Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases.
OBJECTIVE
To determine whether serum levels of B lymphocyte stimulator (BLyS) are elevated in patients with systemic immune-based rheumatic diseases and correlate with serum Ig levels and/or autoantibody titers.


METHODS
Sera from 185 patients with various systemic immune-based rheumatic diseases (95 with systemic lupus erythematosus [SLE], 67 with rheumatoid arthritis [RA], 23 with other diagnoses) were assayed for BLyS and Ig. In 7 patients who required arthrocentesis of a swollen knee, coincident serum and synovial fluid samples were assayed for BLyS. Medical charts were retrospectively reviewed for elevated autoantibody titers and proteinuria within a 1-month period before or after collection of sera for BLyS and Ig determination. Sera concurrently collected from 48 normal healthy subjects served as controls.


RESULTS
Serum BLyS levels were elevated in 38 of 185 patients (21%) and correlated significantly with serum IgG levels. Serum BLyS levels did not correlate with the patients' age, sex, race, or medications, but correlated positively with anti-double-stranded DNA antibody titers among SLE patients and with rheumatoid factor titers among seropositive RA patients. In contrast, serum BLyS levels correlated inversely with nephrotic-range proteinuria among SLE patients. In every case tested, BLyS levels in clinically inflamed synovial fluids were greater than those in simultaneously obtained sera.


CONCLUSIONS
BLyS may be an important factor in driving polyclonal hypergammaglobulinemia and elevated autoantibody titers in patients with systemic immune-based rheumatic diseases. Local production of BLyS in the joints may contribute to joint pathology. Patients with elevated serum BLyS levels may be ideal candidates for therapeutic targeting of BLyS.
Cheema
G S
GS
Los Angeles County + University of Southern California Medical Center, University of Southern California, 90033, USA.
Roschke
V
V
Hilbert
D M
DM
Stohl
W
W
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D053264:B-Cell Activating Factor; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000097:blood*; D008875:Middle Aged; D012189:Retrospective Studies; D012216:Rheumatic Diseases / Q000097:blood* / Q000276:immunology; D012217:Rheumatoid Factor / Q000097:blood; D013582:Synovial Fluid / Q000737:chemistry / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000974:Antibodies, Antinuclear; D053264:B-Cell Activating Factor; D007074:Immunoglobulin G; D008565:Membrane Proteins; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha; D012217:Rheumatoid Factor