The Association of Fine Specificities of Anti-Citrullinated Protein Antibodies (ACPA) with disease Severity in African-Americans with RA

Maria I. Danila¹, Richard Reynolds², Gordon Wu³, Hemant Tiwari³, William H. Robinson⁴, Jeremy Sokolove⁵, CLEAR Investigators² and S. Louis Bridges Jr.^2,6, ¹Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, ²University of Alabama at Birmingham, Birmingham, AL, ³Biostatistics, University of Alabama at Birmingham, Birmingham, AL, ⁴VA Palo Alto Health Care System and Stanford University, Palo Alto, CA, ⁵VA Palo Alto Healthcare System and Stanford University, Palo Alto, CA, ⁶Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, AL

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: anti-citrullinated protein/peptide antibodies (ACPA), joint damage and rheumatoid arthritis (RA)

Session Information

Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose: RA is characterized by the presence of autoantibodies to citrullinated proteins (ACPA) and joint damage. The role of fine specificities of ACPA in radiographic severity has not been defined. The purpose of the current study was to evaluate whether fine specificities of ACPA are associated with radiographic severity of RA in African Americans.

Methods: Using a custom Bio-Plex™ bead-based autoantibody assay platform, we measured anti-CCP antibody and 19 autoantibodies targeting citrullinated proteins and peptides (vimentin, fibrinogen, histone 2A , histone 2B, and apolipoprotein E, clusterin, biglycan, enolase, fillagrin). We analyzed sera from 692 African-American patients with RA. A total antibody score was defined for each patient as the standardized sum of the log transformed autoantibodies . The total antibody score was used as predictor variable for radiographic severity. Radiographic severity defined as total Sharp/van der Heijde scores of hands/feet was the dependent variable. Zero-inflated negative binomial regression models were used to test the association of the autoantibody score with radiographic severity defined as total Sharp/van der Heijde scores of hands/feet given the covariates gender, BMI, smoking status and disease duration.

Results: High correlation coefficients among the autoantibodies were observed. Using zero-inflated negative binomial regression, the total sum of standardized antibodies had a statistical significant (p-value =0.002) effect among patients with a total RA radiographic severity (total score >0). For each unit increase in the total sum of standardized autoantibodies, the total radiographic score increases by 0.3 units. In addition, disease duration was found to be statistically significant (p-value <0.0001).

Conclusion: Autoantibodies against citrullinated autoantigens are associated with joint damage in this cross sectional study of African Americans with RA. Future work will focus on longitudinal aspects of antibodies to specific peptides/proteins and their role in progression of radiographic damage.

Disclosure:

M. I. Danila,
None;

R. Reynolds,
None;

G. Wu,
None;

H. Tiwari,
None;

W. H. Robinson,
None;

J. Sokolove,
None;

C. Investigators,
None;

S. L. Bridges Jr.,
None.

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