Sex‐ and age‐dependency of IgG auto‐antibodies against IL‐1α in healthy humans

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Abstract
Naturally occurring anti‐interleukin (IL)‐1α IgG antibodies (Ab‐IL‐1α) were measured in sera of 466 healthy Danish blood donors. Ab‐IL‐1α bound IL‐1α with exceptionally high affinity (Kd: 10‐11 M) and neutralized both cell‐associated and extracellular IL‐1α but not IL‐1β or IL‐1 receptor antagonist. More than 80% of the saturable binding of rIL‐1α to serum was to Ab‐IL‐1α, suggesting that these antibodies are the quantitatively most important IL‐1α‐binding components in serum. Judged by second antibody precipitation assay, the prevalence of Ab‐IL‐1α 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‐1α‐like molecules were generally not detected in these sera. However, acid treatment showed that 25% of Ab‐IL‐1α‐positive sera contained low amounts of IL‐1α‐Ab‐IL‐1α immune complexes. IgG4 represented the main IgG isotype, whereas IgG3 Ab‐IL‐1α were undetectable. The relative amounts of IgG4 Ab‐IL‐1α increased while IgG2‐and IgG1 Ab‐IL‐1α decreased in elderly individuals. The presence in normal individuals and the lack of affinity maturation with age suggest that Ab‐IL‐1α may be regulatory natural auto‐antibodies perhaps coded by germline genes.