Letter: Frequency of cystic-fibrosis gene.

Mr Stuart and Dr Burdon speculate on the possibility that the high 
frequency of the cystic-fibrosis gene among Caucasians may be due to 
the heterozygotes having some advantage in biological fitness over normal homozygotes. 
They suggest that this might be due to increased resistance to 
typhus, once endemic in Europe, on the basis of the well-known 
immunological cross-reactivity between the causative organism, Rickettsia prowazeki, and certain strains 
of the species Proteus vulgaris, which is agglutinated by sera from 
cystic-fibrosis patients and heterozygotes. However, there is no evidence that this 
agglutination is an immunological reaction. It appears microscopically to be associated 
with disorganisation and inhibition of the bacterial flagellae leading to clumping 
of the organisms. As such it is probably analogous to the 
effect on cilia of rabbit trachea and oyster or mussel gills. 
The cilia factor, although associated with IgG, is now known not 
to be IgG itself and may well be the C3a component 
of complement. These and other observations, such as those on salivary 
and sweat gland secretions and on sodium flux, suggest that all 
these phenomena are membrane rather than immunological effects. Although it is 
possible that a Proteus flagella antigen could also be the binding 
site for the cilia factor, this seems improbable. An alternative hypothesis 
is that heterozygotes for the cystic-fibrosis gene have increased resistance to 
tuberculosis. This would meet the requirement of a common disease recently 
endemic in Europe at least as well as typhus, and is 
suggested by indirect evidence from a family study demonstrating a significantly 
lower incidence of tuberculosis among the parents of cystic-fibrosis patients than 
among parents of controls. 