Juvenile dermatomyositis (JDMS) is a systemic disorder characterized by an inflammatory myopathy and vasculitis. The pathogenesis of JDMS is hypothesized to be an autoimmune process which is induced by a viral illness in a genetically susceptible individual. We have demonstrated genetic susceptibility in JDMS by identifying an increased frequency of the major histocompatibility complex (MHC) class II antigen HLA- DQA1*0501. This information, my research interest and experience as well as the ability to obtain subjects with this unusual and yet homogenous autoimmune process allows the ideal environment to pursue the questions below. The identification of the HLA-DQA1*0501 allele as a susceptibility gene, allows us to determine the functional significance of this molecule with respect to peptide binding and T- cell receptor (TCR) interactions. Structural analysis has begun with nucleotide sequencing of the HLA- DQA1*0501 gene. Functional analysis can be determined by creating a panel of (APC) lines that display class II molecules with allelic variations, evaluation of these APC lines' alloreactive T cells and in the presentation of antigenic peptides. By having the ability to investigate a group of patients who have a homogeneous autoimmune process with a recognized increase in a specific HLA antigen, suggested to be the susceptibility allele, we have an ideal study population from which we can effectively study a susceptibility gene; in structure (by determining the HLA-DQA1*0501 sequence); and function (by determining the restriction elements used by antigen specific T cells in relationship to the HLA-DQA1*0501 allele and by determining differences in the T cell response of JDMS and controls in response to allelic variations). This investigation under the guidance of Dr Frelinger, who not only has the facilities but also the expertise in the area of HLA structure and function, gives the ideal environment for which to successfully become an independent investigator while addressing an important immunologic related autoimmune disease question.
| West, J E; Reed, A M (1999) Analysis of HLA-DM polymorphism in juvenile dermatomyositis (JDM) patients. Hum Immunol 60:255-8 |
| Reed, A M; Collins, E J; Shock, L P et al. (1997) Diminished class II-associated Ii peptide binding to the juvenile dermatomyositis HLA-DQ alpha 1*0501/DQ beta 1*0301 molecule. J Immunol 159:6260-5 |
| Reed, A M; Stirling, J D (1995) Association of the HLA-DQA1*0501 allele in multiple racial groups with juvenile dermatomyositis. Hum Immunol 44:131-5 |
