Transient Marked Increase of γδ T Cells in WHIM Syndrome After Successful HSCT

WHIM syndrome: Immunopathogenesis, treatment and cure strategies

“…The feasibility of transplantation as a cure strategy in WHIM syndrome has not only been demonstrated by WHIM‐09 who has remained healthy for at least two decades after the presumed genetic event that repopulated her bone marrow but also by four successful bone marrow transplantations in three pediatric and one adult WHIM patient . One of these involved a related donor and three involved a matched unrelated transplant.…”

“…Silencing may be a superior strategy since CXCR4 hemizygous hematopoietic stem cells (HSCs) have a selective advantage for engraftment over WHIM HSCs after syngeneic transplantation in a mouse model of WHIM syndrome as well as in a patient cured of the disease spontaneously by fortuitous chromothriptic deletion of the WHIM allele in an HSC 72,80 The feasibility of transplantation as a cure strategy in WHIM syndrome has not only been demonstrated by WHIM-09 who has remained healthy for at least two decades after the presumed genetic event that repopulated her bone marrow but also by four successful bone marrow transplantations in three pediatric and one adult WHIM patient. [81][82][83][84] One of these involved a related donor and three involved a matched unrelated transplant. While the conditioning regimens have varied, to date problems with graft-versus-host disease (GVHD) have been minimal, leukocyte numbers have normalized within months after transplantation, and HPV disease has not occurred.…”

Adaptive Immunodeficiency in WHIM Syndrome

“…WHIM patients may have hypogammaglobulinemia, markedly reduced circulating B cells [1,3,4,15,17,18,19,35,36,38,43,70,71,72], restricted immunoglobulin heavy chain variable region diversity, impaired class switching [71], and poor or unsustained responses towards vaccines [1,3,4,19,20,38,71]. Hypogammaglobulinemia may involve one or more of the immunoglobulin classes.…”

“…Nevertheless, despite the increase in the cellularity after AMD3100 treatment and B cells demonstrating class switching in vitro, serum Ig levels could not be successfully elevated, and pneumococcal and diphtheria/tetanus vaccinations were not successful in eliciting antibody responses [38]. Hematopoietic stem cell transplantation (HSCT) has been reported to correct leukopenia including B lymphopenia and hypogammaglobulinemia in WHIM patients and has been successfully accomplished in three patients [35,72,75]. Of note, in one patient, although B cell numbers and IgG levels were increased, IgA levels remained low [35].…”

“…To date, only four patients have been clinically cured of WHIM syndrome, of which three received allogeneic hematopoietic stem cell transplantation [35,72,75], whereas the fourth patient, WHIM-09, underwent spontaneous chromothripsis as mentioned previously [15]. Serendipitous removal of the disease allele from cells specifically belonging to the myeloid and not the lymphoid lineage cured patient WHIM-09 [15].…”