Study Of NKG2D/MICA Pathway In Primary Billiary Cirrhosis

Objective:To compare frequencies of MICA positive monocytes, of NK cells subsets and the receptors NKG2D on NK cells subsets surfaces in the peripheral blood between primary billiary cirrhosis patients and healthy individuals. Analysis of correlation between MICA expression on monocytes and function-associated receptors expression on NK cells.Explore the roles of the signal transduction pathway NKG2D/MICA in the pathogenesis of primary billiary cirrhosis.Methods:Peripheral blood anticoagulating with heparin from primary billiary cirrhosis patients and healthy individuals were labeled with antibodies in different color. The combinational antibodies were anti-CD45/anti-CD14/anti-MICA, antiCD3/anti-CD56/anti-CD16/anti-NKG2D. Frequencies of MICA positive monocytes, of NK cells subsets and the receptors NKG2D on NK cells surfaces were measured by flow cytometry. Correlation of MICA expression on monocytes with NKG2D was calculated with the linear correlation and regression analysis.Results:1. MICA was seldom detected on normal monocytes, about (2.6±1.9)%, but (51.6±16.2)%on primary billiary cirrhosis, P=0.000<0.05. There was significant difference of frequency of CD14/MICA double positive monocytes between healthy individuals and primary billiary cirrhosis patients.2. Percentages of NK cells were decreased in primary billiary cirrhosis patients(6.8±2.9)%than in healthy donors(16.4±3.4)%. P=0.000<0.05. There was significant difference of frequency of NK cells between the two groups.3. In primary billiary cirrhosis, percentage of CD56positive NK cells (4.2±2.8)%is higher than CD16positive NK cells (1.4±0.7)%, P=0.003<0.05, There was significant difference.4. Percentage of NKG2D on CD56 positive NK cells in primary billiary cirrhosis(79.4±10.2)%is higher than healthy individuals(64.8±10.7)%., P=0.000<0.05, There was significant difference between two groups. But percentage of NKG2D on CD16positive NK cells is (70.1±12.9)%in primary billiary cirrhosis,(61.1±5.9)%in healthy individuals., P=0.078>0.05, There was no significant difference between two groups.5. There was no correlation of MICA expression on monocytes with NKG2D expression on NK cells.Conclusions:1.Frequencies of MICA-positive monocytes were very high in primary billiary cirrhosis patients and very low in healthy individuals. It illustrates that monocytes in PBC is in a "stressed" state. MICA participated in immune response.2. In PBC, the frequence of NK cells in peripheral blood was decreased. It illustrates that on late stage of PBC, maybe NK cells is degenerated.3. In PBC, CD56positive NK is main subsets in NK cells. This implies NK cells plays a immunoregulation role in PBC.4. Activating receptor NKG2D increased in PBC. This implies that maybe activating signal is primary in PBC.5. MICA expressed monocytes in primary billiary cirrhosis patients were recognized by NK cells via the activating immunoreceptor NKG2D. This implies that NKG2D-MICA participates in the pathogenesis of primary billiary cirrhosis.In summary, NKG2D/MICA mediated NK cells activating pathways, participates in the pathogenesis of primary billiary cirrhosis.