Combined Immunodeficiencies with Nonfunctional T Lymphocytes

Granulomatous inflammation: The overlap of immune deficiency and inflammation

“…Genes playing an important role in T-cell function can be affected but hypomorphic (partial loss-offunction) mutations in genes playing a key role in T-cell development (typically causing severe combined immune deficiency (SCID)) have also been described. In addition to increased susceptibility to infections, these patients can present a broad range of symptoms such as autoimmunity, granulomatous inflammation, lymphoproliferation, and increased risk of malignancy [66,67]. Granulomatous inflammation has been reported in patients with various genetic defects (Table 5), mainly hypomorphic recombination-activating gene (RAG) mutations [68], hypomorphic Artemis deficiency [69], hypomorphic JAK3 deficiency [70], CD40L deficiency [71], ataxia telangiectasia [72], Nijmegen breakage syndrome [73], cartilage hair hypoplasia [74], and lipopolysaccharideresponsive beige-like anchor (LRBA) deficiency [75].…”

The AMPK enzyme-complex: from the regulation of cellular energy homeostasis to a possible new molecular target in the management of chronic inflammatory disorders

“…Alterations and defects in the activity of these cells unavoidably lead to conditions of immunodeficiency or autoimmunity disorders [53]. The AMPK enzymatic complex is widely expressed in murine and human lymphocytes, where it is quickly activated following the interaction between T cells and antigens, thus suggesting a critical involvement of this enzyme in the regulation of lymphocyte activation and functions [54][55][56].…”

Omenn syndrome associated with a functional reversion due to a somatic second-site mutation in CARD11 deficiency

“…13 These conditions include diseases caused by mutations in ORAI1, [14][15][16] IKBKB, 17 or CARD11. 18,19 OS has not yet been reported in these disorders, supporting the concept that impaired T-cell development and a priori peripheral T-cell lymphopenia are essential parts of the pathogenesis of the characteristic features of OS.…”