The iceberg analogy of autoimmunity.

IMPORTANT contributions to the understanding of autoimmune processes have come from studies on populations (Serafini, Torrigiani & Masala, 1964; Jacobs et aL, 1969; Whittingham et al., 1969a; Couchman, Wigley & Prior, 1970; Hooper et al., 1971) which have shown a substantial proportion of subjects, usually elderly, with serological stigmata of autoimmunity. The iceberg analogy of autoimmunity is applicable in this context in that what is seen above the surface of the sea is only a small part of the total mass of the iceberg, corresponding to that relatively small number ofpatients with symptomatic autoimmune disease in the entire population. In the figure the iceberg represents the total population. The man in the boat is the clinician who sees as the top of the iceberg those patients with symptomatic autoimmune disease (clin AID) to which he ascribes a clinical diagnosis. The snorkeldiver is the histopathologist who, by viewing the iceberg from the surface or by making a shallow dive below the surface sees the same diseases as the clinician and, in addition, histologically evident but clinically insignificant autoimmune lesions (subclin AID). These are the mild non-destructive, focal inflammatory changes of gastritis, thyroiditis and sialadenitis seen in random histological surveys of tissues available by biopsy (Edwards & Coghill, 1966) or at necropsy (Waterhouse & Doniach, 1966; Bastenie et al., 1967). The aqualung diver is the serologist who by diving deeper below the surface sees serological evidence of autoimmunity (serolog AID) in an even larger proportion of the population with and without symptomatic autoimmune disease; the results of the population surveys indicate that this is a substantial portion of the iceberg. The 'unseen', the lowest portion of the iceberg, represents that remaining segment of the population, mostly young and mostly healthy, in whom stigmata of autoimmunity have not as yet appeared or will never appear. The sun beating down on the exposed top of the iceberg causes it to melt, and this in our analogy represents the various environmental agents which