Anticardiolipin antibodies in rheumatoid patients treated with etanercept or conventional combination therapy: direct and indirect evidence for a possible association with infections

Ann Rheum Dis. 2002 Apr;61(4):358-61. doi: 10.1136/ard.61.4.358.

Abstract

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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Anticardiolipin / analysis*
  • Antibodies, Antinuclear / analysis
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Child
  • Child, Preschool
  • Chloroquine / therapeutic use
  • Cyclosporine / therapeutic use
  • Drug Combinations
  • Etanercept
  • Humans
  • Immunoglobulin G / analysis
  • Immunoglobulin G / therapeutic use*
  • Immunoglobulin M / analysis
  • Infant
  • Infant, Newborn
  • Methotrexate / therapeutic use
  • Middle Aged
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / immunology
  • Staphylococcus aureus

Substances

  • Antibodies, Anticardiolipin
  • Antibodies, Antinuclear
  • Antirheumatic Agents
  • Drug Combinations
  • Immunoglobulin G
  • Immunoglobulin M
  • Receptors, Tumor Necrosis Factor
  • Cyclosporine
  • Chloroquine
  • Etanercept
  • Methotrexate