Clinical History:

This patient is a 16-year-old girl who tells you that she was feeling well until about six months ago. At that time she noticed increasing fatigue and her ankles periodically swelled up. Her local physician did a routine physical examination and noted 2+ pitting edema of her ankles, but no other findings. A routine urinalysis showed 4+ proteinuria and red blood cells present, but no RBC casts. Further laboratory workup revealed that she had an elevated erythrocyte sedimentation rate (ESR), slight anemia with Hgb 11.2, slight leukopenia with total WBC count 3500, and normal serum chemistries except for a slightly decreased serum albumin (2.9 gm/dl). Her antinuclear antibody (ANA) was positive at 1:256 (normal <1:20). Her serum C3 complement level was decreased. You order a nephrology consult, and the nephrologist performs a renal biopsy.

Image 2.1:

The facial skin rash is shown here. Again, a "butterfly" rash is present.

Image 2.2:

This is the antinuclear antibody test pattern. The rounded bright green objects are the nuclei of reagent substrate to which the patient's serum has been added and stained with a fluorosceinated anti-human IgG. This is a typical positive ANA pattern. The "titer" is determined by staining serial dilutions of the patient serum and determining the greatest dilution (e.g., 1:64 or 1:256) at which positive staining is seen.

Image 2.3:

A positive LE cell test is shown here. A PMN surrounds a homogenous dark pink inclusion. This is a graphic demonstration of the body's reaction against "self" nuclear material, but it is not as sensitive a test as the ANA.

Image 2.4:

The renal biopsy is shown here by light microscopy (H&E stain). Note the thickening of the glomerular capillary loops. The loops are thick and pink and hardly a capillary lumen is left.

Image 2.5:

This glomerulus shows similar capillary loop thickening by light microscopy.

Image 2.6:

The granular immunofluorescence pattern in the glomerulus with anti-IgG is seen here. The staining is seen all along the capillary loops.

Image 2.7:

The immunofluorescence pattern is seen at higher power here. This is a granular pattern (not "linear" as in Goodpasture's syndrome).

Image 2.8:

A similar immunofluoresence pattern occurs with staining against complement C1q.

Image 2.9:

The thickened basement membrane from immune complex deposition in the glomerular capillary loop is prominent in this electron micrograph. In this EM photograph, the deposits are dark and located in a subendothelial position.

Image 2.10:

By electron microscopy microtubular aggregates are seen at high magnification are seen here in glomerular endothelial cells.

Questions:

1. What is the diagnosis?

This is systemic lupus erythematosus (SLE).

2. Why is a renal biopsy being done? What difference would the results of this biopsy make?

A renal biopsy should be performed in order to evaluate the patient's prognosis and to determine therapy. Many different types of renal findings can be present, depending upon the amount and location of immune deposits (this will be studied in more detail in the section on renal pathology next quarter). Each type of finding carries a different prognosis and would be treated in a slightly different manner. The presence of large amounts of subendothelial deposits in a diffuse proliferative distribution is the most serious type of pathologic finding and requires the most vigorous treatment.

3. What would a test for extractable nuclear antigens (ENA)--double stranded DNA--show? Should you also do an LE cell test?

ENA tests diagnostic for SLE include double stranded DNA and Smith antigen, but they do not have a high sensitivity. In general, presence of anti-dsDNA suggests a worse prognosis while presence of anti-Smith suggests a less aggressive course for SLE. An LE test, which is the earlier form of testing done to show antibodies directed against nuclear components, is no longer performed since ANA and ENA tests are more specific.

4. What other organ system involvement would you expect?

SLE can involve many organs, particularly skin (rash, photosensitivity), kidney (glomerulonephritis with renal failure), and joints (arthritis). Hematologic manifestations may include anemia, thrombocytopenia, and leukopenia. Diffuse central nervous system involvement can occur.

5. What immunologic mechanisms are operative in this disease?

The most common immunologic mechanism thought to play a role in SLE is type III hypersensitivity (immune complex mediated hypersensitivity). The cytopenias may be the result of type II (complement mediated) hypersensitivity.