Purpose: Since we described for the first time a patient with IgG4 autoantibodies to IFN-γ more than 10 years ago, many patients with IFN-γ IgG4 autoantibodies have been described, mostly in Mongolian/ Asian patients with a particular HLA background and in association with disseminated nontuberculous mycobacterial infections. Very recently, the first Caucasian US patient was reported and we now present the case of a 65-year old Caucasian woman with severe disseminated Mycobacterium avium infection, cerebral toxoplasmosis and salmonella sepsis who was tested positive for IFN-γ deficiency due to unusual anti-IFN-γ IgG1 autoantibodies.
Methods: IFN-γ production after ex vivo ConA stimulation of the patient's whole blood and isolated peripheral blood mononuclear cells was assessed. Anti-human IFN-γ antibodies were measured by Ig/Ig-subclass-specific ELISA. In vitro physiologic relevance and blocking capacity of IFN-γ-stimulation by patient's serum was analysed by flow cytometric assessment of cytokine-induced phosphorylation of pSTAT1(Y701).
Results: Severely impaired IFN-γ production in the patient's whole blood but normal production in peripheral blood mononuclear cells in the absence of autologous serum was observed. High titre anti-IFN-γ antibodies of the IgG1 subclass could be demonstrated in the patient's serum by ELISA. Further, the addition of patient's serum to IFN-γ-stimulated immune cells showed inhibition of STAT1 phosphorylation.
Conclusions: IFN-γ autoantibodies of any IgG-isotype should be considered in patients with severe opportunistic infections independent of age at onset and ethnicity.