Analysis of immune reconstitution after autologous bone marrow transplantation in systemic sclerosis

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Abstract
Objective: To analyze hematopoietic and immune reconstitution after autologous hematopoietic stem cell transplantation (HSCT) in 7 patients with systemic sclerosis (SSc).Methods: Two groups of patients were retrospectively constituted according to whether they had a favorable clinical response (group A; n = 4) or no response or a relapse of disease (group B; n = 3) after HSCT. Immune reconstitution was analyzed every 3 months using lymphocyte immunophenotyping, α/β T cell receptor (TCR) diversity analysis, and ex vivo thymic function analysis by quantification of TCR rearrangement excision circles (TRECs).Results: Patients had similar characteristics at study entry, except for a lower modified Rodnan skin thickness score (P = 0.03) and a lower Health Assessment Questionnaire score (P = 0.05) in group A than in group B. The number of reinjected cells and the time to hematopoietic reconstitution were similar in both groups. The absolute numbers of CD19+ and CD20+ B cells were lower in group A than in normal controls (P < 0.05) and within the normal range in group B. Absolute numbers of T and natural killer lymphocytes were normal before HSCT. Numbers of CD3+ cells remained low thereafter. Numbers of CD8+ cells were back to normal 3 months after HSCT in both groups. B cell counts were low until 6 months after HSCT in group A and stayed in the normal range in group B. The CD3+ defect was sustained in group A, with an opposite trend and a faster CD4+ reconstitution profile in group B. The T cell repertoire was skewed before and until 1 year after HSCT, with shared expansions before and after transplant in a given individual. TREC values correlated negatively with C‐reactive protein levels (rs = −0.41, P = 0.001) and positively with CD19+ (rs = 0.35, P = 0.001) and CD20+ (rs = 0.34, P = 0.002) lymphocyte counts.Conclusion: B and T lymphocyte populations remained disturbed for at least 1 year after HSCT in SSc patients, which may reflect the persistence of an underlying disease mechanism.