AUTOANTIBODY expression in paediatric patients following haematopoietic stem cell transplantation does not reliably predict chronic graft versus host disease, but may reflect broader immune reconstitution patterns, according to findings presented at the 52nd Annual Meeting of the EBMT.
Autoantibody Expression and Immune Reconstitution
Chronic graft versus host disease shares similarities with autoimmune conditions, yet the role of autoantibodies in paediatric transplantation remains unclear. In this single centre study, researchers analysed 440 samples from 74 patients with acute lymphoblastic leukaemia over a median follow up of eight years.
Autoantibodies were detected in 65% of patients, with anti-nuclear antibodies present in 75% of cases. No significant differences were observed in demographic or transplant characteristics between patients with and without autoantibody expression. Overall survival at five years was high at 96%.
Notably, patients with autoantibodies demonstrated significantly improved immune reconstitution, with higher levels of T cells, B cells, and serum immunoglobulins compared with those without autoantibodies.
Immune Dysregulation and Chronic Graft Versus Host Disease
Among patients with both autoantibodies and chronic graft versus host disease, immune alterations were evident. Autoantibody positivity was associated with expansion of CD56 positive natural killer cells (p=0.023) and increased CD21low B cells (p=0.044), indicating B cell perturbation.
Further analysis showed that active chronic graft versus host disease was linked to dysregulated B cell homeostasis, including reduced CD27+ memory B cells (p=0.028) and increased CD21low B cells (p=0.013). However, an unexpected finding emerged when examining patients with elevated CD21low B cells above 7%. A higher prevalence of these cells was observed in autoantibody negative patients with active disease compared with autoantibody positive patients (82% versus 47%; p=0.0053).
Clinical Implications for Biomarker Development
Long term immune recovery was observed in most survivors, with 89% showing normalisation of the B cell compartment. This included increased class switched CD27+IgD– B cells (p<0.0001) and higher immunoglobulin G4 levels (p<0.0001).
Importantly, overall mortality was associated with elevated CD21low B cells (p=0.039) and CD56+ natural killer cells (p=0.019). Multivariate analysis demonstrated that improved survival correlated with lower natural killer cell levels (p=0.041) and higher memory B cell levels (p=0.014).
These findings suggest that while autoantibodies are not reliable biomarkers for diagnosing or predicting chronic graft versus host disease in paediatric patients, specific B cell subpopulations may provide a more accurate reflection of immune dysregulation and disease activity following transplantation.
Reference
Lawitschka A et al. Decoding long-term immune signature through autoantibody expression as persistent immune signals in post-transplant paediatric ALL. Abstract B002. EBMT 52nd Annual Meeting; 22-25 March 2026.
