Journal of Autoimmunity (2001) 16, 151–161doi:10.1006/jaut.2000.0465, available online at http://www.idealibrary.com on
Autoantibodies in Endometriosis Sera Recognize a
Thomsen–Friedenreich-like Carbohydrate Antigen
Gillian A. Lang and Grant R. Yeaman
Department of Microbiology, Dartmouth
Medical School, Lebanon, NH, USA
Received 18 August 2000
Accepted 2 November 2000
Key words: autoantibodies,
carbohydrates,
endometriosis, sialic acid,
Thomsen–Friedenreich antigen
Autoantibody responses to endometrial antigens are a common feature of
endometriosis. Antibody responses to a number of serum and tissue antigens
such as
2
-Heremans Schmidt glycoprotein (
2
-HSG), transferrin, and carbonic
anhydrase have been identified. The nature of the epitopes recognized on
these proteins has not been determined. In this study we show that the serum
antibody response to
2
-HSG and carbonic anhydrase is against a common
carbohydrate epitope which is also expressed on bovine fetuin. Removal of
carbohydrate moieties from these antigens resulted in loss of antibody
binding. Antibody reactivity with
2
-HSG, fetuin and other antigens was
removed by binding with the lectin jacalin. Jacalin specifically binds the
Thomsen–Friedenreich antigen (Gal1-3GalNAc). Demonstrating that the
autoantibodies also reacted with other Thomsen–Friedenreich antigen-bearing
proteins, serum IgA1 and haemopexin confirmed an association with this
epitope. These antigens have not been previously described as autoantigens in
endometriosis and are of interest since they raise the possibility that this
autoimmune response may either play a direct role in the disease process
or reflect an abnormality of glycosylation in endometriosis. These results
may also prove useful in the development of a serum diagnostic test for
endometriosis.
© 2001 Academic Press
Introduction
Endometriosis is a disorder characterized by the
growth of endometrial cells at extrauterine (ectopic)
sites. It is a common disease which may affect up to
10% of women of reproductive age [1]. Although the
aetiology of endometriosis remains enigmatic, altered
cellular and humoral immune function is clearly a
feature of established disease [2–4]. Autoantibodies to
endometrial antigens have been described in a
number of studies (reviewed in [2]). Perhaps the best
characterized tissue antigens described thus far are
the human chorionic gonadotopin receptor [5] and
carbonic anhydrase isoforms I and II [6–8]. Antibodies
to transferrin and
2
-HSG have also been described
and proposed as diagnostic markers [9, 10]. Whilst
considerable work has been carried out in terms of
measuring the incidence of these autoantibodies in
endometriosis, reproductive diseases, and other
autoimmune diseases, the nature of the epitopes
involved has received little attention. All of the
autoantigens identified above are glycoproteins.
Carbohydrate antigens of these proteins have not been
evaluated in studies with only one apparent exception
[5]. The aim of the current study was to evaluate a
potential role for carbohydrate epitopes in the auto-
antibody response to the previously identified
endometriosis-associated autoantigens. We isolated
novel antigens from eutopic and ectopic endometria
from endometriosis patients. The results show that
carbohydrate moieties on these antigens are recog-
nized by autoantibodies in endometriosis. In addition,
we identified the serum glycoproteins IgA1 and hae-
mopexin as autoantigens in endometriosis. Reactivity
with these glycoproteins involves an antibody
response to an epitope related to the Thomsen–
Friedenreich antigen (TF) which is recognized by the
jackfruit lectin, jacalin.
Materials and Methods
Fresh serum, ectopic and eutopic endometrium were
obtained from hysterectomy patients with the
informed consent of the patients and Institution
Review Board approval. The stage of the menstrual
cycle of the endometrium was determined in
accordance with accepted histological practice
using hematoxylin/eosin-stained paraffin sections.
Evaluations were conducted independently by two
pathologists by scoring the degree of stromal edema
Correspondence to: Grant R. Yeaman, Ph.D., Department of
Microbiology, Dartmouth Medical School, 1 Medical Center Drive,
Lebanon, NH 03756, USA. Fax: 603-650-6223. E-mail:
Grant.R.Yeaman@Dartmouth.edu
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0896–8411/01/020151+11 $35.00/0 © 2001 Academic Press