Complement sensitivity of paroxysmal nocturnal hemoglobinuria bone marrow cells.

Area of Science:

• Hematology
• Immunology
• Stem Cell Biology

Background:

• Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired blood disorder characterized by defective erythrocytes, granulocytes, and platelets.
• These defective cells show increased susceptibility to complement-mediated lysis in vitro.

Purpose of the Study:

• To assess the sensitivity of PNH and non-PNH erythroid and myeloid precursors to complement lysis.
• To investigate the underlying defect in PNH at the hematopoietic stem cell level.

Main Methods:

• Utilized 59Fe release as a marker for complement-mediated lysis of erythroid precursors.
• Employed myeloperoxidase release to monitor complement and antibody-mediated lysis of myeloid precursors.
• Assessed colony-forming unit-culture (CFU-c) growth in the bone marrow of PNH patients.

Main Results:

• Erythroid precursors from all tested PNH patients showed heightened sensitivity to complement-mediated lysis.
• Myeloid precursors from a majority of PNH patients exhibited increased sensitivity to complement and antibody.
• Reduced CFU-c growth was observed in the bone marrow of seven PNH patients.

Conclusions:

• The findings support the hypothesis that the fundamental defect in PNH resides within the hematopoietic stem cell.
• This defect leads to the production of complement-sensitive blood cell precursors.