）与H1结合。42名儿童PPH患者的血清中没有一份与HMG - 14/17或HMG - 1/2结合，而有4份（10%）与H1结合。在41名儿童的PHT +分流组中，2份（5%）与HMG - 14结合，1份（3%）与HMG - 17结合，4份（10%）与HMG - 1和/或HMG - 2结合，6份（15%）与H1结合。在12名HMG抗体阳性患者中，10名进行了HLA分型的患者中有9名存在HLA - DQ6（6名成年PPH患者和3名PHT +分流儿童），其中7名有针对HMG - 14的抗体，1名有针对HMG - 17的抗体。与51名健康白种人对照中存在的HLA - DQ6的41%频率相比，7名对白种人HMG - 14/17有抗体的患者中HLA - DQ6的100%频率具有统计学意义（pc = 0.027，pc = Bonferroni校正，OR = 21.3）。相比之下，与对照相比，25名有抗H1抗体的PPH患者（21名成年人和4名儿童）的HLA - DQ7和 - DR5频率增加（分别为60%对29%，P = 0.010，OR = 3.6和48%对22%，P = 0.018，OR = 3.4），校正后无统计学意义。本质上，针对HMG - 14和H1蛋白的抗体主要存在于成年PPH患者中，这表明对HMG - 14/17的反应模式与先前在系统性红斑狼疮（SLE）和药物诱导的自身免疫中报道的相似。这是关于针对HMG和H1的自身抗体与免疫遗传标记之间关联的首次报告。这些数据表明，一部分PPH患者可能患有自身免疫性疾病。
