Bone marrow findings in patients with autoimmune liver diseases.

BACKGROUND AND AIMS: We have recently reported quantitative and qualitative differences of the bone marrow (BM) hematopoietic progenitor cells in autoimmune hepatitis type-1 (AIH-1) and primary biliary cirrhosis (PBC). In order to better investigate the possible involvement of BM in these diseases, we studied the morphological abnormalities of BM aspirates in the same patients with AIH-1 and PBC. METHODS: BM smears from 13 AIH-1 and 13 PBC patients were investigated. BM from 12 patients with cirrhosis of non-autoimmune etiology and eight healthy individuals served as pathological (PC) and healthy controls (HC). RESULTS: Erythroid, granulocyte and platelet precursors were variably altered. Polychromatic normoblasts and immature megakayocytes were higher in AIH-1 (11.9 +/- 2.9 and 16.2 +/- 16.9, respectively) and PBC (10.2 +/- 3.6 and 17.3 +/- 20.2, respectively) compared to PC (7 +/- 2 and 2.3 +/- 6.0, respectively) and HC (7.9 +/- 1.6 and 0 +/- 0, respectively) (P = 0.0001 and P = 0.006). In AIH-1, immature megakaryocytes were significantly higher in patients receiving immunosuppression (25.71 +/- 17.66 vs 5.00 +/- 5.48; P < 0.02) and were associated negatively with laboratory markers of disease activity. BM plasmacytosis was observed more frequently in AIH-1 compared to PBC and PC. BM monocytosis was found in all patients with AIH-1, PBC and PC whereas approximately half of the patients with autoimmune liver diseases and all PC had BM lymphocytosis. CONCLUSIONS: BM monocytosis and lymphocytosis are commonly found in AIH-1 and PBC patients irrespective of the presence of cirrhosis or the use of immunosuppression. BM plasmacytosis appears to be a distinct finding in some AIH-1 patients, as similar findings were observed in only one PBC and one PC, whereas BM immature megakaryocytes characterize both AIH-1 and PBC. Whether BM is a target organ in AIH-1 and PBC needs further investigation.

Autoimmune hepatitis type 1 and primary biliary cirrhosis have distinct bone marrow cytokine production.

We have recently reported differences in the hematopoiesis between autoimmune hepatitis type 1 (AIH-1) and primary biliary cirrhosis (PBC). In view of the notion that cytokines are regulators of hematopoiesis, we investigated in our tertiary center the cytokine production in the bone marrow (BM) of the same consecutive cohort of patients (13 AIH-1, 13 PBC, 10 healthy and 7 patients with cirrhosis due to chronic hepatitis B). Interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) were determined in the supernatants of long-term BM cultures by ELISAs. IL-4, TNF-alpha and TGF-beta were found significantly increased in the BM of PBC patients compared to AIH-1 and both control groups. AIH-1 patients had significantly higher BM IL-10 compared to PBC patients and higher IL-10, IL-4 and TNF-alpha compared to controls. BM IFN-gamma was significantly higher in PBC and AIH-1 patients compared to controls. In AIH-1 patients, IL-10 was positively correlated with CD34+, CD34+/CD38- and CD34+/CD38+ cell proportions. In conclusion, the BM cytokine microenvironment of PBC and AIH-1 patients differs significantly compared to that of healthy individuals and cirrhotic patients of non-autoimmune etiology. Differences were also found between patients with PBC and AH-1. The implication of BM in the pathogenesis of autoimmune liver diseases is possible and needs further investigation.

Markers of cell activation and apoptosis in bone marrow mononuclear cells of patients with autoimmune hepatitis type 1 and primary biliary cirrhosis.

BACKGROUND/AIMS: We have reported quantitative and qualitative differences in bone marrow (BM) progenitor cells in autoimmune hepatitis type-1 (AIH-1) and primary biliary cirrhosis (PBC). This study investigated the apoptotic features and cytokine suppressors of haematopoiesis in long-term cultures of BM mononuclear cells (BMMCs) from AIH-1 and PBC patients. METHODS: Apoptotic markers and CD14 expression were evaluated in 13 AIH-1 patients, 13 PBC patients, 12 cirrhotic controls and 10 healthy subjects. TNF-alpha, TGF-beta and IFN-gamma were determined using ELISAs. RESULTS: All apoptotic markers and CD14 were increased in AIH-1 and PBC compared to controls (P<0.0001). Fas+ cells were positively correlated (P=0.0001) with apoptotic cells in AIH-1 and PBC. TNF-alpha and IFN-gamma were higher in AIH-1 (P=0.003 and P=0.001) and PBC (P=0.0001) compared to controls. No differences were found between the control groups. CONCLUSIONS: We demonstrate for the first time that the apoptotic process, macrophage activation and the production of cytokine suppressors of haematopoiesis in BMMCs from AIH-1 and PBC patients are higher compared to controls. The Fas-FasL pathway is likely to be involved in the apoptotic process; the increased levels of selected cytokines may contribute to Fas-FasL stimulation. Cirrhosis appears unlikely to be the cause of the above findings.