Thymectomy in early childhood: Significant alterations of the CD4+CD45RA+CD62L+ T cell compartment in later life

Prelog, Martina; Keller, Michael; Geiger, Ralf; Brandstätter, Anita; Würzner, Reinhard; Schweigmann, Ulrich; Zlamy, Manuela; Zimmerhackl, Lothar Bernd; Grubeck‐Loebenstein, Beatrix

doi:10.1016/j.clim.2008.08.023

Cited by 95 publications

(96 citation statements)

References 43 publications

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“…Only two patients aged 5 and 8 years, had high titers (2560 and 512) of ANA, and none had anti-DNA. This is in contrast to absence of ANA or RF after thymectomy during cardiac operations in non-syndromic infants (34). Most of the patients had ANA and ASM in very low titers.…”

Section: Discussionmentioning

confidence: 66%

Hypoparathyroidism and autoimmunity in the 22q11.2 deletion syndrome

Lima

Abrahamsen

Wolff

et al. 2011

European Journal of Endocrinology

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Objective: To characterize the endocrine and autoimmune disturbances with emphasis on parathyroid dysfunction in patients with 22q11.2 deletion syndrome (22q11.2 DS). Design: In this nationwide survey; 59 patients (age 1-54 years) out of 86 invited with a 22q11.2 DS were recruited through all the genetic institutes in Norway. Methods: Data was collected from blood tests, medical records, a physical examination and a semistructured interview. We registered autoimmune diseases and measured autoantibodies, hormone levels and HLA types. Results: Twenty-eight (47%) patients had hypoparathyroidism or a history of neonatal or transient hypocalcemia. Fifteen patients had neonatal hypocalcemia. Fourteen patients had permanent hypoparathyroidism including seven (54%) of those above age 15 years. A history of neonatal hypocalcemia did not predict later occurring hypoparathyroidism. Parathyroid hormone levels were generally low indicating a low reserve capacity. Twenty-eight patients were positive for autoantibodies. Six (10%) persons had developed an autoimmune disease, and all were females (P!0.02). Hypoparathyroidism correlated with autoimmune diseases (P!0.05), however, no antibodies were detected against the parathyroid glands. Conclusions: Hypoparathyroidism and autoimmunity occur frequently in the 22q11.2 DS. Neonatal hypocalcemia is not associated with later development of permanent hypoparathyroidism. Hypoparathyroidism may present at any age, also in adults, and warrants regular measurement of calcium levels. Hypoparathyroidism and autoimmunity occur frequently together. Our findings of autoimmune diseases in 10% of the patients highlight the importance of stringent screening and follow-up routines.

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Section: Discussionmentioning

confidence: 66%

Hypoparathyroidism and autoimmunity in the 22q11.2 deletion syndrome

Lima

Abrahamsen

Wolff

et al. 2011

European Journal of Endocrinology

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“…The increase in proliferation rates were strongly related to the naive T cell pool contraction in the CD8 subset. Moreover, Prelog et al (2009) recently reported that young adults thymectomized in their childhood (an informative group of premature immunosenescence) showed higher rates of naive CD4 T cell proliferation that, eventually, leads to diminished sjTREC numbers at the CD4 naive T cell pool. This study indirectly showed, for the first time in humans, the potential relationship between the loss of thymic function and increased naive turnover rates at the CD4 T cell subset.…”

Section: Discussionmentioning

confidence: 99%

“…In humans, CD4-increased naive T cells proliferation has been reported in people over 65 and thymectomized children (Naylor et al 2005;Prelog et al 2009). The partial lymphopenia due to the loss of thymic function is believed to increase these proliferation rates (Kohler and Thiel, 2008;Nickolich-Zugich 2008).…”

Section: Introductionmentioning

confidence: 99%

Age-related deregulation of naive T cell homeostasis in elderly humans

Ferrando‐Martínez

Ruiz‐Mateos

Hernández

et al. 2010

AGE

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Immunosenescence is characterized by phenotypic and functional changes of effector memory T cells. In spite of the well-described senescent defects of these experienced T cells, immune responses to new pathogens are also deeply affected in elderly humans, suggesting that naive T cells could also show age-related defects. It has been reported in both, animal models and humans, alterations of the naive T cell turnover associated to advanced age or low thymic function. However, as far as we know, homeostatic mechanisms involved in the deregulation of naive T cell peripheral dynamics and their consequences are still not well understood. Thus, the aim of our study was to analyze homeostatic parameters of peripheral naive T cells and their relationship with thymic function in young and elderly humans. Our results show that lower naive T cell numbers were associated with a lower thymic function and higher activation and proliferating naive T cell levels. We then analyzed sjTREC numbers and relative telomere length from sorted naive T cells. Our results show that the aberrant activation and proliferation status was related to lower sjTREC numbers (a peripheral proliferation marker) and both, higher CD57 expression levels and shortened telomeres (replicative senescence-related markers). Elderly individuals show a greater contraction of the CD8 naive T cell numbers and all homeostatic alterations were more severe in this compartment. In addition, we found that low functional thymus show a CD4-biased thymocyte production. Taken together, our results suggest a homeostatic deregulation, affecting mostly the naive CD8 T cell subset, leading to the accumulation of age-associated defects in, otherwise, phenotypically naive T cells.

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“…In this study, thymectomyzed subjects also present higher numbers of neutrophils and low platelet counts but normal B lymphocyte and natural killer (NK) cell numbers. Low naive T cell counts, high proliferation rates among the naive subset and increased IL-7 bioavailability have been also observed (Prelog et al, 2009). This later result is especially interesting, since this naive T lymphocytes alteration is also a hallmark feature of immune senescence on healthy aging .…”

Section: Neonatal Thymectomy During Congenital Heart Disease Correctionmentioning

confidence: 72%