National Institutes of Health –Defined Chronic Graft-vs.-Host Disease in Pediatric Hematopoietic Stem Cell Transplantation Patients Correlates With Parameters of Long-Term Immune Reconstitution

Recent data revealed the importance of immune reconstitution (IR) for the evaluation of possible biomarkers in NIH-defined cGVHD and its clinical aspects. In this large pediatric study (n=146) we have analyzed whether cellular and humoral parameters of IR in the long-term follow-up (FU) with a special emphasis on B-cell reconstitution correlate with NIH-defined cGVHD criteria. HYPOTHESIS: We were especially interested, whether meaningful cGVHD biomarkers could be defined in a large pediatric cohort. We here demonstrate for the first time in a highly homogenous pediatric patient cohort that both cGVHD (n=38) and its activity were associated with the perturbation of the B-cell compartment including low frequencies of CD19+CD27+ memory B-cells and increased frequencies of circulating CD19+CD21low B-cells, a well-known hyperactivated B-cell subset frequently found elevated in chronic infection and autoimmunity. Notably, resolution of cGVHD correlated with expansion of CD19+CD27+ memory B-cells and normalization of CD19+CD21low B-cell frequencies. Moreover, we found that the severity of cGVHD had an impact on parameters of IR and that severe cGVHD was associated with increased CD19+CD21lowB-cell frequencies. When comparing the clinical characteristics of the active and non active cGVHD patients (in detail at time of analyses) we found a correlation between activity and a higher overall severity of cGVHD, which means that in the active cGVHD patient group were more patients with ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research