Hansen M B, Svenson M, Abell K, Varming K, Nielsen H P, Bertelsen A, Bendtzen K
Department of Infectious Diseases M, Righospitalet, University Hospital, Copenhagen, Denmark.
Eur J Clin Invest. 1994 Mar;24(3):212-8. doi: 10.1111/j.1365-2362.1994.tb00991.x.
Naturally occurring anti-interleukin (IL)-1 alpha IgG antibodies (Ab-IL-1 alpha) were measured in sera of 466 healthy Danish blood donors. Ab-IL-1 alpha bound IL-1 alpha with exceptionally high affinity (Kd: 10(-11) M) and neutralized both cell-associated and extracellular IL-1 alpha but not IL-1 beta or IL-1 receptor antagonist. More than 80% of the saturable binding of rIL-1 alpha to serum was to Ab-IL-1 alpha, suggesting that these antibodies are the quantitatively most important IL-1 alpha-binding components in serum. Judged by second antibody precipitation assay, the prevalence of Ab-IL-1 alpha varied between 30% and 75% and correlated positively with age (P = 0.037). The binding capacity of serum also increased with age. Although men were more frequently positive than women (P < 0.001), there were no sex- or age-dependent alterations in the average affinities of the antibodies. Free IL-1 alpha-like molecules were generally not detected in these sera. However, acid treatment showed that 25% of Ab-IL-1 alpha-positive sera contained low amounts of IL-1 alpha-Ab-IL-1 alpha immune complexes. IgG4 represented the main IgG isotype, whereas IgG3 Ab-IL-1 alpha were undetectable. The relative amounts of IgG4 Ab-IL-1 alpha increased while IgG2-and IgG1 Ab-IL-1 alpha decreased in elderly individuals. The presence in normal individuals and the lack of affinity maturation with age suggest that Ab-IL-1 alpha may be regulatory natural auto-antibodies perhaps coded by germline genes.
在466名丹麦健康献血者的血清中检测了天然存在的抗白细胞介素（IL）-1α IgG抗体（Ab-IL-1α）。Ab-IL-1α以极高的亲和力（解离常数Kd：10⁻¹¹ M）结合IL-1α，可中和细胞相关及细胞外的IL-1α，但不能中和IL-1β或IL-1受体拮抗剂。重组人IL-1α（rIL-1α）与血清的可饱和结合中，超过80%是与Ab-IL-1α结合，这表明这些抗体是血清中数量上最重要的IL-1α结合成分。通过二抗沉淀试验判断，Ab-IL-1α的阳性率在30%至75%之间，且与年龄呈正相关（P = 0.037）。血清的结合能力也随年龄增加。虽然男性阳性率高于女性（P < 0.001），但抗体的平均亲和力没有性别或年龄依赖性改变。这些血清中一般未检测到游离的IL-1α样分子。然而，酸处理显示25%的Ab-IL-1α阳性血清含有少量IL-1α-Ab-IL-1α免疫复合物。IgG4是主要的IgG亚型，但未检测到IgG⁃3 Ab-IL-1α。在老年人中，IgG4 Ab-IL-1α的相对含量增加，而IgG2和IgG1 Ab-IL-1α减少。正常个体中存在Ab-IL-1α且其亲和力不随年龄成熟，这表明Ab-IL-1α可能是由种系基因编码的调节性天然自身抗体。
