Immunological Profile and Predisposition to Autoimmunity in Girls With Turner Syndrome

Abstract

ObjectiveThe risk of autoimmune diseases (AD) in patients with Turner Syndrome (TS) is twice higher than in the general female population and four times higher than in the male population. The causes of the increased incidence of AD in TS are still under discussion. We hypothesized the presence of a specific humoral, cellular, and regulatory T cell (Treg) immunity profile which predisposes to AD, disorders of immunity, and disorders of immune regulation.MethodsThe study encompassed 37 girls with TS and with no signs of infection. The control group included 11 healthy girls with no hormonal disorders. A medical history focused on AD and immunity disorders was taken from all participants. The levels of: immunoglobulins IgG, IgA, IgM, total lymphocytes, lymphocytes subpopulations CD3+, CD4+, CD8+, CD19+, natural killer cells, Treg cells (CD4+ CD25+ CD127− FOXP3+), anti-inflammatory cytokines (interleukin-10, transforming growth factor-β), anti-nuclear antibodies, glutamic acid decarboxylase (GAD65 Abs), anti-thyroid peroxidase (anti-TPO Ab), and anti-thyroglobulin (anti-TG Ab) autoantibodies were determined in each participant.ResultsThe mean age and BMI in the TS group and in controls were comparable (11.9 ± 4.1 vs. 12.5 ± 4.0 years; 19.2 ± 3.4 vs. 19.7 ± 4.6, p > 0.05). Mean hSDS was significantly higher in controls (−2.2 ± 0.9 vs. −0.4 ± 1.5, p < 0.0001). AD and recurrent otitis media with complications were previously confirmed in 9 (24.3%) and 10 (27.0%) girls with TS. The TS group had significantly lower levels of IgG (p = 0.02), lower%CD4 (p < 0.001) and a significantly lower CD4:CD8 ratio than the controls (p < 0.001). There were no differences in mean Treg% between girls with TS and healthy controls. However, comparing Treg% between the TS group with coexisting autoimmunity and the remaining participants, a statistically significant difference was observed (2.09 ± 0.5 vs. 2.77 ± 1.6, p = 0.048). Patients with iXq had lower CD4% and more frequently had positive anti-TPO Ab and anti-TG Ab compared to the remaining girls with TS and controls (p = 0.001, p < 0.001, p = 0.01).ConclusionTS predisposes to AD, especially if associated with coexisting iXq. Our preliminary findings show that patients with TS may present a specific profile of humoral and cellular immunity markers, different from healthy girls.

Autoimmune Thyroid Disease in Specific Genetic Syndromes in Childhood and Adolescence

“…The impact of a specific karyotype on the prevalence of thyroid autoimmunity in TS women has been also addressed with conflicting results. Increased frequency of thyroid autoimmunity has been observed among TS patients with isochromosome Xq and isolated Xp deletion (33,(50)(51)(52). Common feature of the aforementioned chromosomal abnormalities is the lack of the short arm of the X chromosome (Xp), indicating that haploinsufficiency of immune-related genes located in the Xpter-p11.2 region may predispose to the development of thyroid autoimmunity in women with TS (51).…”

Recognition and management of adults with Turner syndrome: From the transition of adolescence through the senior years

“…FOXP3 is a transcription factor important in the development of regulatory CD4 T cells, and loss of this gene has been linked to the development of autoimmunity (Su et al, ). No differences in the percentage of regulatory T cells have been found between girls with Turner syndrome and controls, although girls with Turner syndrome who already had autoimmune disease had a significantly lower regulatory T cell percentage (Gawlik et al, ). PTPN22, ZFAT and MYO9B polymorphisms have been studied in pediatric and adult individuals with Turner syndrome in diverse populations (Bianco et al, ; Villanueva‐Ortega et al, ).…”

Turner syndrome with idiopathic thrombocytopenic purpura in childhood

“…TS predisposes to AD, especially if associated with coexisting isochromosome Xq (iXq). The most common AD associated with TS is Hashimoto's thyroiditis . The present patient was euthyroid, but positive for anti‐thyroglobulin antibody and anti‐thyroid peroxidase antibody.…”

“…The risk of autoimmune disease (AD) in patients with TS is approximately twice as high as that in the general female population . The mechanism responsible for complications involving AD and TS was unclear, but reportedly is due to dysfunction of regulatory T cells or IgG . TS predisposes to AD, especially if associated with coexisting isochromosome Xq (iXq).…”