Understanding the uncommon: Insights into thymoma associated immunodeficiency

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.

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.

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.

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.

TAI is associated with significant morbidity and mortality. The syndrome leads to a plethora of opportunistic infections, autoimmune complications and malignancy.