Increased loss of the Y chromosome in peripheral blood cells in male patients with autoimmune thyroiditis

Persani, Luca; Bonomi, Marco; Lleo, Ana; Pasini, Simone; Civardi, Fabiola; Bianchi, Ilaria; Campi, Irene; Finelli, Palma; Miozzo, Monica; Castronovo, Chiara; Sirchia, Silvia Maria; Gershwin, M. Eric; Invernizzi, Pietro

doi:10.1016/j.jaut.2011.11.011

Cited by 68 publications

(49 citation statements)

References 43 publications

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“…Sex-related differentiation of the immune system is not only dependent on steroid influence (Pennel et al 2012), but also on the genes located on the X chromosome and its skewed inactivation (Quintero et al 2012). Recently, Y chromosome's protective function against autoimmune diseases also is being considered (Persani et al 2012). A goiter is not commonly seen in HT as confirmed in the present study.…”

Section: Discussionsupporting

confidence: 79%

Immunological Characteristics of Children with Hashimoto’s Autoimmune Thyroiditis

Kucharská

Górska

Stelmaszczyk-Emmel

et al. 2014

Advances in Experimental Medicine and Biology

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The main cause of autoimmune thyroiditis of Hashimoto's type (HT) is a pathological immune response to thyroid antigens. The aim of the study was to present clinical characteristics and immune profile of children with HT. Ninety five children were examined: 45 with HT (age: 8-18 years) and 50 healthy age-matched controls. The peripheral blood mononuclear cells' (PBMC) phenotype was evaluated using a Beckman Coulter flow cytometer with the following monoclonal antibodies: CD4-FITC, CD28-PC5, CD152-PE and CD8-FITC, CD28-PC5, CD152-PE. The thyroid stimulating hormone, thyroid hormones, and antibodies against thyroid peroxidase (TPO) and thyroglobulin (TG) were evaluated by a microparticle enzyme immunoassay. We found that goiter was present in 53% of children, the thyroid had an increased density in palpation in 98%, and hypothyroidism was diagnosed in 11% of HT patients. The number of CD152+ was lower in HT than in healthy children (p<0.05). CD4+ and CD8+ PBMC subsets did not differ between the groups at baseline. After stimulation with phytohemagglutinine (PHA), CD4+ cells decreased in healthy controls and remained constant in HT children. Anti-TPO and anti-TG antibodies were higher in children with a lower percentage of CD152+. No other markers correlated with the immunological profile of PBMC. The percentages of CD4+ and CD152+ negatively correlated with the anti-TG concentration. We conclude that children with HT have a different PBMC profile than healthy children and show a different pattern of response to stimulation.

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Section: Discussionsupporting

confidence: 79%

Immunological Characteristics of Children with Hashimoto’s Autoimmune Thyroiditis

Kucharská

Górska

Stelmaszczyk-Emmel

et al. 2014

Advances in Experimental Medicine and Biology

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“…Loss of the Y chromosome in blood cells has also been suggested to be involved in the pathogenesis of rare autoimmune conditions, such as autoimmune thyroiditis (Persani et al 2012) and primary biliary cirrhosis (Lleo et al 2013). For example, in an analysis of LOY in blood cells, using FISH in men diagnosed with autoimmune thyroiditis, it was found that 31 male patients had on average a higher level of mosaicism compared with 88 healthy controls (Persani et al 2012).…”

Section: Loy In Blood Cells and Risk For Diseasementioning

confidence: 99%

“…For example, in an analysis of LOY in blood cells, using FISH in men diagnosed with autoimmune thyroiditis, it was found that 31 male patients had on average a higher level of mosaicism compared with 88 healthy controls (Persani et al 2012). The level of LOY in blood was associated with age in both groups and the level of LOY mosaicism increased at a higher rate in the patient population compared to the healthy controls.…”

Section: Loy In Blood Cells and Risk For Diseasementioning

confidence: 99%

“…The studies discussed above describe associations between LOY in blood cells and increased risk for various diseases (Holmes et al 1985; Lippert et al 2010; Persani et al 2012; Lleo et al 2013; Chapiro et al 2014; Forsberg et al 2014; Ganster et al 2015; Dumanski et al 2016; Noveski et al 2016; Zhou et al 2016). A critical question to address is how could LOY affecting non-cancerous cells in the peripheral blood can be associated with disease processes in other organs, such as neoplastic proliferation of cells leading to tumors in other organs or neurodegenerative processes in the central nervous system?…”

Section: Loy In Blood Cells Associated With Disease Processes In Othementioning

confidence: 99%

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Loss of chromosome Y (LOY) in blood cells is associated with increased risk for disease and mortality in aging men

Forsberg

2017

Hum Genet

113

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Recent discoveries have shown that harboring cells without the Y chromosome in the peripheral blood is associated with increased risk for all-cause mortality and disease such as different forms of cancer, Alzheimer’s disease, as well as other conditions in aging men. In the entire world, the life expectancy of men is shorter compared to women, a sex difference that has been known for centuries, but the underlying mechanism(s) are not well understood. As a male-specific genetic risk factor, an increased risk for pathology and mortality associated with mosaic loss of chromosome Y (LOY) in blood cells could help to explain that men on average live shorter lives compared to women. This review primarily focuses on observed associations between LOY in blood and various diseases in aging men. Other topics covered are known risk factors for LOY, methods to detect LOY, and a discussion regarding mechanisms such as immunosurveillance, that could possibly explain how an acquired mutation in blood cells can be associated with disease processes in other organs.

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“…[35] uważają, że u chorych płci męskiej z AIChT może dochodzić do utraty rejonu pseudoautosomalnego chromosomu Y, co powoduje haploinsuficjencję genów z PAR1 i PAR2 w analogicznym mechanizmie, jak w przypadku monosomii chromosomu X u płci żeńskiej. W swoim badaniu stwierdzili, że u mężczyzn z AIChT czę-ściej niż w zdrowej grupie kontrolnej dochodzi do utraty chromosomu Y w limfocytach obwodowych [35]. Można więc przypuszczać, że wraz z utratą chromosomu Y są oni pozbawieni czynnika, który chroni płeć męską przed chorobami autoimmunizacyjnymi.…”

Section: Brak Dojrzałych Limfocytów B I Immunoglobulin Wszystkich Klasunclassified

Sex and autoimmune thyroid diseases

Kucharská¹

2014

Pediatr. Endocrinol.

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STRESZCZENIE/ABSTRACTAutoimmunizacyjne choroby tarczycy (AIChT) występują znacznie częściej u kobiet niż u mężczyzn, co sugeruje, że dla ich rozwoju istotne znaczenie mają czynniki związane z płcią. Ustalono, że istnieje wyraźny dymorfizm płciowy układu immunologicznego. U kobiet stwierdza się wyższą liczbę limfocytów CD4+, zwiększony stosunek subpopulacji CD4+ do CD8+ i preferencję odpowiedzi zależnej od Th2. U mężczyzn z kolei stwierdza się wyższą aktywność komórek NK oraz preferencję odpowiedzi zależnej od Th1. Podobne zjawiska zaobserwowano na zwierzęcych modelach doświadczalnych. Istnieje wiele hipotez, które mają wyjaśnić potencjalne przyczyny zwiększonej podatności płci żeńskiej na AIChT. Wśród nich za najistotniejsze uważa się czynniki genetyczne związane z chromosomami płciowymi. Na chromosomie X są zlokalizowane geny ważne dla regulacji odpowiedzi immunologicznej: m.in. Foxp3 (Xp11.23), CD40L (Xq26), BTK (Xq21.33-q22), IL2RG (Xq13.1), XIAP (Xq25). Sugeruje się także znaczenie ukierunkowanej inaktywacji drugiego chromosomu X, która występuje częściej u kobiet z autoimmunizacyjnymi chorobami tarczycy. Kolejnym możliwym czynnikiem jest zjawisko mikrochimeryzmu płodowego, który stwierdza się częściej u kobiet z AIChT. Znaczenie może mieć również zaburzenie funkcji microRNA (miRNA), które jest istotnym regulatorem odpowiedzi immunologicznej, a chromosom X zawiera aż 10% całego miRNA genomowego. Wydaje się także, że chromosom Y może pełnić rolę protekcyjną. Endokrynol. Ped. 13/2014;2(47):57-64.Autoimmune thyroid diseases (AITD) are much more frequent in female than male. This fact suggests a strong influence of sex dependent factors in AITD development. It was confirmed that immune system function is dimorphic in male and female. In females there is increased number of CD4+ T cells, increased proportion of CD4+ cells to CD8+cells and preferential Th2-dependent immune response. In males the activity of NK cells is increased and Th1-dependent immune response is preferential. Similar phenomena were observed in experimental animal models. Many theories arise to explain the reason of increased susceptibility to AITD in female. As the most important are considered genetic factors linked to sex chromosomes. On the X chromosome are located genes important for immune response regulation, i. e. Foxp3 (Xp11.23), CD40L (Xq26), BTK (Xq21.33-q22), IL2RG (Xq13.1), XIAP (Xq25). Additionally

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Increased loss of the Y chromosome in peripheral blood cells in male patients with autoimmune thyroiditis

Cited by 68 publications

References 43 publications

Immunological Characteristics of Children with Hashimoto’s Autoimmune Thyroiditis

Immunological Characteristics of Children with Hashimoto’s Autoimmune Thyroiditis

Loss of chromosome Y (LOY) in blood cells is associated with increased risk for disease and mortality in aging men

Sex and autoimmune thyroid diseases

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