Historical notesPatients previously immunized with multiple transfusions, pregnancy, or organ transplantation were initially shown to develop antibodies (Ab) with cytotoxic activity against allogenic lymphocytes. Later, allogenic-independent lymphocytotoxins were described in patients with infectious diseases. These infection-related lymphocytotoxins possess two characteristics: first, they are immunoglobulin (Ig) M-like in nature, and second, they present optimal activity at 15 °C. Accordingly, they are referred to as cold lymphocytotoxins (CLTs). Finally, using a mixed lymphocyte cytotoxic (MLC) assay, developed for histocompatibility testing, the presence of autologous lymphocytotoxic Ab (LCA) was tested and demonstrated, even at 37 °C, in patients with systemic lupus erythematosus (SLE). These LCA appeared to reflect the clinical course of SLE and to target T rather than B lymphocytes. Furthermore, they were relatively specific for mitogen-activated T lymphocytes and shown to recognize predominantly different isoforms of CD45. All of these Ab are referred to as LCA.
The autoantigens DefinitionSera reactive for LCA react with: 1) peripheral blood mononuclear cells (PBMC) obtained from healthy donors; 2) T and B lymphocytes isolated from PBMC; 3) cells from permanent T-and B-cell lines; and 4) cytokine or pokeweed mitogen activated lymphocytes.LCA are not lymphocyte-specific since the activity can be partially inhibited by absorption with brain tissue, red blood cells, and platelets. The binding is not mediated by Fc receptors.
CD45 is the main targetThe leukocyte common antigen CD45 is an essential tyrosine phosphatase for efficient T-and B-lymphocyte antigen receptor signal transduction. Five CD45 isoforms can be generated by alternative splicing of exons 4(A), 5(B), and 6(C) that encode the corresponding domains at the N-terminal extracellular portion of the protein (Fig. 63.1). These glycoproteins vary both in size, with a molecular weight ranging from 180 to 240 kDa, and in glycosylation, with N-and/or O-linked polysaccharides. Isoforms and carbohydrate composition are related to the T-or B-lymphocyte subsets and to the lymphocyte maturation and differentiation status [1].