Adult‐onset immunodeficiency due to anti‐interferon‐gamma autoantibody‐associated Sweet syndrome: A distinctive entity

Abstract Background Severe and disseminated non-tuberculous mycobacterial (NTM) infections are frequently linked to a genetic predisposition but acquired defects of the interferon gamma (IFNγ) / interleukin 12 (IL-12) pathway need to be considered in adult patients with persistent or recurrent infections. Neutralizing anti-IFNγ autoantibodies disrupting IFNγ signalling have been identified as the cause of a severe and unique acquired immunodeficiency syndrome with increased susceptibility to NTM and other intracellular pathogens. Case presentation An adult Asian female with a previous history of recurrent NTM infections presented with persistent diarrhea, abdominal pain, night sweats and weight loss. Severe colitis due to a simultaneous infection with cytomegalovirus (CMV) and Salmonella typhimurium was diagnosed, with both pathogens also detectable in blood samples. Imaging studies further revealed thoracic as well as abdominal lymphadenopathy and a disseminated Mycobacterium intracellulare infection was diagnosed after a lymph node biopsy. Further diagnostics revealed the presence of high-titer neutralizing anti-IFNγ autoantibodies, allowing for the diagnosis of adult-onset immunodeficiency with anti-IFNγ autoantibodies (AIIA). Conclusions We here present a severe case of acquired immunodeficiency with anti-IFNγ autoantibodies with simultaneous, disseminated infections with both viral and microbial pathogens. The case illustrates how the diagnosis can cause considerable difficulties and is often delayed due to unusual presentations. Histological studies in our patient give further insight into the pathophysiological significance of impaired IFNγ signalling. B-cell-depleting therapy with rituximab offers a targeted treatment approach in AIIA.

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Skin Manifestations in Patients with Adult-onset Immunodeficiency due to Anti-interferon-gamma Autoantibody: A Relationship with Systemic Infections

Acta Dermato Venereologica ◽

10.2340/00015555-2959 ◽

2018 ◽

Vol 98 (8) ◽

pp. 742-747 ◽

Cited By ~ 5

Author(s):

K Jutivorakool ◽

P Sittiwattanawong ◽

K Kantikosum ◽

C Hurst ◽

C Kumtornrut ◽

...

Keyword(s):

Interferon Gamma ◽

Adult Onset ◽

Skin Manifestations ◽

Systemic Infections

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Subcutaneous Sweet syndrome associated with disseminated nontuberculous mycobacterial infection leading to the diagnosis of adult-onset immunodeficiency

Journal of the American Academy of Dermatology ◽

10.1016/j.jaad.2014.01.855 ◽

2014 ◽

Vol 71 (1) ◽

pp. e20-e22 ◽

Cited By ~ 4

Author(s):

Hsiao-Han Wang ◽

Yu-Chen Huang ◽

Wei-Yu Chen ◽

Ying-Yi Chiang

Keyword(s):

Mycobacterial Infection ◽

Adult Onset ◽

Sweet Syndrome ◽

Nontuberculous Mycobacterial Infection

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Non-tuberculous mycobacterial infection and reactive dermatosis associated with adult-onset immunodeficiency due to anti–interferon-gamma autoantibodies

Medicine ◽

10.1097/md.0000000000021738 ◽

2020 ◽

Vol 99 (36) ◽

pp. e21738

Author(s):

Xiao-Na Liang ◽

Yan-Fei Bin ◽

Guan-Ting Lai ◽

Ying-Hua Li ◽

Jian-Quan Zhang ◽

...

Keyword(s):

Interferon Gamma ◽

Mycobacterial Infection ◽

Adult Onset

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Latticed Gold Nanoparticle Conjugation via Monomeric Streptavidin in Lateral Flow Assay for Detection of Autoantibody to Interferon-Gamma

Diagnostics ◽

10.3390/diagnostics11060987 ◽

2021 ◽

Vol 11 (6) ◽

pp. 987

Author(s):

Weeraya Thongkum ◽

Umpa Yasamut ◽

Koollawat Chupradit ◽

Supachai Sakkhachornphop ◽

Jiraprapa Wipasa ◽

...

Keyword(s):

Sensitivity And Specificity ◽

Interferon Gamma ◽

Colloidal Gold ◽

Enzyme Linked Immunosorbent Assay ◽

Adult Onset ◽

Elisa Titer ◽

Mycobacterial Diseases ◽

Ifn Γ ◽

Immunodeficiency Syndrome ◽

Specific Symptoms

Adult-onset immunodeficiency syndrome (AOID) patients with autoantibodies (autoAbs) against interferon-gamma (IFN-γ) generally suffer from recurrent and recalcitrant disseminated non-tuberculous mycobacterial diseases. Since the early stages of AOID do not present specific symptoms, diagnosis and treatment of the condition are not practical. A simplified diagnostic method for differentiating AOID from other immunodeficiencies, such as HIV infection, was created. Anti-IFN-γ is generally identified using enzyme-linked immunosorbent assay (ELISA), which involves an instrument and a cumbersome process. Recombinant IFN-γ indirectly conjugated to colloidal gold was used in the modified immunochromatographic (IC) strips. The biotinylated-IFN-γ was incorporated with colloidal-gold-labeled 6HIS-maltose binding protein-monomeric streptavidin (6HISMBP-mSA) and absorbed at the conjugate pad. The efficacy of the IC strip upon applying an anti-IFN-γ autoAb cut-off ELISA titer of 2500, the sensitivity and specificity were 84% and 90.24%, respectively. When a cut-off ELISA titer of 500 was applied, the sensitivity and specificity were 73.52% and 100%, respectively.

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