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.
Hematology Department, University Hospital of Larisa, University of Thessaly, PO BOX 1425, Larisa, Greece.
Despina S
DS
Kyriakou
Michael G
MG
Alexandrakis
Kalliopi
K
Zachou
Freda
F
Passam
Nikolaos E
NE
Stathakis
Georgios N
GN
Dalekos
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