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.


Early Systemic Lupus Erythematosus Specific Antigens Predict Disease Characteristics.

Hale1,  Jessica J., Kelly1,  Jennifer A., Lin1,  Chee Paul, Glenn1,  Stuart B., Anderson1,  Jourdan, Gaffney2,  Patrick M., Moser2,  Kathy L.

Oklahoma Medical Research Foundation, Oklahoma City, OK
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK
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

Background/Purpose:

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, most prevalent in women of child-bearing age. It is characterized by autoantibody production leading to inflammation and ultimately, tissue damage. Some autoantibodies precede clinical disease by several years, are unique to SLE and have antigenic peptide sequences that closely mimic that of a suspected environmental trigger Epstein-Barr Virus (EBV). The objective of this study was to assess the relationship between early humoral autoimmune responses, select viral responses and the varied manifestations of SLE in both European and African American (EA and AA) patients to better characterize SLE etiology.

Methods:

Data were collected for 519 AA and 1210 EA female SLE patients. Individual and familial correlation analyses were performed to determine the extent early epitope and viral production are associated with lupus clinical and lab criteria. Data included quantitaive measures of antibodies against: SmB' amino acids (aa) 191–198 (GMR), SmD1 aa 95–119 (GRx4) and 60kDRo aa 169–182 (Ro169), EBV viral capsid antigen (VCA), EBV nuclear antigen 1 (EBNA-1) EBNA-1 aa 398–404 (GRR), ENBA-1 aa 58–72 (EBNA58) and EBNA-1 aa 1–90 and 409–497 (EBNA1M). We also evaluated the 11 ACR criteria, CH50, anticardiolipin (APL) IgG and IgM as well as the following autoantibodies: nuclear (ANA), double stranded DNA (dsDNA), Ro, La, P, nRNP. Transformations were applied where necessary to achieve normality. We assessed self and familial correlations using FCOR (S.A.G.E. software suite) and used a threshold for significance of 5 = 10-4. Significant correlations were confirmed using linear regression in SAS.

Results:

In the EA females, increased levels of EBV-VCA corresponded to the presence of six of the 11 ACR criteria, including hematologic, immune, skin and renal systems (p<2 = 10-4). We also found both EBV-VCA and GRR to be significantly correlated with levels of APL-IgG (p=1.7 = 10-4 and 4 = 10-6). Anti-GMR was positively correlated with anti-Sm, -RNP, -dsDNA, -ssDNA, -ANA, as well as IgG antibodies in EAs (p<1 = 10-4) and with anti–Sm, -RNP and –dsDNA in AAs (p<1 = 10-4). Anti-GMR was negatively correlated with CH50 titers in both EAs and AAs (p=1.5 = 10-4 and 4.9 = 10-4). Also in both EAs and AA, anti-GRx4 was strongly, negatively correlated with renal involvement (p=4.6 = 10-3 and 3.2 = 10-3). Sibling correlations were significant for anti-GMR in EAs and anti-EBV-VCA in AAs (p=1.2 = 10-5 and 7.5 = 10-4).

Conclusion:

High levels of EBV-VCA antibodies predict multi-system involvement in EAs and perhaps AAs as well. Similarly, high levels of anti-GMR in both EAs and AAs are indicative of an array of autoantibodies and of disease severity (as indicated by low CH50 levels). Conversely, high anti-GRx4 levels indicate that a patient is less likely to have renal involvement, regardless of ethnicity. Significant sibling correlations support a genetic component to the interplay of EBV infection and autoimmune response. Finally, the results of this study highlight the potential to predict disease outcome based on early indicators of SLE and a suspected viral trigger.

To cite this abstract, please use the following information:
Hale, Jessica J., Kelly, Jennifer A., Lin, Chee Paul, Glenn, Stuart B., Anderson, Jourdan, Gaffney, Patrick M., et al; Early Systemic Lupus Erythematosus Specific Antigens Predict Disease Characteristics. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1370
DOI:

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