What Are Lupus Cells and Are They Still Used for Diagnosis?

A lupus erythematosus cell, known as an LE cell, is a white blood cell that has ingested the nucleus of another, damaged cell. This phenomenon was first observed in the bone marrow of patients with systemic lupus erythematosus (SLE) in 1948 by Dr. Malcolm Hargraves. An LE cell is a neutrophil or macrophage—both are phagocytic cells that can engulf other particles—that has enveloped this altered nuclear material. Its discovery was one of the first biological indicators for SLE, providing a clue to the autoimmune nature of the disease.

The Biological Formation Process

The formation of a lupus erythematosus (LE) cell begins with damage to a cell through apoptosis, or programmed cell death. In individuals with systemic lupus erythematosus (SLE), this process releases nuclear material from the dying cell. This material, including DNA and associated proteins, is normally cleared away without incident. In lupus, however, the immune system mistakenly identifies this self-derived nuclear material as a foreign threat.

This misidentification triggers the production of autoantibodies, which are antibodies that target the body’s own tissues. These autoantibodies, particularly antinuclear antibodies (ANA), then coat the exposed nuclear fragments. This coating process, called opsonization, flags the nuclear material for destruction. It creates a complex of nuclear antigen and antibody that is recognizable to other immune cells.

Following opsonization, a phagocytic cell, such as a neutrophil, identifies the antibody-coated nucleus. The phagocyte engulfs this complex, forming an inclusion within its cytoplasm. This resulting cell—a phagocyte containing the remnant of another cell’s nucleus—is what pathologists identify as an LE cell. The ingested material, known as an LE body, appears as a uniform, purplish mass when stained and viewed under a microscope.

Detecting Lupus Cells in the Lab

The detection of LE cells is accomplished through a laboratory procedure known as the LE cell test or LE prep. This test is performed in vitro, meaning it occurs in a controlled environment outside the body, using a patient’s blood sample. The goal is to intentionally induce the formation of LE cells if the necessary biological components are present in the patient’s blood.

To begin the test, a blood sample is collected and mechanically agitated. Methods include stirring the blood with glass beads or pushing a clotted sample through a fine mesh screen. This trauma is designed to damage some white blood cells, causing them to rupture and release their nuclear material.

The sample is then incubated at 37°C to allow time for immunological reactions to occur. If the patient’s serum contains the antinuclear autoantibodies associated with lupus, these antibodies will bind to the newly exposed nuclei. Intact phagocytes present in the sample will then recognize and engulf these antibody-coated nuclei. After incubation, the blood is processed to concentrate the white blood cells, which are smeared onto a slide, stained, and examined microscopically to identify LE cells.

Historical and Current Diagnostic Role

When the LE cell was first discovered, its identification was a major advance in medicine. For the first time, clinicians had a laboratory marker strongly associated with systemic lupus erythematosus (SLE). The LE cell test became a primary tool for diagnosis, offering scientific evidence that had previously been unavailable. The presence of these cells in a patient’s blood was considered a strong indicator of SLE.

Despite its historical importance, the LE cell test is now considered obsolete and is rarely performed in modern diagnostics. Its decline is due to limitations in its performance. The test has low sensitivity, meaning it fails to detect the LE cell in a substantial portion of individuals who have lupus. The test may be positive in only 50% to 75% of people with acute SLE, leading to many false negatives.

The LE cell test also lacks specificity. While strongly associated with lupus, the cells can be found in patients with other autoimmune conditions, such as rheumatoid arthritis, or in those taking medications that induce a lupus-like syndrome. The test is also labor-intensive and its interpretation can be subjective. These factors led to its replacement by more reliable methods, shifting the LE cell to a finding of historical interest.

Comparison to Modern Lupus Blood Tests

The LE cell test has been superseded by more advanced and reliable blood tests for diagnosing systemic lupus erythematosus (SLE). The primary of these is the Antinuclear Antibody (ANA) test. The ANA test is the standard screening tool because of its high sensitivity; approximately 98% of people with systemic lupus will have a positive ANA result. This test detects autoantibodies that target components within a cell’s nucleus, the same issue that leads to LE cell formation. A negative ANA test makes a lupus diagnosis very unlikely.

While the ANA test is excellent for screening, a positive result is not conclusive, as it can be positive in other autoimmune diseases and even in some healthy individuals. If the ANA test is positive, physicians will order a panel of more specific autoantibody tests to confirm a lupus diagnosis. These include tests for anti-double-stranded DNA (anti-dsDNA) and anti-Smith (anti-Sm) antibodies.

The presence of anti-dsDNA and anti-Sm antibodies is highly specific to lupus. Unlike the LE cell test, which provides a qualitative result, these modern tests can be quantitative, measuring the antibody level in the blood. Elevated levels of anti-dsDNA antibodies, for instance, can correlate with disease activity, particularly with kidney involvement, a serious complication of lupus. This evolution in testing provides a more detailed and accurate picture of a patient’s immune status.

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