PS1143 AUTOIMMUNIZATION TO PLATELET ANTIGENS IN CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: Isaeva N. , Maximov O. , Butina E. , Kiseleva A. 
Published: June 2019

Background:

The development of thrombocytopenia in chronic lymphocytic leukemia (CLL) can be enhanced by autoimmune cell destruction. The cause of anti‐platelet autoimmunization in CLL is associated with disturbance of the immune system tolerance to its own platelet antigens.

Aims:

To determine the importance of antiplatelet autoimmunization in thrombocytopenia at the stage of manifestation of CLL and to identify features of immunoreactivity in these patients.

Methods:

Under supervision there were 59 patients with CLL in the debut of the disease. All studies in patients performed before treatment. The content of anti‐platelet antibodies was determined using a FACS Canto II laser flow cytometer (Becton Dickinson). An excess of the permissible value of autoantibodies considered the binding of more than 3% of the patient's platelets with FITC‐conjugated monoclonal antibodies to human IgG during incubation with autologous serum. The content of T‐lymphocytes, their subpopulations, and natural killer cells was evaluated. The degree of expression of CD3, CD4, CD8 and CD45 molecules within lymphoid populations and subpopulations was taken into account in terms of the average intensity of immunofluorescence. The concentrations of IgG, IgA and IgM was determined in an enzyme immunoassay. The statistical significance of differences was assessed using the Mann‐Whitney test, differences were considered significant at p < 0.05.

Results:

The group of patients with increased autoantibodies to platelets included 15 (25.4 %) people, the group without increase – 44 (74.6 %) people. The number of platelets in peripheral blood was significantly lower in patients with antibodies compared with patients without autoimmunization (121 [90; 167] x 109/l versus 187 [160; 235] x 109/l, p < 0.01). A comparative analysis of cellular and humoral immunity parameters in groups of patients with CLL with different levels of autoantibodies was carried out. The values of the absolute content of T‐lymphocytes, T‐helper cells and cytotoxic T‐lymphocytes (phenotype: CD3+CD19‐, CD3+CD4+, CD3+CD8+), lymphocytes with the function of natural killer cells (phenotype: CD3‐CD8+, CD3‐CD(16+56)+ and CD3+CD(16+56)+), late activated T lymphocytes (CD3+HLA‐DR+) in groups of patients did not differ. Significantly lower levels of CD3 molecules on the membrane of T‐lymphocytes (4,9 [4,2; 5,5] conv. units against 5,7 [5,2; 6,7] conv. units p < 0.01) and CD4 molecules on the t‐helper membrane (5.1 [4.2; 6.4] conv. units versus 7.8 [7.1; 8.4] conv. units, p < 0.01) was registered in patients with CLL with increased antiplatelet antibodies. In the groups of patients there were no differences in the level of immunoglobulins of classes G and a in serum. Significantly higher content of immunoglobulin class M in patients with autoimmunization than in patients without antibodies (1,6 [1,3; 1,7] g/l versus 1,1 [1,0; 1,3] g/l, p < 0,05) was detected.

Summary/Conclusion:

Antiplatelet autoimmunization is observed in a quarter of patients with CLL at the stage of diagnosis of the disease. If IgG is attached to the surface membrane of platelets, cells undergo accelerated damage in the reticular‐endothelial system, which, along with other causes, leads to a decrease in their number in the blood. It was found that in patients with CLL autoimmunization to platelet antigens is associated with increased anergy of T‐lymphoid elements, increased serum IgM levels.