Altered thymic CD4+ T-cell recovery after allogeneic hematopoietic stem cell transplantation is critical for nocardiosis.

PURPOSE OF THE STUDY: Nocardia affects immunocompromised human host exhibiting an altered cell-mediated immunity. Infectious risk after allogeneic hematopoietic cell transplantation (AHCT) is significantly correlated to the recovery status of donor-derived immune system, especially CD4+ T-cells reconstitution and thymopoiesis. The purpose of this paper is to highlight a lack of cell-mediated immunity recovery for patients presenting a nocardiosis compared to a control cohort. PATIENTS AND METHODS: This is a case control retrospective monocentric study. We retrospectively analyzed a monocentric cohort of 15 cases of nocardiosis after AHCT and we explored the degree of patients' immunosuppression by phenotyping circulating lymphoid subpopulations, including NK cells, CD8+ T-cells, CD4+ T-cells and CD19+ B-cells. We focused on CD4+ T-cell subsets to appreciate thymic output, especially on naive CD4+ T-cells (NTE, CD45RA+/RO- CD4+ T-cells) and recent thymic emigrants (RTE, CD4+CD45RA+/RO-/CD31+). Infected patients were paired with a control cohort of patients with identical transplantation characteristics screened on hematological disease, AHCT conditioning, primary graft-versus-host disease (GHVD) prophylaxis, graft type, sex, age, and season at the AHCT and data concerning immunological reconstitution were compared. RESULTS: At onset of nocardiosis, circulating lymphocytes and CD4+ T-cells means count were respectively 730/µL and 162/µL. CD8+ T-cells, CD56+ NK cells and CD19+ B-cells means count were respectively 362/µL, 160/µL, 112/µL. CD4+ T-cells subpopulations, naïve CD4+ T-cells production was impaired with NTE and RTE means count at 26/µL and 11/µL respectively. Comparison between nocardiosis cohort and control cohort over time highlight significant lower cellular count for lymphocytes, CD4+ T-cells, NTE and RTE with p = 0.001, p < 0.001, p < 0.001, p < 0.001 respectively. CONCLUSION: Immune recovery monitoring follow-up after AHCT is of particular importance to identify patients susceptible to develop Nocardiosis. Efficient microbiological investigations toward Nocardia such PCR should be used in case of compatible clinical presentation.