IMMUNOPRINTING REVEALS DIFFERENT GENETIC BASES FOR (AUTO)IMMUNE DISEASES

The genetic basis of complex (auto)immune diseases has been studied fo r an ovine nematode infection, human rheumatoid arthritis (RA), early onset pauciarticular arthritis (EOPA) and multiple sclerosis (MS). Imm unoprinting combines the powerful simplicity of polymerase chain react ion (PCR)-based amplification of discrete, highly informative microsat ellite loci with the principle of genetic associations. This approach has allowed us to define novel genetic risk factors in adult RA patien t categories whereas EOPA forms in juveniles display other prominent g enetic contributions. Differentially regulated tumor necrosis factor ( TNF) expression may lead to a better understanding of the causal patho genesis of EOPA while T cell receptor (TCR) gene polymorphisms appear crucial for RA manifestation in certain patient groups. Statistically significant marker associations have still to be defined for MS in lar ger panels of patient and control cohorts. The clinical course of the disease will probably have to be taken into account when associations with lymphokine levels are evaluated. In essence a convoluted myriad o f negative and a few positive disease association data have been gener ated efficiently by immunoprinting. As expected, the interrelationship s are truly complicated between the polymorphic genetic instances pred isposing to autoimmune disease. Nevertheless, risk factors may be defi ned on an individualized basis by indirect gene diagnosis revealing pr edispositions and providing a more solid basis for differential diagno sis and treatment.