What is the significance of Extractable Nuclear Antigen (ENA) levels?

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Last updated: February 25, 2025 • View editorial policy

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From the Guidelines

ENA levels are crucial for diagnosing and managing autoimmune disorders, particularly Systemic Lupus Erythematosus (SLE), as they indicate the presence of autoantibodies targeting specific nuclear proteins. The significance of ENA levels lies in their ability to help clinicians diagnose conditions like SLE, Sjögren's syndrome, mixed connective tissue disease, and polymyositis/dermatomyositis 1. When ENA levels are elevated, they can indicate the presence of autoantibodies targeting specific nuclear proteins, such as chromatin, ribosomal P protein, spliceosome small nuclear ribonucleoproteins (Smith), Sjögren syndrome type A antigen (Ro), Sjögren syndrome type B antigen (La), and U1-ribonucleoprotein.

Some key points to consider when interpreting ENA levels include:

  • The ENA panel typically includes antibodies to specific antigens such as SS-A/Ro, SS-B/La, Sm, RNP, Scl-70, and Jo-1, each associated with different autoimmune conditions.
  • Anti-Sm antibodies are highly specific for SLE, while anti-Jo-1 antibodies are associated with polymyositis.
  • The pattern and level of these antibodies help determine the specific diagnosis, predict disease course, and guide treatment decisions.
  • ENA testing is particularly valuable when clinical symptoms suggest an autoimmune disorder but other tests like ANA (Antinuclear Antibody) screening provide insufficient diagnostic clarity, as recommended by an expert panel in 2023 1.
  • Regular monitoring of ENA levels may also help track disease activity and treatment response in some patients, though this varies by specific antibody and condition.

In terms of clinical application, elevated ENA levels should prompt further evaluation and consideration of autoimmune disorders, particularly SLE, and guide treatment decisions accordingly 1. By considering the pattern and level of ENA antibodies, clinicians can provide more accurate diagnoses and effective management plans for patients with autoimmune disorders.

From the Research

Significance of Extractable Nuclear Antigen (ENA) Levels

  • ENA levels are significant in the diagnosis and monitoring of various autoimmune diseases, including systemic lupus erythematosus (SLE) 2, 3, 4.
  • The detection of autoantibodies to ENA is indispensable in SLE, and the Bioplex 2200 ANA screen is a multiplex immunoassay system that allows simultaneous determination of autoantibodies to ENA 2.
  • ENA-6 profile by ELISA immunoassay has been evaluated in patients with SLE, and the results revealed that all of these ENA-6 and Sm antibodies as biomarkers complement diagnoses of active SLE 3.
  • Longitudinal tracking of ENA antibodies in a quaternary hospital laboratory cohort revealed dynamic antibody profiles, and changes in anti-ENA levels correlated with erythrocyte sedimentation rate and disease activity 4.
  • ENA reactivity has been detected in some patients with autoimmune hepatitis (AIH), even in the absence of ANA, and may characterize a particularly severe form of the disease 5.
  • An automated ENA screening assay (EliA Symphony) has been clinically evaluated for the screening of connective tissue diseases (CTD), and the results demonstrated that it has an efficiency similar to HEp-2 cells IIF for the diagnosis of CTD 6.

Clinical Utility of ENA Levels

  • The measurement of ENA levels can help in the diagnosis and differentiation of various autoimmune diseases, including SLE, mixed connective tissue disease (MCTD), and undifferentiated CTD (UCTD) 2, 3.
  • ENA levels can also be used to monitor disease activity and response to treatment in patients with autoimmune diseases 4.
  • The detection of ENA reactivity can help in the identification of patients with a particularly severe form of AIH 5.
  • The use of automated ENA screening assays can improve the efficiency and accuracy of diagnosis and monitoring of autoimmune diseases 6.

Correlation with Disease Activity

  • Changes in anti-ENA levels have been correlated with erythrocyte sedimentation rate and disease activity in patients with autoimmune diseases 4.
  • ENA reactivity has been detected in patients with AIH, and may characterize a particularly severe form of the disease 5.
  • The measurement of ENA levels can help in the monitoring of disease activity and response to treatment in patients with autoimmune diseases 4.

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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