Understanding the uncommon:Insights into thymoma associated immunodeficiency

Xin Rong Lim,¹ Bernard Pui Lam Leung,^1,2 Evan Tsien Ming Tan,¹ Faith Li-Ann Chia,¹ Grace Yin Lai Chan,¹ Sze-Chin Tan,¹ Khai Pang Leong,¹ Claire Min-Li Teo,¹ Samuel Shang Ming Lee,¹ Justina Wei Lynn Tan,¹ Bernard Yu-Hor Thong¹

Affiliations:
¹ Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore
² Singapore Institute of Technology

Abstract

Background: Thymoma-associated immunodeficiency (TAI) is a rare, acquired adult-onset immunodeficiency. It includes the classic form of Good syndrome (GS), characterized by thymoma and hypogammaglobulinemia, as well as a non-classic form of GS. This condition leads to specific or combined deficiencies in both B- and T-cells, causing considerable morbidity and mortality, although the underlying immunopathology is still not well understood.
Objective: In this study, we examine the clinical features, laboratory investigations, immunological analysis and treatment outcomes of 21 patients with TAI in our institution, and its associated comorbidities and complications.
Methods: Patients with thymoma and recurrent infections who were followed up in our immunodeficiency clinic between 1 January 1999 and 1 December 2023 were identified. Clinical information, laboratory, treatment and outcome data were extracted from the medical records. Seven patients agreed to provide additional blood samples for anti-cytokine antibodies profiling.
Results: Of the 21 TAI patients, 12 (57.1%) were females and the mean age at diagnosis of TAI was 61.3 ± 9.2 years. 19 patients had classic GS. 12 (57.1%) had underlying bronchiectasis, 5 (23.8%) had sinusitis and 5 (23.8%) developed malignancy other than thymic carcinoma after diagnosis of thymoma. 10 patients (47.6%) developed autoimmune conditions including myasthenia gravis, polymyositis, lichen planus, vasculitis and ulcerative colitis. One patient was found to have high titre of neutralizing anti-interferon alpha antibodies as well as medium titre of neutralizing anti-interleukin 17 antibodies. 9 patients died at a median of 4.2 (IQR 1.98–4.9) years after diagnosis of TAI.
Conclusion: TAI is associated with significant morbidity and mortality. The syndrome leads to a plethora of opportunistic infections, autoimmune complications and malignancy.
Key words: thymoma, immunodeficiency, Good syndrome, hypogammaglobulinemia, anti-cytokine antibody