CD19, immunoglobulin level, and varied anti-cytokine autoantibodies underline dichotomous susceptibility to types of infection in patients with thymomas.

Authors

Zhaohong Tan, Areum Shin, Rachel Ying Min Tan, Dongling Wang, Chiung-Hui Huang, Sharada Ravikumar, Liang En Wee, Yvonne Fu Zi Chan, Ying Ying Chua, Sen Hee Tay, Anindita Santosa, Gladys Gek Yen Tan, Doo Ri Kim, Hyun-Il Gil, Jae-Hoon Ko, Sun Hye Shin, Byung Woo Jhun, Siew Hoon Sim, Yae-Jean Kim, Louis Yi Ann Chai

Published in

Frontiers in immunology. Volume 17. Pages 1824198. Epub Jul 10, 2026.

Abstract

Increased susceptibility to infections is observed in patients with thymomas. These have been invariably attributed to Good syndrome with hypogammaglobulinemia, but there is noticeable heterogeneity in clinical presentation. We clinically and immunophenotypically characterized the infective susceptibilities encountered in these patients.
Of thymoma patients recruited from Singapore and South Korea, their infection types were correlated against immunological parameters, including IgG, IgM, IgA, CD19+ B cells, and CD4+ T cells, and the presence of neutralizing anti-cytokine autoantibodies using direct ELISA. Lymphocyte subset immunophenotyping was performed. Ascertainment of immune signaling pathway disruption was through serum switch experiments. Respective immune signal outputs were probed using Western blotting.
A total of 15 thymoma patients (median age, 54 years; 13 men [87%]) were clustered into two groups with discernible differences in infective manifestations. In one group, nine patients (60%) had recurrent/severe viral or Pneumocystis jirovecii infections. These patients had low immunoglobulins and CD19+ B cells. The second group of six patients (40%) had difficult-to-treat non-tuberculous mycobacterium (NTM) or invasive bacterial or fungal infections. They had normal immunoglobulins levels and possessed autoantibodies against interleukin (IL-)-12, IL--23, or interferon-alpha (IFN-α), which consisted of anti-IFN-α2 and anti-IFN-ω subtypes. The autoantibodies consisted of a heterogeneous spread across IgG1 to IgG4 subclasses. These anti-IL--12, anti-IL--23, and anti-IFN-α autoantibodies were neutralizing and compromised various phosphorylated-STAT signaling pathways that are critical in host anti-pathogen response.
The dichotomy of infective manifestations (viral/PJP versus NTM/invasive bacteria/fungal) underlies distinct and novel immune susceptibility beyond the classic Good syndrome label in thymoma patients, with implications for different approaches to clinical management.

PMID:
42500663
Bibliographic data and abstract were imported from PubMed on 25 Jul 2026.

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