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Test Code ANA CASCADE Connective Tissue Diseases Cascade, Serum

Additional Codes

Mayo Test ID
CTDC

Reporting Name

Connective Tissue Disease Cascade,S

Useful For

Evaluation of patients with signs and symptoms compatible with connective tissue diseases

 

Initial evaluation of patients in clinical situations in which the prevalence of disease is low (6)

 

This test is not recommended for:

-Testing in clinical situations in which there is a high prevalence of connective tissue diseases (eg, rheumatology specialty practice)

-Follow-up evaluation of patients with known connective tissue diseases

Profile Information

Test ID Reporting Name Available Separately Always Performed
ANA2 Antinuclear Ab, S Yes Yes
CCP Cyclic Citrullinated Peptide Ab, S Yes Yes
IM_01 Interpretation No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CMA Centromere Ab, IgG, S Yes No
CASMT ANA2 Cascade No No
RIB Ribosome P Ab, IgG, S Yes No
ENAE Ab to Extractable Nuclear Ag Eval,S Yes No
ADNA1 dsDNA Ab, IgG, S Yes No

Testing Algorithm

If antinuclear antibodies are greater than or equal to 3.0 U, then antibodies to double-stranded DNA (dsDNA), extractable nuclear antigen evaluation, ribosome P, and centromere are performed at an additional charge.

 

For more information see Connective Tissue Disease Cascade.

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Specimen Type

Serum


Specimen Required


Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

Collection Information: Centrifuge and aliquot serum into plastic vial.


Specimen Minimum Volume

0.7 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 21 days
  Frozen  21 days

Special Instructions

Reference Values

ANTINUCLEAR ANTIBODIES (ANA)

≤1.0 U (negative)

1.1-2.9 U (weakly positive)

3.0-5.9 U (positive)

≥6.0 U (strongly positive)

Reference values apply to all ages.

 

CYCLIC CITRULLINATED PEPTIDE ANTIBODIES, IgG

<20.0 U (negative)

20.0-39.9 U (weak positive)

40.0-59.9 U (positive)

≥60.0 U (strong positive) 

Reference values apply to all ages.

Day(s) Performed

Monday through Saturday

Test Classification

This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information

86038

86200

83516-Centromere (if appropriate)

83516-Ribosome (if appropriate)

86225-ds-DNA AB IgG, Serum (if appropriate)

86235 x 6-RNP, Sm, SS-B, SS-A, Jo 1, and Scl 70 (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
CTDC Connective Tissue Disease Cascade,S 95267-1

 

Result ID Test Result Name Result LOINC Value
ANA2 Antinuclear Ab, S 94875-2
CCP Cyclic Citrullinated Peptide Ab, S 33935-8
IM_01 Interpretation 69048-7

Clinical Information

The following diseases are often referred to as connective tissue diseases (CTD): rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis including CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia), Sjogren syndrome, mixed connective tissue disease, and idiopathic inflammatory myopathies. CTD (also known as systemic rheumatic diseases) are characterized by immune-mediated inflammation that involves the joints, skin, and visceral organs. These diseases are also accompanied by antibodies to a host of nuclear and cytoplasmic autoantigens.

 

The diagnosis of any CTD is based on clinical signs and symptoms and characteristic radiographic, histopathologic, and serologic findings. Certain CTD are characterized by autoantibodies that are highly specific for individual diseases as outlined in the Table. CTD often present clinically with signs and symptoms that are nonspecific, including constitutional signs such as fever, weight loss, fatigue, and arthralgias.

 

Table. Autoantibodies and Clinical Associations with Specific Connective Tissue Diseases

Cyclic citrullinated peptide antibodies

Rheumatoid arthritis

Double-Stranded DNA (dsDNA)

Systemic lupus erythematosus (SLE)

Smith (Sm)

SLE

Ribosome P

SLE

SS-B/La

Sjogren syndrome (SjS)

SS-A/Ro (Ro52 or Ro60)

SjS, SLE, systemic sclerosis (SSc), antisynthetase syndrome

RNP 68 and A (RNP)

Mixed connective tissue disease

Topoisomerase 1 (topo-1, Scl-70)

SSc

Histidyl tRNA synthetase (JO1)

Idiopathic inflammatory myositis (commonly anti-synthetase syndrome)

Centromere B

SSc (most commonly the limited cutaneous forms: LcSSc)

 

In this testing cascade, serum is tested initially for the presence of antinuclear antibodies (ANA) and for cyclic citrullinated peptide (CCP) antibodies. The presence of CCP antibodies indicates a strong likelihood of rheumatoid arthritis (RA).(1) However, additional testing for rheumatoid factor, which is not included in the cascade, is important for optimal diagnosis as per the 2010 American College of Rheumatology/European League Against Rheumatism RA classification criteria.(2) The presence of ANA supports the possibility of a CTD, and the level of ANA is used to identify sera for second-order testing for antibodies to dsDNA and the other autoantigens. The decision threshold for performing second-order tests is based on empirical data derived from testing patients with varying levels of ANA and is chosen to minimize testing in situations in which positive results for dsDNA and other antibodies is very unlikely.(3) However, a negative ANA enzyme immunoassay result does not rule out a diagnosis of CTD as has been reported in a number of studies. Therefore, in patients with a strong clinical suspicion of CTD, testing for ANA by indirect immunofluorescence assay may be warranted.(4,5)

Interpretation

Interpretive comments are provided.

 

See individual test IDs for additional information.

 

Differential testing for Ro52 and Ro60 antibodies in SS-A/Ro positive patients may be useful in the diagnosis of specific CTD clinical subset, disease stratification, and prognosis. Consider testing for Ro52 and Ro60 antibodies (ROPAN / Ro52 and Ro60 Antibodies, IgG, Serum) if the patient is positive for SS-A/Ro.

Cautions

The results of tests for autoantibodies must be interpreted in the appropriate clinical context.

 

The presence of detectable levels of antinuclear antibodies (ANA) in solid-phase immunoassays, such as enzyme-linked immunosorbent assay (ELISA), is not specific for connective tissue disease.

 

Positive results may occur prior to onset of clinical diseases as well as in the absence of connective tissue disease.

 

Negative ANA by ELISA results may not be reliable for the evaluation of patients at-risk for systemic sclerosis and inflammatory myopathies.

 

Weak-to-moderate positive results for cyclic citrullinated peptide antibodies may occur in patients with connective tissue diseases other than rheumatoid arthritis.

Report Available

3 to 4 days

Reject Due To

Gross hemolysis Reject
Gross lipemia Reject
Gross icterus OK

Method Name

Enzyme-Linked Immunosorbent Assay (ELISA)