Genetic factors in scleroderma.
1. In no ethnic group is the overall association between SSc and the MHC, T-cell receptors, or drug metabolism phenotypes strong enough for direct clinical use. 2. Indications are that associations between specific subsets of SSc patients and genetic markers will assume greater importance both diagnostically and prognostically. The lung fibrosis group may be a prime candidate. 3. Genetic markers are useful means of relating chemically induced SSc-like disorders with the classical disease. Vinyl chloride disease is an example. 4. Evidence is emerging of strong associations between certain genetic markers and autoantibody production; a similar story has emerged in SLE. We believe that genetic testing will influence therapy in at least a subset of SSc patients, but that a dramatic breakthrough will not be made until we know how the genetics of the disease relate to the primary biochemical disease characteristic, that is the overproduction of collagen. In this respect, it has been suggested that the 5' flanking DNA of dermal collagen genes is particularly susceptible to the binding by Scl-70 (topoisomerase I). A problem is how to combine this and the other observations discussed above. Chromosomal instability can be linked to both the MHC and SSc-inducing chemicals, and the association of autoantibodies to topoisomerase I provides a tentative link between the MHC and collagen gene expression. Although the role and reason for anti-Scl 70 in SSc is unknown, humoral autoimmunity, at least in SLE, appears to be strongly dependent on specific HLA genes.
Briggs
D
D
Department of Molecular Immunogenetics, Guy's Hospital, London.
Black
C
C
Welsh
K
K
D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000276:immunology