Garred P, Madsen H O, Petersen J, Marquart H, Hansen T M, Freiesleben Sørensen S, Volck B, Svejgaard A, Andersen V
Department of Clinical Immunology, The National University Hospital (Rigshospitalet), Copenhagen, Denmark.
J Rheumatol. 1998 Aug;25(8):1462-5.
Some chemokine receptors have been shown to be co-receptors for human immunodeficiency virus (HIV-1). A 32 base pair deletion allele in the CC chemokine receptor 5 gene (CCR5 delta32 allele) affects both transmission of HIV-1 and acquired immunodeficiency syndrome (AIDS)-free survival. Chemokines are suggested to be critical for establishment of inflammatory processes in autoimmune diseases such as rheumatoid arthritis (RA). We hypothesized that the defective allele may modulate the inflammatory process in RA.
Using polymerase chain reaction methods, we investigated the significance of the CCR5 delta32 allele in 163 Danish patients with RA and monitored clinical and paraclinical variables.
The gene frequency of the CCR5 delta32 allele (0.10) did not deviate significantly from healthy controls and from that reported in healthy Caucasian populations, nor did the distribution deviate from the Hardy-Weinberg predictions (131 wild type, 30 heterozygous, 2 homozygous for the deletion allele; p = 0.85). However, a significantly increased proportion of those carrying the deletion allele were negative for IgM rheumatoid factor (RF) compared to those homozygous for the normal allele (29 vs 9%; p = 0.007). The proportion of CCR5 delta32 allele carriers with swollen joints was decreased compared to those homozygous for the normal allele (35 vs 58%, respectively; p = 0.03), as was the duration of morning stiffness (median 0 vs 60 min, respectively; p = 0.0002).
The CCR5 delta32 allele seems to have some influence on RA variables including RF, which suggests that inhibition of chemokine receptors might be a potential target for disease modifying therapy in RA.
一些趋化因子受体已被证明是人类免疫缺陷病毒（HIV-1）的共受体。CC趋化因子受体5基因中的一个32碱基对缺失等位基因（CCR5 delta32等位基因）会影响HIV-1的传播以及无获得性免疫缺陷综合征（AIDS）生存期。趋化因子被认为对类风湿关节炎（RA）等自身免疫性疾病中炎症过程的建立至关重要。我们推测该缺陷等位基因可能会调节RA中的炎症过程。
我们使用聚合酶链反应方法，研究了CCR5 delta32等位基因在163例丹麦RA患者中的意义，并监测了临床和辅助临床变量。
CCR5 delta32等位基因的基因频率（0.10）与健康对照以及健康白种人群中报道的频率无显著差异，其分布也未偏离哈迪-温伯格预测（131例野生型，30例杂合子，2例缺失等位基因纯合子；p = 0.85）。然而，与正常等位基因纯合子相比，携带缺失等位基因者中IgM类风湿因子（RF）阴性的比例显著增加（分别为29%和9%；p = 0.007）。与正常等位基因纯合子相比，CCR5 delta32等位基因携带者关节肿胀的比例降低（分别为35%和58%；p = 0.03），晨僵持续时间也降低（中位数分别为0分钟和60分钟；p = 0.0002）。
CCR5 delta32等位基因似乎对包括RF在内的RA变量有一定影响，这表明抑制趋化因子受体可能是RA疾病改善治疗的一个潜在靶点。
