Turner syndrome is caused by the presence of only one normally functioning X-chromosome. The other sex chromosome can be missing (45,X) or abnormal and mosaicism is often present. Occurring in one of every 2000 female births, Turner syndrome is one of our most common sex chromosome abnormalities 1. Turner syndrome is characterized by short stature, no spontaneous puberty and infertility due to ovarian dysgenesis 2. Besides the typical features of Turner syndrome ear problems are common. During childhood the girls repeatedly suffer from otitis media and a progressive sensorineural hearing disorder is commonly seen 3456.

Immunological disturbances have previously been described in Turner syndrome, with an association to reduced levels of serum IgG and IgM, increased IgA and decreased levels of circulating T- and B-lymphocytes. However the results have not been conclusive 6789.

Also different autoimmune diseases have been connected to Turner syndrome. An increased incidence of anti-thyroid antibodies has repeatedly been reported and thyroid dysfunctions are common 2101112. Other autoimmune diseases described are inflammatory bowel disease, insulin dependent diabetes mellitus (IDDM), Addison's disease, rheumatoid arthritis, myasthenia gravis, vitiligo, alopecia, pernicious anaemia and hypoparathyroidism, but the association to Turner syndrome is not definite 10.

Normally Addison's disease is often associated with other autoimmune diseases, such as thyroiditis, IDDM, premature ovarian failure (POF), vitiligo and hypoparathyroidism. Addison's disease may be present as an isolated disorder or part of type I or II autoimmune polyendocrine syndrome (APS I or APS II), where also pernicious anaemia, gastrointestinal dysfunctions, alopecia and chronic candidiasis are common 13. Several autoantigens have been identified to be connected to these three disorders as illustrated in table 1131415161718. Autoimmune inner ear disease is a multifactorial disorder that lately has been discussed. These patients often present autoantibodies or cellular factors, directed against several inner ear structures, but the etiology is still not completely characterized 192021. Of the autoantibodies seen in APS I, tyrosine hydroxylase (TH) could be a possible cochlear autoantigen, as it has been proposed as potential melanin catalyser in the inner ear 22. Some inner ear diseases are known to be caused by water and ion regulating problems, which is the case with Addison's disease.

The aim of this study was to investigate girls and women with Turner syndrome regarding autoantibodies connected to the autoimmune disorders APS 1, APS II and Addison's disease, to screen for overlapping profile of autoantibodies.

When screening for autoantibodies the only autoantibody overrepresented was that against TPO (40%), correlating to an increased incidence of thyroid dysfunctions among the Turner patients. This is in concordance with previously described prevalence of thyroiditis (20–50%). However in earlier studies even higher prevalence of anti-thyroid autoantibodies (50–85%) has been observed 10. This discrepancy could depend on differences in patient selection and/or methods. There is a known connection between hypothyroidism and hearing dysfunction 23. However, hearing loss was not over represented in the group with anti-TPO antibodies.

Considering that many of the autoimmune diseases documented in Turner syndrome 101112 also are seen in APS I and APS II, one could imagine an overlapping autoantibody profile. In this study the only autoantibodies found in Turner syndrome were directed against TH and TPH, in two respectively one woman with Turner syndrome. TH autoantibodies were also found in a few healthy blood donors. Antibodies to 21-OH, the most important autoantigen in Addison's disease 13, were not registered in any of the women with Turner syndrome, which is in line with that none of the examined patients presented any symptoms of Addison's disease. Only a few other autoimmune diseases were present in the group of Turner patient (see materials and methods), however these data were obtained through the medical history. Consequently a putative relation between Turner syndrome and the autoimmunity seen in APS I or APS II seems weak.

Turner females have a progressive hearing loss, both in the midfrequencies and also in the high frequencies 34, why an autoimmune situation could be suspected. In this study the only potential cochlear antigen investigated was TH. As TH autoantibodies were found only in two patients, not correlating to a hearing disability, TH does not appear to be an autoantigen connected to the sensorineural hearing loss seen in Turner syndrome. One hypothesis, put forward by Barrenäs et al., is that the ear and hearing problems are correlated to the degree of X chromosome loss, leading to growth disturbances during fetal life 24. An additional theory discussed is that the age dependent sensorineural hearing impairment may be enhanced because of the lack of estrogens 25.

In conclusion the autoimmune disorders sometimes associated with Turner syndrome do not seem to be of the same origin as Addison's disease, APS I or APS II.

The authors declare that they have no competing interests.

AES participated in the design of the study, analyzed the results and drafted the manuscript. LS participated in the design of the study and collected the blood samples. HH and OK performed the In vitro transcription and translation and immunoprecipitation and analyzed the results. MH participated in the design and coordination of the study and collected the blood samples.

All authors read and approved the final manuscript.