Infectious Agents and Bone Marrow Failure: A Causal or a Casual Connection?

Acquired bone marrow failure (BMF) syndromes are considered immune-mediated disorders because hematological recovery after immunosuppressive therapies is the strongest indirect evidence of the involvement of immune cells in marrow failure development. Among pathophysiology hypotheses, immune derangement after chronic antigen exposure or cross-reactivity between viral particles and cellular components are the most accepted; however, epitopes against whom these lymphocytes are directed to remain unknown. In this study, we showed that BMF-associated immunodominant clones, namely the most represented T cells carrying an antigen-specific T-cell receptor (TCR) sequence in a random pool, were frequently associated with those described in various infectious diseases, such as cytomegalovirus (CMV) and Mycobacterium tuberculosis infection. We hypothesize that these pathogens might elicit an autoimmune response triggered by cross-reactivity between pathogen-related components and proteins or might be expanded as an unspecific response to a global immune dysregulation during BMF. However, those frequent intracellular pathogens might not only be passengers in marrow failure development, while playing a central role in starting the autoimmune response against hematopoietic stem cells.

Automated summary

Acquired bone marrow failure (BMF) syndromes are considered immune-mediated disorders, with immune cells possibly playing a role in the development of BMF through chronic antigen exposure or cross-reactivity between viral particles and cellular components. The involvement of immunodominant T-cell clones associated with infectious diseases suggests a potential autoimmune response triggered by pathogens or a global immune dysregulation during BMF. These intracellular pathogens may not only be passengers in the development of marrow failure, but also play a central role in initiating an autoimmune response against hematopoietic stem cells.