Comparison of autoantibody specificities between traditional and bead‐based assays in a large, diverse collection of patients with systemic lupus erythematosus and family members

Bruner, Benjamin F.; Guthridge, Joel M.; Lu, Rufei; Vidal, Gabriel; Kelly, Jennifer A.; Robertson, Julie M.; Kamen, Diane L.; Gilkeson, Gary S.; Neas, Barbara R.; Reichlin, Morris; Scofield, R. Hal; Harley, John B.; James, Judith A.

doi:10.1002/art.34651

Cited by 80 publications

(79 citation statements)

References 74 publications

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“…A previous study conducted in Taiwan indicated that the positivity rate of ANA in patients with SLE was over 90% [17]. According to the study by Wichainun et al [18], the ANA test has a sensitivity of over 90% to detect SLE, which is considerably higher than those from other autoantibodies such as anti-dsDNA and anti-SSA/SSB [19]. Therefore, ANA test is a test of choice for initial screening of SLE among patients with multisystemic disorders.…”

Section: Discussionmentioning

confidence: 99%

Patterns of Ambulatory Medical Care Utilization and Rheumatologist Consultation Predating the Diagnosis of Systemic Lupus Erythematosus: A National Population-Based Study

et al. 2014

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ObjectiveTo investigate the records of ambulatory medical care from patients predating the diagnosis of systemic lupus erythematosus (SLE) using nationwide, population-based claims data.MethodsThe frequencies and costs of ambulatory medical care utilization in 337 newly-diagnosed SLE cases between 2004 and 2010, identified from Taiwan's National Health Insurance Research Database, were compared with 1,348 controls who were frequency matched for sex, age, and the catastrophic illness certificate application year of the cases.ResultsPatients with SLE had a median frequency of ambulatory medical care utilization compared with controls one year prior to the index date (22 vs. 2, P<0.001). The differences were significant throughout all eight annual periods. Similarly, the inflation-adjusted costs of ambulatory medical care utilization in patients with SLE increased annually over the study period, from a median of US$18 eight years prior to the index date to US$680 one year prior to the index date. Diseases of the respiratory system (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 460–519), digestive system (ICD-9-CM codes 520–579), musculoskeletal system and connective tissue (ICD-9-CM codes 710–739, excluding 710.0), and skin and subcutaneous tissue (ICD-9-CM codes 680–709) were the top four common causes of visits in the 0.5 to 2 year period preceding the index date and percentages of SLE patients suffered from these disorders increased progressively over the study period. Only 56.4% of the patients with SLE had consulted a rheumatologist and most of the serology tests were done within one year predating the index date.ConclusionsIncreased frequencies and costs of ambulatory care utilization among Taiwanese patients with SLE occurred several years predating their definitive SLE diagnosis. When multisystemic disorders are presented in young female patients, the possibility of SLE should be considered and screened with tools such as the antinuclear antibody test.

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Section: Discussionmentioning

confidence: 99%

Patterns of Ambulatory Medical Care Utilization and Rheumatologist Consultation Predating the Diagnosis of Systemic Lupus Erythematosus: A National Population-Based Study

et al. 2014

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“…Autoantibodies to dsDNA, chromatin, Ro/Sjögren's-syndrome-related antigen A (SSA), La/SSB, Sm, SmRNP complex and ribonucleoprotein (RNP) were detected using the xMAP BioPlex 2200 multiplex system (Bio-Rad Technologies, Hercules, California, USA) 16. WISH Reporter cells (CAT# CCL125; ATCC) were used to measure the ability of sera to induce type I IFN-related gene transcription 6.…”

Section: Methodsmentioning

confidence: 99%

Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification

et al. 2016

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Objectives The relationship of immune dysregulation and autoantibody production that may contribute to systemic lupus erythematosus (SLE) pathogenesis is unknown. This study evaluates the individual and combined contributions of autoantibodies, type I interferon (IFN-α) activity, and IFN-associated soluble mediators to disease development leading to SLE. Methods Serial serum specimens from 55 individuals collected prior to SLE classification (average timespan = 4.3 years) and unaffected healthy controls matched by age (± 5 years), gender, race, and time of sample procurement were obtained from the Department of Defense Serum Repository. Levels of serum IFN-α activity, IFN-associated mediators, and autoantibodies were evaluated and temporal relationships assessed by growth curve modeling, path analysis, Analysis of Covariance, and random forest models. Results In cases, but not matched controls, autoantibody specificities and IFN-associated mediators accumulated over a period of years, plateauing near the time of disease classification (p<0.001). Autoantibody positivity coincided with or followed type II IFN dysregulation, preceding IFN-α activity in growth curve models, with elevated IFN-α activity and BLyS levels occurring shortly before SLE classification (p≤0.005). Cases were distinguished by multivariate random forest models incorporating IFN-γ, MCP-3, anti-chromatin and anti-spliceosome antibodies (accuracy 93% > 4 years pre-classification; 97% within 2 years of SLE classification). Conclusions Years before SLE classification, enhancement of the type II IFN pathway allows for accumulation of autoantibodies and subsequent elevations in IFN-α activity immediately preceding SLE classification. Perturbations in select immunological processes may help identify at-risk individuals for further clinical evaluation or participation in prospective intervention trials.

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“…7 Autoantibody specificities were compared using a multiplexed, bead-based assay (BioPlex 2200, Bio-Rad, Hercules, California, USA) that simultaneously detects dsDNA, chromatin, ribosomal P, Ro/SSA (60 and 52 kDa), La/SSB, Sm, SmRNP complex, RNP, centromere B, Scl-70 and Jo-1 autoantibodies. 8 Anti-dsDNA is reported in IU/mL with a manufacturer-specified positive cut-off of 10.0 IU/mL, and other specificities as an Antibody Index (AI) value (range 0-8) based on the fluorescence intensity of each of the other autoantibody specificities, with a manufacturer-recommended positive cut-off of AI=1.0. 8…”

Section: Autoantibody Detectionmentioning

confidence: 99%

Use of SLICC criteria in a large, diverse lupus registry enables SLE classification of a subset of ACR-designated subjects with incomplete lupus

et al. 2017

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ObjectiveSLE is traditionally classified using the American College of Rheumatology (ACR) criteria. The Systemic Lupus International Collaborating Clinics (SLICC) recently validated an alternative system. This study examined large cohorts of subjects with SLE and incomplete lupus erythematosus (ILE) to compare the impact of ACR and SLICC criteria.MethodsMedical records of subjects in the Lupus Family Registry and Repository were reviewed for documentation of 1997 ACR classification criteria, SLICC classification criteria and medication usage. Autoantibodies were assessed by indirect immunofluorescence (ANA, antidouble-stranded DNA), precipitin (Sm) and ELISA (anticardiolipin). Other relevant autoantibodies were detected by precipitin and with a bead-based multiplex assay.ResultsOf 3575 subjects classified with SLE under at least one system, 3312 (92.6%) were classified as SLE by both systems (SLEboth), 85 only by ACR criteria (SLEACR-only) and 178 only by SLICC criteria (SLESLICC-only). Of 440 subjects meeting 3 ACR criteria, 33.9% (149/440) were SLESLICC-only, while 66.1% (n=291, designated ILE) did not meet the SLICC classification criteria. Under the SLICC system, the complement criterion and the individual autoantibody criteria enabled SLE classification of SLESLICC-only subjects, while SLEACR-only subjects failed to meet SLICC classification due to the combined acute/subacute cutaneous criterion. The SLICC criteria classified more African-American subjects by the leucopenia/lymphopenia criterion than did ACR criteria. Compared with SLEACR-only subjects, SLESLICC-only subjects exhibited similar numbers of affected organ systems, rates of major organ system involvement (∼30%: pulmonary, cardiovascular, renal, neurological) and medication history.ConclusionsThe SLICC criteria classify more subjects with SLE than ACR criteria; however, individuals with incomplete lupus still exist under SLICC criteria. Subjects who gain SLE classification through SLICC criteria exhibit heterogeneous disease, including potential major organ involvement. These results provide supportive evidence that SLICC criteria may be more inclusive of SLE subjects for clinical studies.

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Comparison of autoantibody specificities between traditional and bead‐based assays in a large, diverse collection of patients with systemic lupus erythematosus and family members

Cited by 80 publications

References 74 publications

Patterns of Ambulatory Medical Care Utilization and Rheumatologist Consultation Predating the Diagnosis of Systemic Lupus Erythematosus: A National Population-Based Study

Patterns of Ambulatory Medical Care Utilization and Rheumatologist Consultation Predating the Diagnosis of Systemic Lupus Erythematosus: A National Population-Based Study

Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification

Use of SLICC criteria in a large, diverse lupus registry enables SLE classification of a subset of ACR-designated subjects with incomplete lupus

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