Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Increased Interferon-Alpha Activity Is Associated with Humoral Autoimmunity and Poor Antigen-Specific Immunity in Systemic Lupus Erythematosus
Cole1, Lauren R., Crowe2, Sherry R., Air1, Gillian M., Thompson2, Linda F., Niewold3, Timothy B., James2, Judith A.
Interferon-a (IFNa) has been identified as a key mediator in systemic lupus erythematosus (SLE) pathogenesis. IFNa is a type I IFN that has the ability to disrupt self tolerance by activating antigen-presenting cells containing self-antigen. Elevated IFNa activity is detected in many SLE patient samples, and these elevations have been shown to correlate with disease activity as well as multiple organ involvement. Our goal is to further understand the pathogenic role of IFNa in SLE humoral autoimmunity, as well as to investigate the effect of an antigen-specific challenge in SLE and whether increased IFNa activity in SLE impairs antigen specific responses.
This study enrolled 72 SLE patients who met ACR criteria and matched controls. Detailed clinical and therapeutic information, as well as disease activity measures were obtained at baseline and 2, 6, and 12 weeks after influenza vaccination. Influenza humoral immune responses (native/denatured ELISA responses, relative affinities and hemagglutination inhibition) were measured. Serial samples were tested for interferon activity through a reporter cell assay which measures serum's ability to upregulate three interferon inducible genes, MX1, PKR, and IFIT1. Lupus-associated autoantibodies (aAbs) (Ro, La, Sm, nRNP, ribosomal P, dsDNA, ANAs and phospholipid antibodies) were measured by ELISA and immunofluorescence.
IFNa activity decreased in SLE patients 2 weeks after influenza vaccination compared to baseline levels (baseline mean = 6.4, 2 weeks post-vaccination mean = 3.9, p=0.0195, paired t-test). However, in the subset of patients whose disease activity scores increased after vaccination, this decrease in IFNa activity was not seen. A correlation was seen between elevated baseline IFNa activity and poor humoral immune response to the influenza vaccine (p=0.0126, r2=0.22). Additionally, a significant association was seen between increased IFNa and total number of lupus-associated autoantibodies (IFNa < 1.0 [n=45], mean aAbs = 2.1, IFNa > 1.0 [n=27], mean aAbs = 3.4, p=0.0003, unpaired t-test). Consistent with previous reports, we also saw a significant association between increased IFNa and disease activity (IFNa < 1.0 [n=45], mean SLEDAI = 7.6, IFNa > 1.0 [n=27], mean SLEDAI = 10.2, p=0.0078, unpaired t-test).
A unique finding in this study was that IFNa decreases in SLE patients post-influenza vaccination. Increased baseline IFNa activity correlated with a poor humoral response to the influenza vaccine. Increased IFNa activity was also associated with an increased number of lupus-associated autoantibodies, as well as with increased disease activity.
To cite this abstract, please use the following information:
Cole, Lauren R., Crowe, Sherry R., Air, Gillian M., Thompson, Linda F., Niewold, Timothy B., James, Judith A.; Increased Interferon-Alpha Activity Is Associated with Humoral Autoimmunity and Poor Antigen-Specific Immunity in Systemic Lupus Erythematosus [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1338