Graves' Disease in Pediatric and Elderly Patients with 22q11.2 Deletion Syndrome

Abstract

22q11.2 Deletion Syndrome (22qDS) is often complicated by autoimmune diseases. To clarify the causal relationship, we examined the lymphocyte subset distribution and the human leucocyte antigen (HLA) in two female patients (one child and an elderly) with Graves' disease (GD) and 22qDS. Thymus dysgenesis might have contributed to the T-cell imbalance and the lack of negative selection in both cases. Notably, HLA-DR14, a known risk factor for GD in Japanese individuals and the decreased regulatory T-cell numbers that were seen in the pediatric case, may affect the early onset of GD. Central and peripheral tolerance and Th1 cells appeared to be associated with the pathogenesis of GD in 22qDS.

Comprehensive research on thyroid diseases associated with autoimmunity: autoimmune thyroid diseases, thyroid diseases during immune-checkpoint inhibitors therapy, and immunoglobulin-G4-associated thyroid diseases

“…Treg dysfunction was suggested to be associated with GD [21]. We have reported pediatric and elderly GD patients with 22q11.2 deletion who exhibited dysfunction of central and peripheral tolerances [22].…”

Autoimmune Thyroid Disease in Specific Genetic Syndromes in Childhood and Adolescence

“…In this regard, abnormal thymic development may lead to decreased AIRE expression and consequently impaired AIRE-mediated intrathymic expression of tissue-restricted antigens (TRAs) ( 140 ). (2) Certain HLA haplotypes, such as HLA-DR14 may increase susceptibility to GD in patients with 22q11.2DS ( 139 , 141 ). (3) Thymic maldevelopment may result in several immunologic abnormalities.…”

“…T-cell lymphopenia and decreased absolute counts of CD4+CD25+ natural Tregs have been observed in 22q11.2DS patients especially during the first 4 years of life and might explain the early age of GD onset in some cases ( 142 – 144 ). (4) Furthermore, lymphopenia and restricted T cell repertoires, abnormal T cell activation and associated B cell dysregulation and humoral dysfunction, as well as Th1/Th2 imbalance of the CD4+ T cells may also be implicated in the induction of autoimmunity ( 130 , 141 , 145 , 146 ) ( Table 1 ).…”

Hashimoto’s Thyroiditis and Graves’ Disease in Genetic Syndromes in Pediatric Age

“…Several studies described an association between 22q11DS and GD [105,106,108,110]. If compared with the general pediatric population, GD in 22q11DS seems to be more frequent and may occur earlier, even under the age of 3 [107].…”

“…If compared with the general pediatric population, GD in 22q11DS seems to be more frequent and may occur earlier, even under the age of 3 [107]. According to some authors, certain HLA haplotypes (such as HLA-DR14) and the decreased Treg number may be involved in the early onset of GD in 22q11DS children [106].…”