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

Aunonna Kabir; Vanessa Polito; Christos M Tsoukas

doi:10.1016/j.jaip.2023.12.018

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

J Allergy Clin Immunol Pract. 2024 Mar;12(3):744-752.e3. doi: 10.1016/j.jaip.2023.12.018. Epub 2023 Dec 18.

Authors

Aunonna Kabir¹, Vanessa Polito², Christos M Tsoukas³

Affiliations

¹ Department of Experimental Medicine, McGill University, Montreal, QC, Canada; Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada.
² Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada; Department of Medicine, Division of Allergy and Clinical Immunology, McGill University Health Centre, Montreal, QC, Canada.
³ Department of Experimental Medicine, McGill University, Montreal, QC, Canada; Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada; Department of Medicine, Division of Allergy and Clinical Immunology, McGill University Health Centre, Montreal, QC, Canada. Electronic address: christos.tsoukas@mcgill.ca.

PMID: 38122866
DOI: 10.1016/j.jaip.2023.12.018

Abstract

Background: 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.

Objective: We aimed to determine the clinical and laboratory evolution of 8 adults diagnosed with GS and consecutively evaluated between 1983 and 2023.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Adult-onset combined immune deficiency; B cells; Cytopenia; Good’s syndrome; Hypogammaglobulinemia; Natural history; Opportunistic infection; Thymoma.

MeSH terms

Adult
Agammaglobulinemia* / diagnosis
Agammaglobulinemia* / therapy
Child
Cross-Sectional Studies
Humans
Immunologic Deficiency Syndromes*
Longitudinal Studies
Middle Aged
Primary Immunodeficiency Diseases* / diagnosis
Prospective Studies
Thymoma* / diagnosis
Thymoma* / pathology
Thymus Neoplasms* / diagnosis
Thymus Neoplasms* / pathology