SEX-DEPENDENCY AND AGE-DEPENDENCY OF IGG AUTOANTIBODIES AGAINST IL-1-ALPHA IN HEALTHY HUMANS

Naturally occurring anti-interleukin (IL)-1 alpha IgG antibodies (Ab-I L-1 alpha) were measured in sera of 466 healthy Danish blood donors. A b-IL-1 alpha bound IL-1 alpha with exceptionally high affinity (Kd: 10 (-11) M) and neutralized both cell-associated and extracellular IL-1 a lpha but not IL-1 beta or IL-1 receptor antagonist. More than 80% of t he saturable binding of rIL-1 alpha to serum was to Ab-IL-1 alpha, sug gesting that these antibodies are the quantitatively most important IL -1 alpha-binding components in serum. Judged by second antibody precip itation 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 p ositive than women (P<0.001), there were no sex- or age-dependent alte rations in the average affinities of the antibodies. Free IL-1 alpha-l ike molecules were generally not detected in these sera. However, acid treatment showed that 25% of Ab-IL-1 alpha-positive sera contained lo w amounts of IL-1 alpha-Ab-IL-1 alpha immune complexes. IgG4 represent ed the main IgG isotype, whereas IgC3 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 n ormal 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.