Neutrophil and platelet antibodies in autoimmune lymphoproliferative syndrome.
OBJECTIVE
Autoimmune lymphoproliferative syndrome (ALPS), is an inherited disorder characterized by defective lymphocyte apoptosis, lymphadenopathy, splenomegaly, accumulation of T-cell receptor (TCR)-alphabeta+ CD4- CD8- T cells (double-negative T cells) and autoimmunity. We investigated the incidence and nature of neutrophil and platelet antibodies in patients with ALPS.


METHODS
Sera from 26 patients with ALPS were tested for neutrophil antibodies by granulocyte immunofluorescence, granulocyte agglutination and monoclonal antibody immobilization assays of granulocyte antigens, and for platelet antibodies using a solid-phase antibody-detection system.


RESULTS
Neutrophil antibodies were detected in 46% of patients with ALPS. Antibody specificity could be defined in eight of the 12 patients with neutrophil antibodies. Among these eight patients, four had antibodies directed against more than one antigen. Overall, 14 antibodies directed to specific antigens were identified: three were directed to the HNA-1a antigen of FcgammaRIIIb; two to the HNA-1b antigen of Fcgamma-RIIIb; two to epitopes common to all FcgammaRIIIb molecules; four to the HNA-2a antigen of the NB1 glycoprotein; and three to neutrophil beta2 integrins. Platelet antibodies were detected in 35% of patients with ALPS. No antibody specificities were identified among the platelet antibodies. There was no association between the detection of neutrophil antibodies and a history of clinical neutropenia, or between the detection of platelet antibodies and a history of clinical thromobocytopenia.


CONCLUSIONS
Neutrophil and platelet antibodies are important markers of ALPS, but do not always cause clinical cytopenias. The specificities of neutrophil antibody were similar to those found in children with autoimmune neutropenia but without ALPS.
Kwon
S-W
SW
Department of Transfusion Medicine, Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1184, USA.
Procter
J
J
Dale
J K
JK
Straus
S E
SE
Stroncek
D F
DF
D000293:Adolescent; D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000097:blood; D000974:Antibodies, Antinuclear / Q000097:blood; D000918:Antibody Specificity; D015703:Antigens, CD; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000601:surgery; D001792:Blood Platelets / Q000276:immunology*; D018821:CD18 Antigens / Q000276:immunology; D002648:Child; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D006971:Hypersplenism / Q000209:etiology / Q000601:surgery; D007519:Isoantigens / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology* / Q000601:surgery; D008297:Male; D009504:Neutrophils / Q000276:immunology*; D011506:Proteins / Q000235:genetics; D017452:Receptors, IgG; D018124:Receptors, Tumor Necrosis Factor; D013156:Splenectomy; D019014:fas Receptor
D017153:Antibodies, Anticardiolipin; D000974:Antibodies, Antinuclear; D015703:Antigens, CD; D001323:Autoantibodies; D001324:Autoantigens; D018821:CD18 Antigens; C491901:FAS protein, human; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D007519:Isoantigens; D011506:Proteins; D017452:Receptors, IgG; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor