Isotype and cytotoxicity spectra of anti-lymphocyte antibodies in patients with systemic lupus erythematosus.
IgG anti-lymphocyte antibodies (ALA) reactive with resting lymphocytes were demonstrated in sera of patients with systemic lupus erythematosus (SLE) by immunofluorescence and flow cytometry and were shown (i) to bind T cells by non-Fc receptor-related mechanisms, (ii) to potentiate antibody-dependent cellular cytotoxicity (ADCC) of lymphocytes in vitro which correlated with binding to T cells, and (iii) to occur at a similar frequency in 29 SLE sera (56%) as IgM ALA (59%). IgG ALA levels in sera negatively correlated with absolute numbers of circulating lymphocytes in patients (r = -0.48, P less than 0.05), as did IgM ALA levels (r = -0.54, P less than 0.05); however, a stronger correlation resulted when levels of both ALA isotypes were considered together (r = -0.61, P less than 0.01). Different groups of SLE patients were distinguished with respect to relative serum content of IgM and IgG ALA and corresponding serum capacity to predominantly mediate ADCC, complement-dependent cytotoxicity (CDC), or both. No correlation existed between serum ADCC and CDC activities in vitro (r = 0.22). However, SLE patient lymphocyte counts negatively correlated with ADCC (r = -0.59, P less than 0.01) and to a lesser but still significant extent with CDC (r = -0.47, P less than 0.05). The latter results suggested that ADCC, induced by serum IgG ALA, was a mechanism of cytoloysis which occurred independently of CDC and which, like CDC, was significantly associated with lymphopenia in vivo.
Edwards
B S
BS
Department of Cell Biology, Lovelace Medical Foundation, Albuquerque, New Mexico 87108.
Searles
R P
RP
Brozek
C M
CM
Richards
R
R
Savage
S M
SM
Nolla
H
H
Hoffman
C L
CL
D001323:Autoantibodies / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005455:Fluorescent Antibody Technique; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007518:Isoantibodies / Q000145:classification; D007958:Leukocyte Count; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007518:Isoantibodies