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. 2024 Nov 25:15:1478777.
doi: 10.3389/fimmu.2024.1478777. eCollection 2024.

Thymic hyperplasia after autologous hematopoietic stem cell transplantation in multiple sclerosis: a case series

Alice Mariottini  1   2 , Riccardo Boncompagni  3 , Diletta Cozzi  4 , Edoardo Simonetti  3 , Anna Maria Repice  2 , Valentina Damato  1   2 , Mirella Giordano  3 , Vittorio Miele  4 , Chiara Nozzoli  3 , Luca Massacesi  1   2
Affiliations

Thymic hyperplasia after autologous hematopoietic stem cell transplantation in multiple sclerosis: a case series

Alice Mariottini et al. Front Immunol. .

Abstract

Introduction: Reactivation of thymopoiesis in adult patients with autoimmune disorders treated with autologous haematopoietic stem cell transplantation (AHSCT) is supported by studies exploring immunoreconstitution. Radiological evidence of thymic hyperplasia after AHSCT was previously reported in patients with systemic sclerosis, but, to our knowledge, it has not been described in multiple sclerosis (MS), where premature thymic involution has been observed and immunosenescence might be accelerated by disease-modifying treatments (DMTs).

Participants and methods: monocentric case series including MS patients who performed a chest CT scan for clinical purposes after having received AHSCT (BEAM/ATG regimen) for aggressive MS failing DMTs. Chest CT exams were reviewed by a thoracic radiologist: thymic hyperplasia was defined as a rounded mass in the thymic loggia with a density around 40 Hounsfield Units (HU) and thickness >1.3 cm.

Results: Fifteen MS patients were included; the median time interval between AHSCT and chest CT scan was 2 (range 1-18) months. All the patients were free from new inflammatory events and DMTs over a median follow-up of 36 months (range 12-84) after AHSCT. Thymic hyperplasia was detected in 3/15 (20%) cases in an exam taken 1 to 3 months after AHSCT; all these patients were females, and aged 30 to 40 years. Lung infections and secondary autoimmunity were diagnosed in 5 and 1 cases, respectively, none of which showed thymic hyperplasia. No associations between thymic hyperplasia and clinical-demographic characteristics or post-AHSCT outcomes were observed.

Conclusions: Thymic hyperplasia was detected in 20% of MS patients recently treated with AHSCT. These results are consistent with previous immunological studies showing that AHSCT promotes thymus reactivation in MS patients, further supporting de-novo thymopoiesis as a cornerstone of immune reconstitution after AHSCT in this population.

Keywords: CT; autoimmune diseases; hematopoietic stem cell transplantation; imaging; immune reconstitution; multiple sclerosis; thymus; transplant.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Author Contributions The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Mechanisms of immunoreconstitution after AHSCT encompass early reconstitution, promoted by the homeostatic expansion of cells that survived the conditioning chemotherapy, and late reconstitution, mainly prompted by de-novo thymopoiesis. HSCs, hematopoietic stem cells; TCR, T cell receptor. Created with BioRender.com. Mariottini, A. (2024) BioRender.com/n84b118.
Figure 2
Figure 2
Example of thymic hyperplasia detected by chest CT scan after AHSCT (B) compared to a pre-AHSCT exam (A).
Figure 3
Figure 3
Kinetics of repopulation of CD3+ lymphocyte and CD4+ and CD8+ subsets after AHSCT in individual patients stratified according to thymus appearance on chest CT scan, i.e. hyperplasia (n=3), rebound (n=4) or involution (n=8).
See this image and copyright information in PMC

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