Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Interferon-Alpha Activity Levels Increase Immediately Preceding Clinical Classification of Systemic Lupus.
Robertson1, Julie M., Heinlen2, Latisha, Anderson1, Jourdan, Niewold3, Timothy B., Keith4, Michael P., Harley5, John B., James6, Judith A.
Oklahoma Medical Research Foundation, Oklahoma City, OK
OUHSC, Oklahoma City, OK
University of Chicago, Chicago, IL
National Naval Medical Center, Bethesda, MD
Cincinnati Children's Hospital Medical Center and the US Department of Veterans Affairs Medical Center, Cincinnati, OH
Oklahoma Medical Research Foundation and Oklahoma University Health Sciences Center, Oklahoma City, OK
Systemic lupus erythematosus (SLE) is a clinically variable disease with a complex etiology. Many lupus patients have increased interferon-inducible gene expression and elevated levels of interferon-a (IFNa) which correlate with increased disease activity. IFNa is released by plasmacytoid dendritic cells after stimulation through TLR binding by autoantigen/autoantibody complexes. However, the exact role of interferon in disease pathogenesis is still not understood. This study seeks to evaluate the temporal relationship between IFNa production and the onset of SLE characteristics.
Patient sera from 20 SLE cases with samples spanning from no ACR criteria to SLE classification were obtained from the Department of Defense Serum Repository (DODSR). Serial samples were tested for antibody isotype specificity against common lupus autoantigens (Ro, La, nRNP, Sm, Ribosomal P, dsDNA, and ANA) by ELISA and immunofluorescence. IFNa levels were examined utilizing a cell reporter assay measuring upregulation of interferon inducible genes (MX1, PKR, and IFIT1) by serum. Two sets of matched controls were also tested and results were reported as elevation of IFN levels above controls.
Autoantibodies are common before diagnosis in SLE patient samples. As a patient moved toward SLE diagnosis the number of autoantibodies increased to include specificity toward multiple lupus autoantigens. Isotype class switching from IgM to IgG1 was observed in the anti-Ro specificity. In examining dominant antibody isotypes for each lupus antigen we observed the IgG1 isotype as dominant in nRNP, while Ro, Sm, and Ribo P had an IgG2 isotype dominance before and at lupus classification. Interestingly, anti-La, anti-Sm, and anti-nRNP antibodies specificities showed detectable amounts of IgA and IgE antibody isotypes. Examination of IFNa levels indicated a statistically significant trend of increasing IFN levels leading up to SLE diagnosis (p=0.0279). There was a significant difference in IFN levels between samples prior to first criteria and at SLE diagnosis (p<0.05). Four individuals are shown to have autoantibody present in sera samples before the detection of serologic interferon activity.
Our results show IgG2 is the dominant autoantibody specificity, class switching between IgM and IgG1 for anti-Ro antibodies occurs leading up to diagnosis, and IFNa levels increase as the number of autoantigen specific antibodies increase leading up to SLE classification. Thus, the increase in IFN levels is more closely linked to disease onset as opposed to autoantibody production.
To cite this abstract, please use the following information:
Robertson, Julie M., Heinlen, Latisha, Anderson, Jourdan, Niewold, Timothy B., Keith, Michael P., Harley, John B., et al; Interferon-Alpha Activity Levels Increase Immediately Preceding Clinical Classification of Systemic Lupus. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2601