Session Title: Miscellaneous Rheumatic and Inflammatory Diseases Poster II
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Circulating autoantibodies precede clinical onset of several autoimmune diseases. The characteristics of the so-called pre-clinical stage of autoimmune diseases are poorly understood. Anti-mitochondria autoantibodies (AMA) occur in >95% Primary Biliary Cholangitis (PBC) patients. AMA-positive subjects with normal liver enzymes are occasionally suspected in the indirect immunofluorescence (IIF) assay on HEp-2 cells and further confirmed on specific AMA assays. The liver histological status in biochemically normal (BN) AMA-positive individuals (BN/AMA) is not determined. The Enhanced Liver Fibrosis (ELF) score is a surrogate marker for assessing liver fibrosis state. We prospectively followed-up the autoantibody response, serum liver enzymes and ELF score in AMA/BN and PBC patients along a 7-year period.
Methods: 327 samples from 35 PBC patients and 59 BN/AMA were prospectively obtained along an average interval of 4.09 (range: 0.50–7.10) and 3.59 (0.50–7.40) years, respectively. Samples were tested by IIF on rat kidney (IIF-AMA), western blot with rat liver (WB-AMA) and ELISA for PBC-associated autoantibodies against pyruvate dehydrogenase (anti-PDC-E2), nuclear envelope protein gp210, protein sp100, and centromeric proteins CENP-A/B. Anti-PDC-E2 avidity was determined by 6M urea-elution modified ELISA. Alkaline phosphatase (ALP), gamma glutamyl transferase (ɣGT) and ELF score were measured by automated methods.
Results: PBC patients had higher ELF score (p<0.001), ALP (p <0.001), ɣGT (p<0.001), and anti-PDC-E2 (p<0.001) serum levels, as well as higher anti-PDC-E2 avidity (p=0.022) than BN/AMA. Along the follow-up, there was an increase in anti-PDC-E2 (p<0.001) and IIF-AMA (p<0.001) serum levels in BN/AMA, but not in PBC patients. There was increase in anti-PDC-E2 avidity (p<0.001) and ELF score (p<0.001) in both groups. There was a positive temporal correlation between: 1) ELF score and anti-PDC-E2 levels in BN/AMA (r=0.239; p<0.001) and in PBC patients (r=0.268; p=0.004); 2) ELF score and IIF-AMA in BN/AMA (r=0.465; p<0.001); and 3) ELF score and anti-PDC-E2 avidity in PBC (r=0.341; p<0.001). Along time, there was an increase in the number of recognized autoantigen targets in 39% BN and 49% PBC patients. BN/AMA depicted four divergent patterns of longitudinal behavior regarding anti-PDC-E2 serum levels and ELF score: ascending, descending, stable and erratic.
Conclusion: Along time, AMA/BN asymptomatic individuals undergo progressive expansion and intensification in the humoral autoimmune response. This process correlates with increase in serum liver fibrosis biomarkers indicating an ongoing silent inflammatory process in the liver. This represents an opportunity case for early therapeutic intervention and prevention of development of autoimmune diseases. However, there is heterogeneity in the longitudinal behavior among AMA/BN individuals, and not all AMA/BN individuals may evolve to overt PBC.
To cite this abstract in AMA style:Baldo D, Dellavance A, Ferraz ML, Andrade LEC. Autoantibodies As Biomarkers for the Identification of Pre-Clinical Stages of Autoimmune Diseases: Demonstration of Inflammatory and Fibrotic Activity in the Liver of Asymptomatic and Biochemically Normal Individuals with Anti-Mitochondria Antibodies [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/autoantibodies-as-biomarkers-for-the-identification-of-pre-clinical-stages-of-autoimmune-diseases-demonstration-of-inflammatory-and-fibrotic-activity-in-the-liver-of-asymptomatic-and-biochemically-no/. Accessed May 10, 2021.
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