Anti-cytokine autoantibodies could cause immunodeficiency and have been recently recognized as autoimmune phenocopies of main immunodeficiencies and are found in particular, but not exclusively in adult individuals. Syringin primary immunodeficiencies (Tangye et al. 2020), and are found in particular, but not exclusively in adult patients. Autoantibodies, produced by auto-reactive B cells, may bind to cytokines. In sufficient concentration, anti-cytokine autoantibodies could block the signaling and neutralize the biological function of target cytokines, by preventing the direct binding to its receptor and (or) depleting the cytokine through forming a cytokine/autoantibodies complex (Piccoli et al. 2015). Autoantibodies against cytokines are, however, not necessarily Syringin associated with a respective neutralizing activity (Karner et al. 2016; von Stemann et al. 2017). By blocking the cytokines biological function, patients with anti-cytokine autoantibodies may present with a similar clinical phenotype as the related inborn genetic disorders. Although the exact mechanism is largely unknown, the production of autoantibodies may require external exposure to cross-reactive antigens and multiple steps to break tolerance in the adaptive immune response. This may explain why most (but not all) patients with anti-cytokine autoantibodies present later in life. So Syringin far, autoantibodies to interferon (IFN)-, GM-CSF, to a group of TH-17 cytokines comprising IL-17A, IL-17F, IL-22, IL-23, and to IL-6 have been found to be causative or closely associated with susceptibility to infection. In contrast, high levels of neutralizing autoantibodies may not cause any expected effects in vivo, as, e.g., shown by patients with autoantibodies to type I IFNs (IFN and IFN), which do not present with increased susceptibility to viral infections (Weiler et al. 2018). It has been suggested that this may be because of a large number of redundant type I IFN species, resulting in incomplete neutralization of the overall antiviral activity of IFNs by the autoantibodies (Puel et al. 2010). Anti-interferon- autoantibodies as an etiology in mycobacterial infections in adults Interferon- is a key cytokine produced by activated T NF2 cells, natural killer cells, and group I innate lymphoid cells. IFN- receptors are expressed widely on most cell types, but especially on myeloid cell (such as macrophages and dendritic cells). The identification of IFN- receptor deficiencies (and (NTS), candidiasis and symptoms of tuberculosis (see Table ?Table1)1) (Bustamante et al. 2014). Table 1 . infection Nocardiae unknownApplen Clancey et al. (2019) CrumCianfione et al. (2017) Kuo et al. (2017) Punatar et al. (2012) Rosen et al. (2013) Rosen et al. (2015) Saijo et al. (2014) gain-of-function, loss-of-function, chronic mucocutaneous candidiasis High titers of highly neutralizing anti-IFN- autoantibodies (nAIGAs) were initially reported by several groups in sporadic patients or small case series with NTM infections (Doffinger et al. 2004; Hoflich et al. 2004; Kampmann et al. 2005; Patel et al. 2005). In recent years, however, larger cohorts of nAIGA patients were reported from Southeast Asia, with the majority from Thailand, Hong Kong, Taiwan and Japan (Aoki et al. 2018; Browne et al. 2012; Chi et al. 2013, 2016). Only few of the reported cases did not originate from this region (Hanitsch et al. 2015; Kampmann et al. 2005; O’Connell et al. 2014; van de Vosse et al. 2017). Around 500 patients with nAIGAs have been reported up to now in the literature but the exact prevalence rate of nAIGAs-related disease can be unfamiliar (Aoki et al. 2018; Barcenas-Morales et al. 2016, 2019; Browne 2014; Browne et al. 2012; Chi et al. 2013, 2016; Chruewkamlow et al. 2016; Doffinger et al. 2004; Hoflich et al. 2004; Jutivorakool et al. 2018; Kampmann et al. 2005; Patel et al. 2005; Wipasa et al. 2018; Wongkulab et al. 2013; Wu et al. 2018). Just like individuals with MSMD, mycobacterial attacks are the primary medical presentations for individuals with nAIGAs, and a significant proportion of the attacks (95%) is serious and disseminated (Aoki et al. 2018; Browne et al. 2012; Chi et al. 2016). Both, rapidly-growing and slowly-growing NTMs, are isolated from individuals with nAIGAs,.