Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA
Address for correspondence: Grant R. Yeaman, Ph.D., Department of Microbiology, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, NH 03756. Voice: 603-650-6329, ext. 6329; fax: 603-650-6223.
grant.yeaman{at}dartmouth.edu
Autoantibody responses to endometrial and serum antigens are
a common feature of endometriosis. We have shown that the serum
autoantibody response in endometriosis to a number of previously
identified antigens, including
2-Heremans Schmidt glycoprotein
and carbonic anhydrase, is specific for a carbohydrate epitope
common to these proteins. Removal of carbohydrate moieties from
these antigens resulted in a loss of antibody binding. Antibody
reactivity was abolished following adsorption with the lectin
jacalin, which specifically binds the Thomsen-Friedenreich (T)
antigen (Galß1-3GalNAc). Demonstration that the autoantibodies
also reacted with other Thomsen-Friedenreich antigen-bearing
proteins, such as serum IgA1, hemopexin, and MMP-9, confirmed
that this glycotope is involved in the autoantibody response.
However, the autoantibody binding requires the presence of at
least one sialic acid residue. Thus, the glycotope involved
may be a sialylated T antigen. These findings allow us to hypothesize
a number of mechanisms whereby the autoimmune response plays
a direct role in several aspects of the disease process. The
proposed mechanisms take into account the salient endocrine
dependency of endometriotic lesions and other aspects of the
disease process such as aberrant matrix metalloproteinase function
and the ability of endometrial cells to implant at ectopic sites.
The anti-T-like response may also be indicative of an underlying
genetic defect in glycosylation or in the control of glycosylation
by steroid sex hormones. Further characterization of this autoimmune
response may prove useful in the development of serum-based
diagnostic tests for endometriosis and may lead to the development
of therapeutic strategies.
