No abstract

Objective Many Native American ( NA ) patients with systemic lupus erythematosus ( SLE ) do not exhibit the classical SLE autoantibody profiles of European American ( EA ) and African American ( AA ) patients with SLE . The poorer SLE disease outcomes noted in NA patients highlights a need for more equitable diagnostic and prognostic tools for NA patients with SLE . The objective was to identify informative autoantibody profiles for NA , AA , and EA patients with SLE using an expanded set of autoantigens. Methods Sera from 49 NA , 49 AA , and 49 EA age‐, sex‐, and antinuclear autoantibody titer–matched patients with SLE who met the American College of Rheumatology classification criteria and 10 ethnicity‐, sex‐, and age‐matched controls were tested for autoantibody reactivity by autoantigen microarrays. Autoantibodies that were significantly elevated in patients with SLE compared with ethnicity‐specific controls were selected for hierarchical clustering. Differences in clinical criteria between patient clusters were determined by Fisher's exact test and corrected for multiple comparisons. Results NA , AA , and EA patients with SLE each had a cluster distinguished by higher levels of anti‐Ro52 and another cluster distinguished by nucleic acid–specific autoantibodies. Additional clusters were distinguished in NA patients by elevated extracellular matrix autoantibodies and were distinguished in AA patients by elevated Sm/ RNP autoantibody and elevated nucleolin/histone autoantibody. Two EA patient clusters with similar nucleic acid– and Ro52‐specific autoantibodies were distinguished by either high or low histone 2A reactivity. Renal manifestations trended higher in the NA Ro52 cluster and were significantly enriched in the AA nucleolin/histone cluster. The AA nucleolin/histone cluster and EA H2A cluster had higher disease activity. Conclusion Expanded autoantibody profiles can identify informative subsets of patients with SLE .

No abstract

BackgroundAutoantibodies (AAbs) are a hallmark of systemic lupus erythematosus (SLE). Common SLE AAbs show differences in specificities, levels and associations with clinical characteristics of disease which may be influenced by ethnicity.(1-2) NA SLE patients do not always exhibit classical AAb profiles.(2) Understanding how AAb profiles associate with clinical disease, including in NA patients, is important to better inform disease management.ObjectivesTo identify patient subsets enriched for renal disease by clustering NA, AA and EA SLE patients into more homogeneous disease subsets based on expanded AAb profiles.MethodsSerum samples from 49 NA, 49 AA, and 49 EA age, sex and ANA titer-matched SLE patients who met ACR classification and 10 sex and age matched controls from each ethnicity were tested for AAb reactivity by autoantigen microarray. Normalized fluorescence intensity (NFI) for AAb binding was determined for each individual for all autoantigens. Ratios of NFIs to total IgG were calculated and converted to Z-scores. Kruskal-Wallis analysis of Z-score transformed AAb ratios were used to identify AAbs that differed significantly between patients and controls for each ethnicity; these AAbs were used for hierarchal clustering of SLE subjects within each ethnicity. The enrichment of SLE clinical criteria within each cluster was determined by Fisher’s exact test.ResultsAAbs to nucleic acids and Ro52 were present in SLE patients of all three ethnicities. On average, NA SLE patients, but not EA or AA SLE patients, had lower levels of AAbs against extracellular matrix (ECM) antigens compared to controls. AA and EA, but not NA, SLE patients had significantly higher levels of AAbs to Sm, RNP and histones compared to matched controls. In each ethnicity four clusters of SLE subjects were identified by ethnicity-specific AAbs. All three groups had a cluster of subjects enriched in nucleic acid-specific AAbs and a cluster of subjects enriched in Ro52 AAbs. The NA group also had two clusters enriched in ECM AAbs. The AA group had an Sm/RNP AAb enriched cluster and a nucleolin/histone AAb enriched cluster. Two additional EA SLE clusters had similar levels of nucleic acid-specific AAbs and Ro52 AAbs, but were distinguished by significant differences in histone 2A (H2A) AAb levels. Renal manifestations were significantly enriched in the NA Ro52 cluster and the AA nucleolin/histone cluster compared to other SLE patient clusters of the same ethnicity.Abstract THU0263 – Figure 1ConclusionExpanded AAb profiles can be used to identify SLE subsets that are more likely to have renal manifestations of disease.References[1] Sánchez E, et al. Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian-European populations. Arthritis Rheum. 2012;64(11):3687-94.[2] Kheir JM, et al. Unique clinical characteristics, autoantibodies and medication use in Native American patients with systemic lupus erythematosus. Lupus Sci. & Med. 2018;5:e000247.AcknowledgementThis ...