Kidney Week

Abstract: FR-PO828

Antibodies to Plasminogen and a Pathogenic Myeloperoxidase (MPO) Epitope Precede MPO- and Proteinase 3-ANCA in Patients with ANCA Vasculitis

Session Information

• Glomerular Diseases: Immunology, Inflammation - I
  November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1202 Glomerular Diseases: Immunology and Inflammation

Authors

• Mendoza, Carmen E., UNC Kidney Center, Chapel Hill, North Carolina, United States

Carmen E. Mendoza,

• Bunch, Donna O., UNC Kidney Center, Chapel Hill, North Carolina, United States

Donna O. Bunch,

• Kennedy, Kristin Brock, UNC Kidney Center, Chapel Hill, North Carolina, United States

Kristin Brock Kennedy,

• Hogan, Susan L., UNC Kidney Center, Chapel Hill, North Carolina, United States

Susan L. Hogan,

• Hu, Yichun, UNC Kidney Center, Chapel Hill, North Carolina, United States

Yichun Hu,

• Little, Dustin J., AstraZeneca, Gaithersburg, Maryland, United States

Dustin J. Little,

• Poulton, Caroline J., UNC Kidney Center, Chapel Hill, North Carolina, United States

Caroline J. Poulton,

• Henderson, Candace Dione, UNC Kidney Center, Chapel Hill, North Carolina, United States

Candace Dione Henderson,

• Jennette, J. Charles, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

J. Charles Jennette,

• Falk, Ronald J., UNC Kidney Center, Chapel Hill, North Carolina, United States

Ronald J. Falk,

• Olson, Stephen W., Walter Reed National Military Medical Center, Bethesda, Maryland, United States

Stephen W. Olson,

Background

The preclinical immunopathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis has not been elucidated. Antibodies to plasminogen (anti-PLG) and a specific epitope of myeloperoxidase (MPO^447-459, anti-KIV) are associated with active disease. The presence of these antibodies has not been examined prior to diagnosis. We hypothesized that anti-PLG and anti-KIV precede detectable MPO-ANCA and proteinase 3 (PR3)-ANCA.

Methods

Up to 4 serum samples collected before clinical diagnosis were available from 64 patients with ANCA vasculitis (50 PR3, 12 MPO, 2 unknown) and 63 healthy controls (HC) matched for age, gender, ethnicity, and timing of sample through the Department of Defense Biorepository. Anti-PLG, anti-KIV, MPO- and PR3-ANCA were measured by ELISA. Analyses accounted for matched pairs using McNemar tests and odds ratios and 95% confidence intervals from stratified exact conditional logistic regression.

Results

Anti-PLG was detected in 17/64 (27%) of cases prior to diagnosis (median = -8.8 years [IQR -13.1, -2.0]). Anti-PLG was positive before ANCA in 76% (13/17) of cases where both were positive.

Anti-KIV was detected in 21/64 (33%) of cases prior to diagnosis (-6.6 years [-15.0, -4.1]), was elevated before ANCA in 71% (15/21) cases, and elevated when MPO-ANCA was negative in 33% (4/12) of MPO-ANCA patients.

ANCA patients were more likely to have elevated anti-PLG and anti-KIV than matched controls (Table). Limiting analysis to PR3-ANCA patients, the odds ratio for anti-PLG remained statistically significant; the odds ratio for anti-KIV was the same albeit not statistically significant.

Conclusion

Anti-KIV and anti-PLG antibodies are present years before diagnosis and prediagnostic ANCA seropositivity. Thus, anti-KIV and anti-PLG may participate in the initial genesis of the ANCA autoimmune response and be part of a multi-hit immunopathogenic mechanism.

The views expressed are those of the author and do not reflect the official policy of the Department of Army, Department of Defense, or U.S. Government.

Funding

• NIDDK Support