Adult-Onset Immunodeficiency Syndrome

Since 2004, several infectious diseases caused by opportunistic pathogens have been detected in adults without immunodeficiency. They were not infected with HIV but, similar to AIDS, showed clinical manifestations due to extremely low immunity. Browne et al. first proposed the term "adult-onset immunodeficiency syndrome" to describe this new type of disease, as the main patient group consists of adults. To date, a few studies on AOID have been conducted and published. The cumulative reports confirmed the crucial role of anti-IFN-γ autoantibodies in the pathogenesis of AOID (Chen LF et al. 2021).

Adult immunodeficiency syndrome due to anti-interferon (IFN)-γ autoantibodies (AOID) is a rare, acquired immunodeficiency syndrome that usually occurs in previously healthy people and usually manifests as chronic, recurrent and difficult-to-control infections that can only be effectively treated with aggressive antibiotic therapy. The syndrome is also known as AIDS-like syndrome.

The anti-IFN-gamma autoantibody has been identified as an important risk factor (Nagamura N et al. 2021). Neutralizing anti-IFN-gamma autoantibodies are detectable in about 88% of AOIDs with multiple opportunistic infections (Browne SK et al. 2012). The causes for the development of anti-interferon-gamma autoantibodies are unknown. However, it is assumed that genetic factors play a significant role. The syndrome mainly affects Asians. Furthermore, the syndrome is highly associated with the expression of the human leukocyte antigen (HLA). There is an association of HLA-DQB1*05:01 and HLA-DQB1*05:02 (Chen LF et al. 2021).

Adults aged around 50 years (18-78 years).

In patients with AOID, the clinical presentation, the site of infection and the corresponding pathogens can be variable. Non-tuberculous mycobacteria (NTM) are the most common pathogenic microorganisms. Rapidly growing mycobacteria (RGM), such as Mycobacterium abscessus, are the most common NTM species isolated from patients in Thailand, China and the Philippines, while Mycobacterium avium complex (MAC) is mainly found in Japanese and non-Asian patients (Chen LF et al. 2021).

Recently, an increasing number of disseminated NTM infections have been observed in HIV-negative individuals without overt immunosuppression, and anti-IFN-γ autoantibody has been identified as an important risk factor (Nagamura N et al. 2021). Talaromyces marneffei (T. marneffei) is another extremely important pathogen of AOID. T. marneffei infection in humans is thought to be caused by inhalation of T. marneffei conidia in the environment. After entering the human body, it can multiply in the form of yeasts in macrophages and cause an infection ranging from a local infection in the lungs and skin to a disseminated systemic infection. In addition, other microorganisms such as Salmonella species, Cryptococcus neoformans, histoplasmosis capsules, Burkholderia pseudomallei, Listeria, varicella-zoster virus, cytomegalovirus and Epstein-Barr virus are also frequently identified as opportunistic pathogens in this patient group (Chen LF et al. 2021).

Co-infection with at least 2 pathogens is of great importance for the diagnosis of AOID.

Associations of AOID and neutrophilic dermatoses are known (Chen YC et al. 2022)

Adult onset immunodeficiency syndrome (AOID) is different from primary immunodeficiency disease (PID). Patients with AOID always have high titers of anti-IFN-gamma autoantibodies, which is strongly associated with higher mortality. With the outbreak of COVID-19), autoantibodies against type I IFNs (anti-IFN-I autoantibodies) have been found to be associated with the severity of COVID-19 (Bastard P et al. 2020).

Genetic deficiencies of the innate immune system lead to severe infections with intracellular pathogens, which is known as Mendelian susceptibility to mycobacterial diseases(MSMD).

Standardized antimicrobial therapy is the most important treatment, but it is still difficult to cure AOID patients with anti-IFN-γ autoantibodies by using antibiotics alone (Chen LF et al. 2021. Lowering the titer of anti-IFN-γ autoantibodies is considered the key to curing patients. Treatments such as plasmapheresis to break down the antibodies have also proven effective. Furthermore, measures to inhibit the production of reactive B cells and plasma load depletion have proven useful (de Prost N et al. 2021).

Since anti-type I IFN (IFN-I) autoantibodies also play an important role in the development of COVID-19, pre-existing anti-IFN-I autoantibodies are associated with an increased risk of severe COVID-19 disease. Put simply, anti-IFN autoantibodies with high titers in serum, regardless of the type of interferons, interrupt the activation of the downstream response pathway by blocking the connection between IFNs and their receptor, leading to an increased infection rate (Chen LF et al. 2021).

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