Expanded Autoantibody Profiles for Subsetting of Native American, African American, and European American Patients With Systemic Lupus Erythematosus

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 .

Serological abnormalities that predict progression to systemic autoimmune rheumatic diseases in antinuclear antibody–positive individuals

“…While the presence of autoAbs to a diverse array of nuclear and non-nuclear autoAgs has been previously noted in SLE [20,[27][28][29], here we show that this can also be seen in some ANA þ individuals lacking a SARD diagnosis. This finding indicates that a broad breach of B cell tolerance can be seen in the absence of clinical disease activity and raises the possibility that it results from the genetic polymorphisms that promote disease.…”

“…Previous studies have contrasted the performance of different immunoassay techniques to detect autoAbs in individuals with SARD [20,[27][28][29]. However, in general these studies have investigated their diagnostic utility in comparison with HCs, unaffected relatives and/or individuals with non-SARD musculoskeletal conditions [2,[30][31][32][33].…”

Autoantibodies spectrum in lupus nephritis in a cohort of Egyptian patients: relation to disease activity and prognostic value

“…Recently, there is a huge attention to the use of autoantibodies as a predictor of disease progression in early SLE, hoping to limit the morbidity and mortality [22]. Guthridge et al concluded that studying the ANA profile may have a prognostic value in SLE patients [23]. On studying the ANA profile in our patients, we found that anti-dsDNA, anti-nucleosome, anti-histone, anti-Ro60, and anti-Ro52 autoantibodies were implicated with the highest frequency, so we evaluated the alleged role for their use as biomarkers for SLE and their relationship with disease activity and renal affection.…”

Unique Serum Immune Phenotypes and Stratification of Oklahoma Native American Rheumatic Disease Patients

“…Major shortcomings exist in the identification and treatment of NA patients with rheumatic disease contributed by uncharacteristic clinical presentations in NA patients compared with those of White and African ancestry that define standard classification criteria (8,39). Furthermore, the heterogeneity and overlap of autoimmune disease symptomology pose significant challenges for diagnosis, treatment, research, and clinical trials.…”