[Diathesis and predisposition. A molecular reappraisal of the mode of reacting]

The identification of the causes of important infectious and hereditary diseases became scientifically clear in the last years of the nineteenth century and in the first years of the twentieth. Through many centuries, the lack of etiologic knowledge regarding diseases has extraordinarily enhanced the value of the concept of predisposition so that "diathesis" helped to "explain" many forms of morbidity. Several discoveries as to the real "causes" of diseases, however, led to a critical downgrading of its value. But in-depth knowledge regarding the proteins controlled by genes of the "major histocompatibility complex" (MHC, HLA) in man was followed, a few years later, by the demonstration of the fact that carriers of particular alleles are exposed to higher risks of contracting certain diseases than non-carriers of these molecules. A new key for interpretation-this time, a genetic and molecular one-was thus offered for the concept of "predisposition". Actually, man's HLA-associated molecular individuality induces and causes an extraordinarily personal way of reacting to various stimuli. An obvious consequence of this is not only that man, having become aware of his "molecular uniqueness" (which is significantly HLA-related), can view himself as a "biological Ego" but, most of all, that some of his predispositions towards becoming ill may be ascribed to some of his individual molecular characterizations. Thus, the onset and the course of many diseases would be viewed as the effect of a given "way of reacting". This could be recognized as the true essence of diathesis, 18 centuries after Galen.