Mycobacterium genavense is an opportunistic nontuberculous mycobacterium with a tropism for the intestinal tract first described in 1992 [3]. Initially known for life-threatening infections in people living with HIV, associations with other immune deficiencies have been described in recent years [4]. Cases in immunocompetent hosts are extremely rare. A recent meta-analysis has included only two cases of immunocompetent adults which may be attributed to mislabeling resulting from a failure to diagnose rare underlying immunodeficient conditions [4].

One important immune defense mechanism for the elimination of intracellular pathogens is signal amplification by the IL-12/IFN-γ circuit. Therefore, deficits in this pathway, such as the acquired adult-onset immunodeficiency nAIGA, predispose individuals to mycobacterial infections, but also other intracellular pathogens such as Salmonella or Toxoplasma. Possibly, the previous pleural empyema may have already occurred within the context of nAIGA [5]. Additionally, such conditions can also contribute to the pathogenesis of autoimmune diseases and tumors [6], suggesting a potential link to the patient’s diagnosis of Graves’ disease. His Philippine origin led us on the right track, as nAIGA predominantly affects individuals of Southeast Asian descent and appears to be associated with HLA alleles DRB*16:02 and DRB*05:02 [7, 8], that are expressed to a higher extend in the Asian population. Since we only tested T-SPOT.TB® ELISpot with an unsuspicious negative result we did not detect the hint to anti-IFN-γ autoantibodies earlier. A parallel use of QuantiFERON-TB Gold Plus® assay with no measurable IFN-γ production even not in the PHA-stimulated positive control of this QuantiFERON-TB Gold Plus® assay could have been suspicious for anti-IFN-γ autoantibodies before. Furthermore, it is worth mentioning that using a Quantiferon® assay could lead to an earlier discovery of the autoantibodies as through their presence no signal would be registered even in the positive control.

The treatment of infections with M. genavense generally consists of a combined antimycobacterial therapy for several months. The most common regimen includes a macrolide (e.g. clarithromycin, azithromycin), a rifamycin (e.g. rifabutin), and ethambutol [4]. In cases of an underlying IFN-γ deficiency and an inadequate response to antimycobacterial therapy, an additional immunostimulatory treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF), plasmapheresis, cyclophosphamide, or Rituximab has to be considered. When IFN-γ antibodies are absent at all a treatment with IFN-γ should be considered as well [9, 10]. However, this was not necessary in our case.

This case illustrates how a rare mycobacterial infection can lead to the diagnosis of an acquired adult-onset immunodeficiency that can also provide an explanation for other health conditions. It further emphasizes the necessity of always considering patients’ origins, as this can provide crucial clues.