Familial Aggregation of High Tumor Necrosis Factor Alpha Levels in Systemic Lupus Erythematosus

الملخص EN

Systemic lupus erythematosus (SLE) patients frequently have high circulating tumor necrosis factor alpha (TNF-α) levels.

We explored circulating TNF-α levels in SLE families to determine whether high levels of TNF-α were clustered in a heritable pattern.

We measured TNF-α in 242 SLE patients, 361 unaffected family members, 23 unaffected spouses of SLE patients, and 62 unrelated healthy controls.

Familial correlations and relative recurrence risk rates for the high TNF-α trait were assessed.

SLE-affected individuals had the highest TNF-α levels, and TNF-α was significantly higher in unaffected first degree relatives than healthy unrelated subjects (P=0.0025).

No Mendelian patterns were observed, but 28.4% of unaffected first degree relatives of SLE patients had high TNF-α levels, resulting in a first degree relative recurrence risk of 4.48 (P=2.9×10-5).

Interestingly, the median TNF-α value in spouses was similar to that of the first degree relatives.

Concordance of the TNF-α trait (high versus low) in SLE patients and their spouses was strikingly high at 78.2%.

These data support a role for TNF-α in SLE pathogenesis, and TNF-α levels may relate with heritable factors.

The high degree of concordance in SLE patients and their spouses suggests that environmental factors may also play a role in the observed familial aggregation.