THE GENETICS OF CO-STIMULATION IN DIFFUSE (PRO-FIBROTIC) LUNG DISEASES

Despite exhaustive efforts, progress in gene mapping of fibrosing lung diseases has been very slow. In the last 15 or so years, our knowledge of the association of HLA alleles in SSc and sarcoidosis has improved, but the exact mechanism involved remains elusive. Results showed in this thesis indicate that in addition to the HLA, co-stimulatory molecules also play an important role in the pathogenesis of these disorders. There is also evidence that genes involved in trafficking of inflammatory cell to lung are also involved in pathogenesis of SSc and sarcoidosis. In the coming few years, accessory molecules, i.e. co-stimulatory molecules, innate immunity genes and trafficking molecules, are likely to play an even more important role and the acceleration in disease gene discovery will shed new light on the biological pathways involved in the pathogenesis of fibrosing lung diseases.