694 - Positive Predictive Value of Anti-Centromere and Anti-Scl-70 Antibody Multiplex Assays in a Rheumatology Practice Setting

Sunday, November 6, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Svetlana Meier, Univ of Nebraska Med Center, Omaha, NE and Ted R. Mikuls, Omaha VA and University of Nebraska, Omaha, NE
Presentation Number: 694

Background/Purpose: 

Recent concerns have been raised regarding the sensitivity of multiplex ANA testing compared to ‘gold-standard' methods involving Hep2A substrate by immunoflourence (IF).  There has been less attention given to the predictive values of antibodies targeting specific nuclear antigens incorporated in the multiplex approach, specifically with regards to anti-centromere and anti-SCL-70 positivity that have had high specificity with conventional assays in the past.  The aim of this study was to determine the positive predictive value (PPV) of anti-centromere and anti-SCL-70 antibody multiplex assays in a rheumatology practice setting and to characterize patients with false-positive results using this approach. 

Method:

As part of a retrospective medical record review, we identified patients seen in an academic rheumatology practice between January 2008 and January 2010 and with positive test results for either anti-centromere or anti-Scl-70 antibody.  As a gold-standard, we categorized patients based on the receipt of a formal connective tissue disease (CTD) diagnosis from a board certified rheumatologist or satisfaction of distinct ACR CTD classification criteria available (with a focus on classification criteria for systemic sclerosis – both limited and diffuse forms).  Alternative CTD diagnoses, other health conditions and comorbid illnesses were documented.

Result:

There were 73 patients seen over the two-year study period with positive tests for either anti-centromere (n = 47) or anti-SCL-70 (n = 23) (See Table).  All patients were examined by a board certified academic rheumatologist.  Of the 47 patients who had a positive anti-Scl-70 antibody and were evaluated by a rheumatologist, 2 patients had a diagnosis of diffuse systemic sclerosis and 1 patient had a diagnosis of CREST syndrome, yielding a PPV of only 6.4%.  Among patients not meeting criteria for scleroderma and who were anti-SCL-70 positive, 4 were diagnosed with liver cirrhosis or autoimmune hepatitis, 5 had a positive Raynaud's phenomenon without any other CTD manifestations, 6 had SLE complicated by glomerulonephritis, and 2 were diagnosed with RA.  Of the 26 patients who were positive for anti-centromere antibodies, 8 patients had a diagnosis of CREST syndrome, yielding a PPV of 30.7%.  Additionally, 7 had liver disease, 2 had Raynaud's phenomenon in the absence of other CTD manifestations, 1 had an SLE, and 1 RA. 

 

Test

Diffuse scleroderma

Limited scleroderma (CREST)

Liver disease

Raynaud's

phenomenon

SLE

 

RA

Anti-Scl-70 (+), n=47

 2

 1

4

5

6

2

Anti-centromere (+), n=26

 0

 8

7

2

1

1

Conclusion: 

In contrast to prior reports examining the diagnostic characteristics of anti-centromere and anti-SCL-70 using conventional laboratory methods, false positive results are frequently observed using the newer solid-phase multiplex approach.  Chronic liver disease, primary Raynaud's phenomenon, SLE, and RA emerged as frequent underlying conditions among rheumatology patients with false-positive results.

 


Keywords: anti-centromere antibodies (ACA)

Disclosure: S. Meier, None; T. R. Mikuls, None.