Test Code #

047

CPT Code(s) #

86038, 86039, 86255, 86235 x5

Test Name

Systemic Sclerosis Panel (includes ANA, U1RNP, RNP70, Scl-70, CENP, RNA Polymerase III)

If Profile, Includes Tests:

N/A

Disease Name:

Systemic Sclerosis, Scleroderma

Type of Study:

Serum Studies

Methodology:

Indirect Immunofluorescence (HEp-2) and Fluoroenzyme immunoassay (FEIA)

Substrate:

N/A

Reference Range:

ANA (Titer)
• Negative <40

U1RNP (U/mL)
• Negative <5
• Equivocal 5-10
• Positive >10

RNP70 (U/mL)
• Negative <7
• Equivocal 7-10
• Positive >10

Scl-70 (U/mL)
• Negative <7
• Equivocal 7-10
• Positive >10

CENP (U/mL)
• Negative <7
• Equivocal 7-10
• Positive >10

RNA Polymerase III (U/mL)
• Negative <7
• Equivocal 7-10
• Positive >10

Units:

Titer, Units/mL

Schedule:

Assay performed once per week. Report availability is within one week from the time of specimen receipt.

Specimen Requirements:

Collect 5-10 ml of blood in a red top or serum separator tube. If possible, separate serum from clot and place into red capped tube provided with Beutner Laboratories collection kits. If separation facilities are not available, the blood can be sent in the tube used for collection.

Sample Stability:

Stable at ambient temperature during shipment. If sample is stored prior to shipment, it is stable refrigerated (2-8ºC) up to five days and frozen (-20ºC or lower) up to one year.

Clinical Relevance:

Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis, vasculopathy, and autoimmunity. Multiple organs can be involved, and various autoantibodies may be detected in sera of patients with SSc. Hep-2 IIF is a good screening assay for SSc, given its high sensitivity. The centromere pattern (specific for CENP-B antibodies) is highly associated with SSc and a lesser extent, also the nucleolar pattern. Topoisomerase I (Scl 70), centromere (CENPB), and RNA polymerase III are the three most frequent autoantigens recognized in SS. Other SSc-associated antibodies include antibodies to Ro/SSA (mainly 52 kDa subunit, in 15-19% patients),  fibrillarin (U3 RNP, in 1.4-8% patients), PM/Scl ( in 3-13% patients), Th/To (in 0.2-3.4% patients), and NOR90 (in 6% patients) all of these give a nucleolar pattern by IIF on HEp-2. ANAs are not useful for follow-up in SSc as they remain positive whatever the disease activity. Anti-Scl70 antibodies are detected in 30-40% of SSc sera with an estimated sensitivity of 43% and specificity of about 90%. The associated pattern on Hep-2 cells is speckled and nucleolar. These antibodies are associated with diffuse systemic sclerosis and with a higher risk of pulmonary fibrosis. Anti-centromere (CENP-B) antibodies are associated with limited SSc and with a higher risk of developing pulmonary hypertension. These antibodies are detected in 28-37% of patients with SSc and have a sensitivity of about 44% and specificity of 93%. Anti-RNA polymerase antibodies are associated with diffuse SSc and with a higher risk of scleroderma renal crisis. These are characterized by fine speckled pattern on Hep-2 cells. The antibodies are detected in 3.8-19.4% of patients with SSc with a sensitivity of 38% and specificity of about 94%. Anti-U1-RNP antibodies are found in about 5% of patients with SSc and are associated with a limited form of the disease and with a higher risk of pulmonary hypertension. These antibodies give a coarse speckled pattern on Hep-2 cells by IIF. Anti-U3-RNP antibodies are distinguished by a clumpy nucleolar pattern on Hep-2 cells and are detected in 1.5-8% of patients with SSc. These are associated with rapidly progressive disease.

Selected References:

Bossuyt, X., De Langhe, E., Borghi, M. O., & Meroni, P. L. Understanding and interpreting antinuclear antibody tests in systemic rheumatic diseases. Nature Reviews Rheumatology. 2020; 16(12): 715-726.

Didier K, Bolko L, Giusti D, Toquet S, Robbins A, Antonicelli F, Servettaz A. Autoantibodies Associated With Connective Tissue Diseases: What Meaning for Clinicians? Front Immunol. 2018 Mar 26;9:541.

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