Background/Purpose : Our objective was to prospectively establish
the performance characteristics of a cell bound complement activation products (CB-CAPS)
in a multi-analyte assay with algorithm (MAAA) laboratory test currently
offered in the United States as decision tool assisting rheumatologists with
the differential diagnosis of systemic lupus erythematosus (SLE).

Methods : The population of subjects enrolled in this
validation cohort consisted of 75 consecutive primary fibromyalgia syndrome
(FMS) (96% females, mean age 48 years) and 75 consecutive adult SLE (88%
females, mean age 53 years). All subjects fulfilled their respective American
College of Rheumatology classification criteria of disease. The subjects were enrolled
at two rheumatology practices located in Southern California, and each patient
provided informed consent following appropriate Ethic Committees approval. Venous
blood was collected and shipped overnight to our reference clinical laboratory
conducting routine diagnostic immunology testing for CB-CAPS (erythrocyte and B-lymphocyte
C4d) and other autoimmune markers including antinuclear antibodies (ANA) as
determined using solid phase assay and indirect immunofluorescence (IIF), anti-dsDNA
antibodies (all confirmed by Crithidia Luciliae IIF) and additional cellular autoantibodies. The
CB-CAPS in MAAA combining these autoimmune markers relies on two consecutive
tiers of analysis as currently approved by the Department of Health in the
State of NY and reported as positive or negative. Test performances in this
validation cohort were assessed using sensitivity, specificity, positive and
negative likelihood ratio (LR). Post-test probability of SLE disease versus primary
fibromyalgia was determined using standard 20% prior probability. All testing laboratory
personnel were blinded to subject diagnosis during the pre-analytical,
analytical and post-analytical phase of testing.

Results : ANA was positive in 33% FMS (67%
specific) and was 80% sensitive for SLE (LR+=2.8). Anti-dsDNA was negative in
all FMS (100% specific) but yielded low sensitivity in SLE (17%; LR+>13). High
CB-CAPs as defined by EC4d or BC4d levels above the 95^th percentile
established among normal healthy individuals were infrequently detectable among
FMS patients (4% positives, 96% specificity) but were detectable in 60% SLE (LR+>43)(Table).
Using these performances characteristics, a positive CB-CAPS in MAAA assessment
would raise the probability (post-test) for SLE compared to FMS from 20%
(pre-test) to higher than 92%. Conversely, a negative CB-CAPS in MAAA test
result would reduce the post-test probability of SLE from 20% to 9%.

Conclusion : Our data indicate that CB-CAPS in MAAA can
distinguish FMS from SLE.

Table: Positive and negative
Likelihood ratio and post-test probabilities of SLE and Fibromyalgia