Mycobacterium avium Complex Infections: Detailed Phenotypic and Functional Immunological Work-Up Is Required despite Genetic Analyses

Bernhard Kratzer, Katharina Grabmeier-Pfistershammer, Doris Trapin, Ulrike Körmöczi, Arno Rottal, Melanie Feichter, Petra Waidhofer-Söllner, Mateja Smogavec, Franco Laccone, Michael Hauser, Stefan Winkler, Winfried F Pickl, Arno M Lechner

Research output: Journal article (peer-reviewed)Journal article


INTRODUCTION: Cervical scrofulous lymphadenitis due to Mycobacterium avium complex (MAC) in immunocompetent adults is a rare disease. The presence of MAC infections demands meticulous clinical evaluation of patients along with detailed phenotypic and functional evaluation of their immune system including next-generation sequencing (NGS) analyses of target genes.

METHODS: Exact clinical histories of the index patients both suffering from retromandibular/cervical scrofulous lymphadenitis were obtained along with phenotypic and functional immunological evaluations of leukocyte populations followed by targeted NGS-based sequencing of candidate genes.

RESULTS: Immunological investigations showed normal serum immunoglobulin and complement levels, but lymphopenia, which was caused by significantly reduced CD3+CD4+CD45RO+ memory T-cell and CD19+ B-cell numbers. Despite normal T-cell proliferation to a number of accessory cell-dependent and -independent stimuli, the PBMC of both patients elaborated clearly reduced levels of a number of cytokines, including IFN-γ, IL-10, IL-12p70, IL-1α, IL-1β, and TNF-α upon TCR-dependent T-cell stimulation with CD3-coated beads but also superantigens. The IFN-γ production deficiency was confirmed for CD3+CD4+ helper and CD4+CD8+ cytotoxic T cells on the single-cell level by multiparametric flow cytometry irrespective of whether PMA/ionomycin-stimulated whole blood cells or gradient-purified PBMC was analyzed. In the female patient L1, targeted NGS-based sequencing revealed a homozygous c.110T>C mutation in the interferon-γ receptor type 1 (IFNGR1) leading to significantly reduced receptor expression on both CD14+ monocytes and CD3+ T cells. Patient S2 presented with normal IFNGR1 expression on CD14+ monocytes but significantly reduced IFNGR1 expression on CD3+ T cells, despite the absence of detectable homozygous mutations in the IFNGR1 itself or disease-related target genes. Exogenous addition of increasing doses of IFN-γ resulted in proper upregulation of high-affinity FcγRI (CD64) on monocytes from patient S2, whereas monocytes from patient L1 showed only partial induction of CD64 expression after incubation with high doses of IFN-γ.

CONCLUSION: A detailed phenotypic and functional immunological examination is urgently required to determine the cause of a clinically relevant immunodeficiency, despite detailed genetic analyses.

Original languageEnglish
Pages (from-to)914-931
Number of pages18
JournalInternational Archives of Allergy and Immunology
Issue number9
Early online date06 Jun 2023
Publication statusPublished - 01 Sept 2023


  • Cytokine production
  • Functional T cell analysis
  • Immunodeficiency
  • Interferon gamma receptor
  • Mycobacterium avium complex infections

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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