Unraveling the Natural History of Good's Syndrome: A Progressive Adult Combined Immunodeficiency.

Abstract

Good's syndrome (GS) is a rare immune deficiency described almost 6 decades ago. Despite numerous published individual case reports and data collected in cross-sectional studies of small cohorts, the natural history and long-term outcomes of this disease remain unknown. We aimed to determine the clinical and laboratory evolution of 8 adults diagnosed with GS and consecutively evaluated between 1983 and 2023. In this prospective, longitudinal cohort study, newly diagnosed patients with GS were followed through repeated measures of clinical, immune, and hematologic changes, as well as targeted genetic screening. All patients reported a healthy childhood and adolescence with symptom onset during the third or fourth decade of life. All presented to our center with recurrent bacterial sinopulmonary infections, thymoma, hypogammaglobulinemia, and absence of B cells. The median age of GS diagnosis was 57 years. During follow-up, immunoglobin replacement therapy effectively minimized sinopulmonary infections. However, the majority experienced severe and systemic viral or fungal infections, 3 developed basal cell carcinomas, and 5 had progressive bronchiectasis and persistent splenomegaly. The most notable clinical feature was opportunistic infections and in vitro evidence of cellular immune deficiency, which resulted in the death of 2 individuals. We also report a statistically significant, multidecade progressive decline in lymphocytes, platelets, hemoglobin, and red blood cells in our cohort, suggesting gradual bone marrow failure. Knowledge of the unique phenotype and temporal evolution of GS has allowed us to develop a more comprehensive diagnostic framework. It can be investigated as part of broader research into disease pathophysiology.