Is There a Risk in Allogeneic PBPC Donation for Autoimmune Diseases Due to Short-Term Treatment with rhG-CSF? Preliminary Results of a Prospective Study in 100 Unrelated Stem Cell Donors.
Authors: Kroschinsky Frank , Conrad Karsten , Poppe-Thiede Kirsten , Ordemann Rainer , Schlaupitz Andrea , Rall Gabi , Rutt Claudia , Ehninger Gerhard 
Published: October 2019

Short-term administration of rhG-CSF is a safe and effective procedure for mobilization of allogeneic PBPC in healthy related and unrelated donors. Mild to moderate bone pain is the main side effect occurring in about 80 % of donors, whereas major complications are extremely rare. Recently we observed a patient, who developed life-threatening autoimmune hyperthyreoidism two weeks after rhG-CSF stimulated unrelated PBPC donation (Kroschinsky et al., Haematologica 2004). Anecdotal reports in the literature describe thyroid dysfunction in cancer patients who received rhG-CSF or rhGM-CSF to enhance neutrophil recovery after chemotherapy. In patients with autoimmune disorders who had been treated with rhG-CSG for secondary neutropenia a flare up of disease specific symptoms was observed. Although the current evidence is poor, there might be a potential role of rhG-CSF in thyroid dysfunction and autoimmunity due to its pleotropic effects on different types of cellular and humoral immune effectors.

Therefore we prospectively investigated 104 (27 female, 77 male, median age 36 yrs) unrelated PBPC donors for organ and tissue specific autoantibodies. Mobilization treatment consisted of 7.5 μg/kg body weight lenograstim (Granocyte™, Chugai Pharma Inc., Tokyo, Japan) for five days. Leukaphereses were performed on day 5 and 6. Blood samples were taken at pre-donation health-check (before rhG-CSF stimulation, sample 1), at day of apheresis (sample 2) and four weeks after donation (sample 3). The panel of 21 autoantibodies which was tested sequentially is listed in the table. The frequency of positive findings varied considerably between the different antibody specificities. Whereas none of the donors showed reactivity for antibodies to LKM-1, insulin or proteinase-3, antibodies to endothelial antigens were detected before, at and after donation in 16.5, 13.4 and 17.9 % of donors, respectively. No significant differences were found comparing the number of positive results of the sequential antibody testing. However, there was a significant increase in antibody concentrations measured by immunoassays from sample 1 to sample 3 for anti-TSHR (p=0.02), anti-PR3 (p<0.001) and anti-INS (p=0.001). In contrast concentration of cardiolipin antibodies decrease significantly (IgM p=0.014, IgG p=0.01).

These preliminary results give no evidence for a risk of allogeneic PBPC donors to develop autoimmunity due to rhG-CSF treatment. However there might be a modulatory impact in some antibody specificities which are on further investigation.

Autoantibodies and assays

Immunofluorescence Enzyme- or Radioimmunoassay Smooth muscle ab (SMA) Cardiolipin ab (aCL) Parietal cell ab (PCA) Phosphatidylserin ab (APSA) Antinuclear ab (ANA) Ab to insulin (INS) Antineutrophil cytoplasmic ab(pANCA, cANCA) Ab to Ro60-Sjogren’s syndrome antigen (Ro/SSA) Islet cells ab (ICA) Thyroid ab (anti-TG, anti-TPO, anti-TSHR) Ab targeting endothelial cells (AECA, KE) Ab to myeloperoxidase (MPO) Liver/kidney microsomal ab (LKM-1) Ab to proteinase-3 (PR-3) Ab to soluble liver antigen (SLA/ LP) Ab to insulin (INS) Smooth muscle ab (SMA) Cardiolipin ab (aCL)