Clinical Features of Candidiasis in Patients With Inherited Interleukin 12 Receptor β1 Deficiency

Abstract

Patients who are deficient in IL-12Rβ1 may have candidiasis, usually mucocutaneous, which is frequently recurrent or persistent. Candidiasis may be the first clinical manifestation in these patients.

Clinical and genetic features of IL12Rb1 deficiency: Single center experience of 18 patients

“…These patients are also susceptible to salmonella, candida and M. tuberculosis species 2,13,14 . Some other intracellular microorganisms have been reported in a small number of patients 13 .…”

The Evolving View of IL-17-Mediated Immunity in Defense Against Mucocutaneous Candidiasis in Humans

“…Experiments in nature suggest that patients with germ line mutations in STAT3 resulting in the complex clinical phenotype of hyper-IgE syndrome (HIES), AIRE mutation causing APS-1 and IL12Rβ1 deficiency causing increased susceptibility to atypical Mycobacteria and Salmonella are also susceptible to CMC [9][10][11][12][13]. Patients with these PIDs present with an impaired differentiation of IL17+CD4+ T cells (HIES and IL12Rβ1 deficiency) or increased production of anti-IL-17 antibodies (APS-1).…”

“…Unsurprisingly, the functional impairment of IL-12Rβ1 was found to result in a wide range of infections caused predominantly by intracellular pathogens [93][94][95][96][97][98]. T cells and NK cells from patients with IL-12Rβ1 mutation cannot respond to IL-12 or IL-23 because these cytokines bind to IL-12Rβ1 and these patients frequently develop CMC [11]. T cells and NK cells from patients with deficiency of the IL-12p40 subunit shared by IL-12 and IL-23 may also be susceptible to CMC because of the impaired maintenance of IL17+ T cells at mucosal surfaces.…”

“…Analyses of 156 patients with IL-12Rβ1 deficiency showed that 35 (23%) of such patients presented with clinical features of candidiasis [11]. Most patients were identified with recurrent and persistent CMC and candidiasis was the first documented clinical manifestation in 19 of 35 patients despite vaccination of 10 of these 19 patients with live bacille Calmette-Guérin vaccine.…”

“…Several primary immunodeficiency disorders (PIDs) typically characterized by CMC and impaired IL-17-mediated immunity have been identified recently [9]. CMC in such patients may be part of a complex clinical phenotype exemplified by dominant negative signal transducer and activator of transcription (STAT)3 deficiency, interleukin (IL)-12Rβ1 and IL-12p40 deficiencies, and autoimmune polyendocrine syndrome (APS) type 1 [10][11][12][13]. In a subgroup of PIDs, predisposition to superficial candidiasis may be the only or the dominant characteristic of the underlying genetic disorder (CMC disease, CMCD) [9].…”