# Good’s Syndrome Mirrors a Combined Immunodeficiency with Anti-Cytokine Antibodies in the Total Absence of B Cells

## TL;DR

Good’s Syndrome is a rare immune deficiency characterized by severe B-cell loss and anti-cytokine antibodies, likely caused by thymoma-related immune dysregulation.

## Contribution

This study identifies persistent anti-cytokine antibodies and profound B-cell loss in Good’s Syndrome, suggesting a thymoma-associated breakdown in immune tolerance.

## Key findings

- GS patients have complete absence of B-cells in peripheral blood and lymphoid tissues.
- High titers of anti-cytokine antibodies, including anti-interferons, persist in GS patients.
- No monogenic cause was found, suggesting immune dysregulation is thymoma-associated.

## Abstract

Good’s Syndrome, an adult-onset immune deficiency, has been traditionally grouped with humoral immune deficiencies such as Common Variable Immune Deficiency (CVID) and X-linked agammaglobulinemia (XLA) despite the unique presence of the thymic neoplasm, late age of onset, frequent opportunistic infections and multiple cytopenias. Low prevalence and sporadic reporting have limited investigative efforts. We conducted a prospective, multimodal, study to establish the GS phenotype in the absence of severe infections. A previously characterized cohort of GS patients was compared to healthy individuals and those diagnosed with CVID or XLA using serology, immunophenotyping and histopathology. We also attempted to establish an inborn cause of the immune deficiency with HLA typing and Whole Exome Sequencing. GS patients exhibited severe hypogammaglobulinemia, a complete absence of B-cells in the peripheral blood and in biopsied primary and secondary lymphoid tissues. Total lymphocytes and CD4 T-cell counts were markedly reduced in GS but with intact T-cell proliferative capacity to in vitro mitogen and lectin stimulation. Autoantibody profiling identified high titers of antibodies in GS patient plasma to several cytokines, notably anti-interferons, which persisted for several years. These antibodies overlapped with those observed in thymoma patients without GS. We demonstrate that GS involves profound B-cell-loss, extending beyond blood to the lymphoid tissue, however plasma cells and circulating anti-cytokine antibodies can persist for years. In the absence of a unifying monogenic defect, the findings are suggestive of a thymoma-associated breakdown in central tolerance driving the immune dysregulation and deficiency seen in GS.

The online version contains supplementary material available at 10.1007/s10875-026-01992-5.