Background/Purpose : Clinicians are aware that the
interpretation of any clinical diagnostic test and post-test probability of
disease is highly influenced by pre-test probability or prevalence of the
condition in which the test result is used. We have recently established that a
group of primary fibromyalgia and systemic lupus erythematosus (SLE) patients
can be distinguished by anti-dsDNA and cell bound complement activation
products (CB-CAPS) in multi-analyte assay (MAAA) panel. The purpose of this study
was to translate these findings in the context of patients evaluated for SLE or
another mimicking disease by community based rheumatologists in the United
States.

Methods : From February 2014 to May 2015, a total of 35,792 CB-CAPS
in MAAA panels were requested by 902 physicians during the course of clinical diagnostic
care of 35,792 patients (mean ± SD 51±15 years, 84% females). Venous blood was
collected from all patients and shipped to our NY/CAP accredited centralized laboratory
conducting routine testing for CB-CAPS (erythrocyte and B-lymphocyte C4d) plus
a panel of diagnostic immunology markers including anti-nuclear antibodies (ANA)
and anti-double stranded DNA antibodies. Abnormal CB-CAPs are defined by EC4d
or BC4d levels above the upper 95^th percentile of a group of normal
healthy individuals. CB-CAPS are combined with anti-dsDNA and other
anti-cellular antibodies in two consecutive tiers of analysis that produces a positive
or negative assessment reported to ordering clinicians. For the purpose of this
study, de-identified laboratory result assessments were extracted from our clinical
laboratory information system and analyzed in our population health data warehouse
system. Pre-test probability of SLE was estimated using the method developed by
Rogan and Gladen (Am J Epidemiol. 1978 107:71) that
uses sensitivity (Se), specificity (Sp), and positivity rate (R) for the
diagnostic: prevalence= [R – (1-Sp)]/(Se – (1-Sp)]. Predictive values of
positive test assessments (PPV) were derived from pre-test probability using
standard statistics.

Results : In this cohort of 35,792 patients, positivity rate of ANA
was 49%, anti-dsDNA 5.0%, CB-CAPS 10% and CB-CAPS in MAAA panel 14% (Table). Applying
the formula for estimation of SLE prevalence (pre-test probability) yielded
very similar rates from 16-20%. The predictive value of a positive test (PPV)
ranged from 59% to 86%. Furthermore CB-CAPS in MAAA positive test results identified
of a higher number of SLE patients (n=4259) than anti-dsDNA alone (n=1047),
with fewer false positive results.

Conclusion : These tests are being used by rheumatologists
appropriately in patient populations where the possibility of SLE is being
considered. In this context high CB-CAPs in MAA identified more true SLE
patients with fewer false positive results.

Table: Derivation of pre-test and post
probability of SLE in US rheumatology based practice