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

Curr Res Transl Med. 2019 Nov;67(4):135-143. doi: 10.1016/j.retram.2019.05.001. Epub 2019 Jun 1.

Abstract

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.

Keywords: Allogeneic hematopoietic stem cell transplant; Immune recovery; Nocardia; Opportunistic infection; Thymic CD4(+)T-cell.

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology*
  • Case-Control Studies
  • Female
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / therapy*
  • Hematopoiesis / physiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Immune Reconstitution / physiology*
  • Immunity, Cellular / physiology
  • Immunocompromised Host
  • Male
  • Middle Aged
  • Nocardia Infections / etiology*
  • Nocardia Infections / immunology*
  • Opportunistic Infections / etiology
  • Opportunistic Infections / immunology
  • Retrospective Studies
  • Risk Factors
  • Thymus Gland / immunology*
  • Thymus Gland / pathology
  • Transplantation Conditioning / adverse effects
  • Transplantation, Homologous