The immunohistochemical localization of
2-HeremansSchmid glycoprotein/fetuin-A (AHSG)
Sir,
As reviewed by Floege and Ketteler [1], vascular calcification is a frequent complication found in patients with end-stage renal diseases (ESRD). It has been recognized that the serum levels of
2-HeremansSchmid glycoprotein/fetuin-A (AHSG) [2] are generally low in ESRD patients [3]. Recently, AHSG was shown to exert a calcification inhibitory action both in vitro and in vivo [4,5]. Thus, low levels of circulating AHSG may be one of the causes of ectopic calcification associated with uraemia [1]. In principle, we agree with this hypothesis; however, circulating molecules may not be the only AHSG that inhibits ectopic calcification.
We examined the localization of AHSG around lesions with ectopic calcification in dialysis patients. Anti-human AHSG antibody (DakoCytomation, Glostrup, Denmark) was used for the immunohistochemical study. Figure 1 shows ectopic calcification around the right wrist joint in a dialysis patient. Calcified tissue is indicated by von Kossa staining (Figure 1A). Note that AHSG-positive immunoreactivity surrounds the calcified tissue (Figure 1B).

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Fig. 1. A 62-year-old female who had been undergoing haemodialysis therapy for 15 years. Ectopic calcified tissue was extracted from the right wrist joint during surgical therapy for carpal tunnel syndrome. (A) Calcified tissue is indicated by the von Kossa staining (arrows). (B) The immunoreaction for AHSG can be seen surrounding the calcified tissue.
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AHSG seems to be assimilated into the tissues through passive or active mechanisms. On the other hand, the calcified lesions containing AHSG may not progress rapidly, since AHSG inhibits further calcification.
Thus, AHSG was found to be concentrated around ectopic calcified lesions. This type of localized deposition might enhance the calcification inhibitory action of AHSG in vivo.
Conflict of interest statement. None declared.
Junichiro J. Kazama1,
Fumitake Gejyo1 and
Isei Ei2
1 Niigata University Graduate
School of Medical and
Dental Sciences
Clinical Nephrology and Rheumatology2
Santo-Daini Hospital
Niigata
Japan
Email: jjkaz{at}med.niigata-u.ac.jp
References
- Floege J, Ketteler M. Vascular calcification in patients with end-stage renal diseases. Nephrol Dial Transplant 2004; 19 [Suppl 5]: 5962
- Gejyo F, Schmid K. Purification and characterization of the two forms of human plasma alfa 2HS-glycoprotein. Biochim Biophys Acta 1981; 671: 7884[ISI][Medline]
- Kishore BK, Gejyo F, Arakawa M. Alpha HS-glycoprotein in the serum and urine of patients with renal disease. Postgraduate Med J 1983; 59: 2831[Abstract]
- Scinke T, Amendt C, Trindl A, Poschke O, Muller-Esterl W, Jahnen-Dechent W. The serum protein alpha 2-HS glycoprotein/fetuin inhibits apatite formation in vitro and in mineralizing calvaria cells. A possible role in mineralization and calcium homeostasis. J Biol Chem 1996; 271: 2078920796[Abstract/Free Full Text]
- Schafer C, Heiss A, Schwarz A et al. The serum protein alpha 2-HeremansSchmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest 2003; 112: 357366[Abstract/Free Full Text]