Reconstitution of immunity after autologous CD34 cell transplantation for autoimmune diseases

To study immune reconstitution in patients recovering from extreme lymphopenia. Fifty-six patients with autoimmune diseases (systemic sclerosis or multiple sclerosis) were conditioned with total body irradiation, cyclophosphamide and anti-thymocyte globulin and received autologous CD34 cells. On day 7, circulating T and B cells were undetectable, and NK cell, monocyte and granulocyte counts were low. NK cell, monocyte and granulocyte counts recovered to normal by day 30, B cell counts by 6 months and CD8 T cell counts by 2 years. CD4 T cell counts were still low at 2 years (median 388/microliter). In the first 3 months T cells recovered primarily through peripheral expansion, whereas de novo generation predominated thereafter (Ki67 and TREC analysis). Serum levels of total IgM, IgA, IgG and IgG2 remained normal throughout the 2 years of follow up. Also, levels of antibodies for tetanus, H.influenzae, S.pneumoniae and Scl-70 (in Scl-70-seropositive patients pretransplant) did not change substantially. A total of 23 infections, excluding presumed respiratory tract infection or gastroenteritis, occurred between day 0 and 15, 25 infections between day 16 and 180, 9 infections between day 181 and 365, and 9 infections between day 366 and 730. After severe lymphopenia in adults, CD4 T lymphopenia persists for more than 2 years, and appears to be mildly clinically significant. The minimal change of levels of antibodies, including autoantibodies, suggests that autoimmune diseases caused by autoantibodies may not be improved by autologous transplantation.