Hemopoietic progenitor cells and bone marrow stromal cells in patients with autoimmune hepatitis type 1 and primary biliary cirrhosis.
OBJECTIVE
Autologous hematopoietic stem cell transplantation has been used in severe cases of autoimmunity. We investigated whether hemopoietic progenitor cells and/or bone marrow (BM) microenvironment are affected in autoimmune hepatitis type-1 (AIH-1) and primary biliary cirrhosis (PBC).


METHODS
We studied 13 AIH-1 patients, 13 PBC patients, 12 cirrhotic controls (CC) and ten healthy controls (HC). Flow cytometry, expansion cultures, long-term BM cultures and clonogenic progenitor cell assays were used. Stromal cell function was assessed in long-term BM cultures recharged with normal CD34+ cells.


RESULTS
AIH-1 had increased CD34+, CD34+/CD38+ and CD34+/CD38- cells compared to all groups (P<0.001). PBC had lower progenitor cells compared to controls (P<0.005). No differences were found between CC and HC. Committed progenitor cells in non-adherent cell fraction were increased in AIH-1 (P<0.05) but decreased in PBC compared to controls (P<0.05). Granulocyte-macrophage colony forming units (CFU) and erythroid-burst CFU were increased in AIH-1 compared to all groups (P<0.001). PBC had these CFUs decreased compared to controls (P<0.005). Stromal cells failed to support normal hemopoiesis in PBC.


CONCLUSIONS
We demonstrated for the first time that AIH-1 had increased hemopoietic progenitor cells and normal stromal function. In PBC, progenitor cells and BM microenvironment were defective. Further studies will determine the significance of these novel findings.
Kyriakou
Despina S
DS
Hematology Department, University Hospital of Larisa, University of Thessaly, PO BOX 1425, Larisa, Greece.
Alexandrakis
Michael G
MG
Zachou
Kalliopi
K
Passam
Freda
F
Stathakis
Nikolaos E
NE
Dalekos
Georgios N
GN
D036541:ADP-ribosyl Cyclase / Q000032:analysis; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D002448:Cell Adhesion; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology*; D019693:Hepatitis, Autoimmune / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D008562:Membrane Glycoproteins; D008875:Middle Aged; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*
D015703:Antigens, CD; D018952:Antigens, CD34; D008562:Membrane Glycoproteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1