Long-term immune reconstitution in patients treated with autologous stem cell transplantation for refractory autoimmune diseases

Objectives

We performed here a detailed analysis of the newly developing immune systems in patients treated with immune ablation and subsequent autologous stem cell transplantation (ASCT) for severe autoimmune diseases.

Methods

Peripheral blood lymphocytes were analyzed using flow cytometry, including assessment of TCR-Vβ repertoire of Th cells. Thymic activity was determined by measuring T-cell receptor excision circles (TRECs) in distinct peripheral blood Th cell subsets by quantitative RT-PCR analysis.

Results

Twelve patients, with median follow up of 40 months, were included in the trial thus far: polychonditis (n = 1), systemic lupus erythematosus (SLE; n = 6), systemic sclerosis (SSc; n = 3), panniculitis (n = 1) and MS (n = 1). Clinical remission has been achieved in seven patients: polychondritis (n = 1), SLE (n = 5) and MS (n = 1). We observed progress of disease in patients with SSc and panniculitis. In one patient SLE reactivated 17 months after ASCT. In all responding patients no autoreactive Th cells could be detected, and serological remission has been achieved. Lymphocyte compartments reconstituted functionally in all patients as shown by the reappearance and persistence of naïve T cells with high levels of TRECs and restored diversity of the T cell receptor repertoire. Reconstituting B cells were found to be of naïve phenotype. Although we observed similar kinetics of lymphocyte repopulation in the nonresponding SSc patients, autoantibody titres (ANA, SCL70) were not affected by conditioning.

Conclusion

The newly generated immune system in responding patients is tolerant to rheumatic autoantigens and able to react to pathogens. We conclude that in successfully treated patients autoreactive memory and effector lymphocytes have been eliminated efficiently. Our data demonstrate that ASCT can induce stable long-term clinical and serological remission in patients with severe, standard-therapy refractory autoimmune diseases.