Tu195 - Long-term Evaluation of Good’s Syndrome Reveals a Unique Adult-onset Progressive Immune Deficiency

Vanessa Polito, MDCM FRCPC – Resident, Medicine, McGill University; Christos Tsoukas, CM, MD, FRCP(C), FACP, FCAHS – Professor, Medicine, McGill University

Abstract Text: Good’s syndrome (GS) is a rare immune deficiency of thymoma, hypogammaglobulinemia and recurrent infections. A lack of premorbid and longitudinal data has limited our understanding of a unique human model of adult-onset B-cell lymphopenia. To characterize the clinical evolution and natural progression of disease, we prospectively followed 8 GS patients (6 males:2 females) continually at a single center from 1984 to 2022. Clinical events, complete blood counts, immune phenotyping, and serum immunoglobulin quantification, were captured at semi-annual outpatient visits and all hospitalizations. The mean age at GS diagnosis was 56±12 years with mean follow up of 11.8±10 years. Two individuals died during follow up due to opportunistic infections. At diagnosis, 7/8 patients had significantly low levels of IgG and undetectable IgM. 4/8 had undetectable IgA. Remaining IgG, IgA and IgM continued to decline during follow up. All patients had an absence of peripheral B-cells at diagnosis and in one patient, this absence preceded the IgG decline. Progressively, patients developed lymphopenia[ < 1x109-lymphocytes/L] (n=5), neutropenia[ < 1.9x109/L] (n=3), anemia[ < 13g/L-hemoglobin] (n=4), thrombocytopenia[ < 150x109-platelets/L] (n=3), and CD4 lymphopenia[ < 500-cells/ul] (n=4). A mean decline of 30% in lymphocytes and 25% in platelets was observed 10 years post thymoma diagnosis. Cytopenias progressed with age and correlated with significant clinical outcomes including opportunistic infections. While cytopenias have been noted in previous case studies, this study is the first to show the progressive nature and the temporal association with opportunistic infections. Based on these findings, an evaluation of the bone marrow should be included in the clinical follow-up and studies on the pathophysiology.