Severe Disseminated <i>Mycobacterium avium</i> Infection in a Patient with a Positive Serum Autoantibody to Interferon-γ

Abstract

We herein report a case of disseminated Mycobacterium avium infection that involved both optic nerves, the conjunctiva, the right lower lung, and multiple skin lesions, including a thoracic nodule. The patient was a 65-year-old man without any significant medical history. The pathogen was detected in the patient's eye discharge, sputum, bronchial lavage fluid, and thoracic nodule. Anti-mycobacterial chemotherapy, including clarithromycin, rifampicin, and ethambutol, was administered, and the thoracic nodule was resected. An autoantibody to interferon-γ was detected in the patient's serum. Bilateral swelling of his optic nerves and facial dermatitis improved after initiating anti-mycobacterial chemotherapy.

Anticytokine autoantibodies leading to infection: early recognition, diagnosis and treatment options

“…Some interesting reports with more unusual presentations of nAIGA-related infection were recently published. Ikeda et al [12] reported a 65-year-old man from Japan with disseminated Mycobacterium avium infection involving both optic nerves in the context of wide dissemination. The neutralizing capacity of the AIGA was confirmed by STAT1 phosphorylation testing and as well reflected by an ‘invalid’ quantiferon assay showing no IFN-γ response to phytohemagglutinine [12].…”

“…Ikeda et al [12] reported a 65-year-old man from Japan with disseminated Mycobacterium avium infection involving both optic nerves in the context of wide dissemination. The neutralizing capacity of the AIGA was confirmed by STAT1 phosphorylation testing and as well reflected by an ‘invalid’ quantiferon assay showing no IFN-γ response to phytohemagglutinine [12]. Koizumi et al [13] presented a case of a 66-year-old Japanese HIV negative man with M. avium peritonitis and chylous ascites and nAIGA.…”

“…The most used functional tests for ascertainment of neutralizing activities of ACAA include cellular cytokine release tests and STAT phosphorylation assays (e.g. [12,27 ▪ ,49 ▪ ]).…”

“…Several recent reports noted indeterminate or invalid results when using standard clinical IFN-γ release testing such as Quantiferon or Elispot assays showing negative mitogen responses in patients with high titre AIGA in the context of disseminated NTM infection, probably mostly reflecting interference as the patients AIGA would mask any induced IFN-γ (e.g. [8 ▪▪ ,12]). Recent studies evaluated and showed an excellent usefulness of the mitogen component of the whole blood Quantiferon in-tube assays for the detection of clinical relevant AIGA [53 ▪ ,54 ▪ ].…”

Minireview: Insights into anti-interferon-γ autoantibodies

“…The most common assay used to detect anti-IFN-c AAbs is the enzyme-linked immunosorbent assay (ELISA), in indirect, 2,12,17,18,21,23,[36][37][38][39][40][41] sandwich, 14,16,32,42 or inhibitory 2,3,8,17,23,32,37,43,44 assay format. For the ELISAbased method, the results could be reported qualitatively (positive or negative) or quantitatively as optical density (OD), 39 titer, 43 or through calculations of arbitrary units 21 or ELISA units (EU). 36,39 The easy-to-use, low-cost Dot ELISA strip, which can be read directly on the strip, was developed as a point-of-care screening tool in remote settings.…”