{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T08:55:03Z","timestamp":1765961703375,"version":"3.40.5"},"reference-count":58,"publisher":"S. Karger AG","issue":"9","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int Arch Allergy Immunol"],"published-print":{"date-parts":[[2023]]},"abstract":"<jats:p>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-\u03b3, IL-10, IL-12p70, IL-1\u03b1, IL-1\u03b2, and TNF-\u03b1 upon TCR-dependent T-cell stimulation with CD3-coated beads but also superantigens. The IFN-\u03b3 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&amp;gt;C mutation in the interferon-\u03b3 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-\u03b3 resulted in proper upregulation of high-affinity Fc\u03b3RI (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-\u03b3. Conclusion: A detailed phenotypic and functional immunological examination is urgently required to determine the cause of a clinically relevant immunodeficiency, despite detailed genetic analyses. <\/jats:p>","DOI":"10.1159\/000530844","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T21:00:44Z","timestamp":1693861244000},"page":"914-931","source":"Crossref","is-referenced-by-count":1,"title":["Mycobacterium avium Complex Infections: Detailed Phenotypic and Functional Immunological Work-Up Is Required despite Genetic 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