[Clinical and immunological effects of leukapheresis therapy using cotton-wool filter for patients with rheumatoid
1Second Department of Internal Medicine, Hiroshima University School of Medicine.
Abstract:
Remarkable clinical effectiveness of leukapheresis (LP) using a cotton-wool filter as a therapy for patients with rheumatoid arthritis (RA) was previously reported. To study the mechanism and indications for this therapy, 14 patients with RA were treated with this filter 6 times at 2 weeks intervals. The effects on clinical symptoms and subpopulations of peripheral blood mononuclear cells were evaluated on day 0, 3, 7, 14, 42 and 84. The Ritchie articular index, swollen joint counts, Lansbury index and health assessment questionnaire (HAQ), all showed improvements within the first week and the improvements were still observed 3 month later. Improvements in tender joint counts and visual analog pain scale (VAPS) were also observed on day 84. Eight patients showed remarkable improvements (responders) and 6 showed no apparent improvement (non-responders) according to the ACR core set criteria. Responders showed several characteristic features compared to non-responders as follows: the duration of RA was significantly shorter, the anatomical stage was earlier, the positive rate of susceptible HLA-DR4 haplotype associated with Japanese RA (DRB1*0405) was lower, and the proportion of CD4 + Leu8 + lymphocytes and the ratio of CD4+ cells to CD8+ cells (CD+/CD8 ratio) in the peripheral blood were higher throughout the treatment period and increased further even after the course of therapy. The proportion of CD4 + Leu8 + cells was inversely correlated with HAQ and VAPS, suggested that it is critically involved in the mechanism of this therapy. Blood leukocyte analysis at inlet and outlet of the filter showed increase of CD4 +, CD4 + Leu8 + cell percentages and CD4/CD8 ratio. These results suggested that patients with a shorter disease duration, less destruction of the joint, and without susceptible genes were more responsive to this therapy and that the mechanism of clinical improvement of RA by LP with cotton-wool involves immunological modification, such as immunosuppression by CD4 + Leu8 + lymphocytes.
