Our previous findings show that TLI is an effective treatment modality in inducing long-term remissions in the """"""""lupus-like"""""""" glomerulonephritis of NZB/NZW and MRL/I mice even in the presence of advanced disease. The improvement in both renal and extra-renal manifestations of lupus in four patients treated with TLI suggests that radiotherapy may be an effective therapeutic modality in human nephritis. In all four cases, improvement began shortly after radiotherapy and persisted during the observation period of nearly two years. The proposed study has three main goals. The first is to enlarge the number of patients treated with TLI and observe the length of time of improvement and side effects during a three to five year observation period. The value of TLI as a treatment modality is critically dependent on the longevity of improvement and the lack of late side effects in this chronic disease. Thus, the study would be highly significant if the improvement persisted for as long as five years in the absence of late side effects. Enthusiasm would be dampened if the disease activity relapsed after two years, or serious radiation complications appeared after that time. The second main goal is to determine how long the marked immunological alterations (reduction in the in vitro function and number of helper T cells, reduction in in vitro immunoglobulin synthesis of peripheral blood lymphocytes, change in suppressor/helper T cell ratios) induced in the lupus patients persist, and whether these alterations correlate with disease activity over a long period of time. Correlations of this nature may provide insight into the immune basis of the disease and pathogenetic mechanisms. The third main goal is to directly compare the changes (and the time course of the changes) in the immune parameters, renal function, and feasibility of steroid reductions in two small group (7 each) of steroid unresponsive patients treated with either TLI or azathioprine. This study will allow us to determine whether a large controlled, randomized, prospective collaborative study of the comparison of TLI and cytotoxic drugs in lupus nephritis should be carried out at several medical centers.
| Myers, B D; Chagnac, A; Golbetz, H et al. (1991) Extent of glomerular injury in active and resolving lupus nephritis: a theoretical analysis. Am J Physiol 260:F717-27 |
| Chagnac, A; Kiberd, B A; Farinas, M C et al. (1989) Outcome of the acute glomerular injury in proliferative lupus nephritis. J Clin Invest 84:922-30 |
| Solovera, J J; Farinas, M C; Strober, S (1988) Changes in B lymphocyte function in rheumatoid arthritis and lupus nephritis after total lymphoid irradiation. Arthritis Rheum 31:1481-91 |
