Predominance of autoimmune and rheumatic diseases in females

This paper offers an explanation for the higher female incidence found in many of the autoimmune and rheumatic diseases. A list of these diseases (Table 1) shows that half of them occur in three females for each male affected. Females are genetic and hence antigenic mosaics, half their somatic cells expressing antigens derived from the paternal X, half from the maternal X (female heterochromatinization). The Burnet-Jerne theory of somatic generation of antibody diversity and forbidden clone elimination states that lymphocytes under maturation in the thymus are killed or suppressed if they recognize and hence react to a histocompatibility antigen. If this were to hold for other self antigens as well, as recent models of clonal generation and selection mechanisms predict, then lymphocytes happening to pass the crucial stage in the thymus meeting only cells expressing one of the parental X's could be released still able to react to self i.e. those somatic cells expressing the other parental X with which the lymphocyte had not been in contact. Thus, self-tolerance would be more easily broken in females than in males.