X-linked agammaglobulinemia (XLA) patients exhibit very low serum immunoglobulin levels, undetectable mature B lymphocytes, and - in most cases- episodes of neutropenia, sometimes reversed by the administration of IV immunoglobulines (IVIG). The aims of the present study were to evaluate the in vitro granulopoiesis in XLA patients, and to study the effects of in vitro immunoglobulins (IG) and in vivo IVIG on their granulopoiesis.

Methods: Peripheral blood (PB) samples were obtained from 15 XLA patients before and after IVIG administration,and from 20 healthy volunteers. The circulating granulocyte-macrophage colony forming cells (GM-CFC) were cultured in GM-CFC colony assay, with or without the addition of IG.

Results: Cultures from PB of XLA patients produced significantly lower numbers of granulocyte-macrophage (GM) colonies than cultures of PB from the normal controls (4±2 Vs 30±10 per 5.10^5 cells). Immediately following IVIG administration, significant rise in the numbers of GM colonies in XLA-derived cultures was detected (20±10 per 5.10^5 cells). The addition of IG directly to the cultures was associated with a rise in the numbers of GM colonies in XLA patients (15±5 Vs 4±2) and with reduction in their numbers in the normal controls (8±3 Vs 30±10).

Conclusions: These results seem to indicate an impairment of granulopoiesis in XLA patients, manifested by significantly low numbers of circulating GM-CFC. The association of this in vitro defect to the neutropenic episodes sometimes occurring in XLA patients is not clear. In view of the newly described genetic defect in XLA, namely the Bruton Tyrosine Kinase (btk) gene located at Xq22, the described granulopoietic impairment may be associated with the deficient btk gene expressed also in the granulopoietic cells of these patients. Immunoglobulins seem to reverse the granulopoietic impairment in these patients, but any proposed mechanism for this would be as of yet highly speculative.