THE COLLAGEN DISEASES 



portion of cases of lupoid hepatitis, continuing damage to 

 hepatic cells is indicated by a high level of glutamic-oxalo- 

 acetic transaminase in the serum. O'Brien, Goble and 

 Mackay (1958) have recently shown that this level can be 

 strikingly reduced by treatment of the patient with adequate 

 doses of cortisone. The obvious interpretation is that the 

 cortisone has diminished or annulled the damaging effect of 

 antigen-antibody reaction (or its equivalent) in the im- 

 mediate proximity of the liver cells. 



It appears that the antigenic determinants involved are 

 released most freely from damaged tissue. This will hold, 

 irrespective of whether, like the thyroglobulin in Hashimoto's 

 disease, the liver antigen is of a type that is normally in- 

 accessible and hence treated as foreign, or whether the mesen- 

 chymal cells represent mutant clones of forbidden specificity. 

 In the second case, some breakdown in normal homeostasis 

 may have to be postulated. A possible suggestion is that 

 when a forbidden mutant appears corresponding to an anti- 

 genic determinant of an easily accessible body component, 

 the forbidden clone is rapidly eliminated. When, however, 

 the mutant corresponds to some rarer pattern not readily 

 accessible except in inflamed or traumatized organs, the 

 possibility of a vicious circle arises, presumably most readily 

 when the organism is under stress. Cortisone can break the 

 vicious circle. 



The possibility that the establishment of one clone of 

 such tissue-pathogenic lymphocytes may provide a basis on 

 which other clones with different tissue specificity are more 

 likely to arise, may have some bearing on the multiplicity 

 of manifestations which can be observed in some cases of 

 collagen disease. 



There are many other rare conditions which have one or 

 more of the characters that one would associate with the 

 production of forbidden clones of mesenchymal cells. One 

 of these is the complex of conditions in children typified by 

 Letterer-Siwe disease. This condition is characterized by 



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