Anticardiolipin antibodies in rheumatoid patients treated with etanercept or conventional combination therapy: direct and indirect evidence for a possible association with infections.
OBJECTIVE
To assess the occurrence of anticardiolipin antibodies (ACA) (as well as of anti-DNA antibodies) in patients with rheumatoid arthritis treated with etanercept or combination therapy.


METHODS
Eight patients treated with etanercept 25 mg twice weekly were studied for a period of 85 weeks. A control group of 39 patients with rheumatoid arthritis undergoing combination treatment (methotrexate (MTX) + cyclosporin A or MTX + chloroquine) were studied for the same period of time. The occurrence of anticardiolipin antibodies (ACA-IgG) and anti-DNA was examined, together with the possible occurrence of infections due to bacteria capable of inducing B cell activation.


RESULTS
In 5/8 patients receiving etanercept an increase of ACA-IgG was seen, while anti-DNA became positive in 3/8 patients. A nasal or bronchial infection due to Staphylococcus aureus (Staph aureus) or a urinary tract infection due to E coli, occurred in all five cases. Antibiotic treatment produced a return to normal of ACA-IgG, and also of anti-DNA, in all cases except one. The infectious agent was eradicated in all subjects but one. In the control group Staph aureus was found in the nasal swab in 10/39 subjects; ACA-IgM (followed by ACA-IgG) appeared at the same time as infection occurred in 6/10, while no infection related to the increased ACA-IgM was recorded in the other four.


CONCLUSIONS
Bacterial DNA, especially that enriched in CpG motifs, is a powerful immunostimulant that may, in some cases, lead to ACA or anti-DNA positivity, once tumour necrosis factor alpha is blocked. Eradication of the infections leads to a rapid decrease of ACA-IgG and of anti-DNA levels.
Ferraccioli
G
G
Chair and Division of Rheumatology, DPMSC, Udine University Medical Centre, University of Udine, 33100 Udine, Italy. gf.ferraccioli@med.uniud.it
Mecchia
F
F
Di Poi
E
E
Fabris
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D017153:Antibodies, Anticardiolipin / Q000032:analysis*; D000974:Antibodies, Antinuclear / Q000032:analysis; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D004338:Drug Combinations; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000627:therapeutic use*; D007075:Immunoglobulin M / Q000032:analysis; D007223:Infant; D007231:Infant, Newborn; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000276:immunology; D013211:Staphylococcus aureus
D017153:Antibodies, Anticardiolipin; D000974:Antibodies, Antinuclear; D018501:Antirheumatic Agents; D004338:Drug Combinations; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D018124:Receptors, Tumor Necrosis Factor; D016572:Cyclosporine; D002738:Chloroquine; D000068800:Etanercept; D008727:Methotrexate