Researchers have found a new link between chromosome 18q deletion syndrome and late-onset combined immunodeficiency (LOCID). This discovery challenges the previous belief that 18q deletion syndrome only affects B cells and antibody production. The study emphasizes the importance of regular immune function testing in patients with 18q deletion syndrome for early detection and better management.
Chromosome 18q deletion (18q del) syndrome is a rare genetic disorder affecting around 1 in 40,000 to 55,000 individuals. It occurs due to the deletion of genetic material on the long arm of chromosome 18. This genetic abnormality disrupts normal growth and development and can negatively impact the immune system’s function. People with 18q del syndrome often show signs of humoral immunodeficiency or a common variable immunodeficiency (CVID)-like condition, characterized by low levels of antibodies in the blood, which weakens the body’s ability to fight infections.
Recently, in a study published in the Journal of Clinical Immunology, researchers from Tokyo Medical and Dental University (TMDU) and Kagoshima University identified a new aspect in patients with 18q del syndrome – late-onset combined immunodeficiency (LOCID), affecting both B and T cells. This novel finding underscores the importance of regularly assessing both B and T cell function in individuals with 18q del syndrome.
Explaining this new discovery further, Professor Kanegane states, “In this study, we found two patients with chromosome 18q del syndrome who had LOCID, which, to our knowledge, has not been reported before in these patients.”
The first patient was a 29-year-old man with 18q del syndrome. Although initially experiencing few infections, he later developed Pneumocystis pneumonia (PCP). Genetic analysis revealed a deletion in the 18q21.32-q22.3 chromosome region.
The second patient was a 48-year-old woman previously undiagnosed with 18q del syndrome. However, she was diagnosed with granulomatous lymphadenitis, and tissue analysis showed a loss of 18q21.33-qter.
Both patients had low levels of immunoglobulins (IgG, IgA, IgM, and IgE). The first patient had significantly below-normal serum immunoglobulin levels: IgG 188 mg/dL, IgA 105 mg/dL, IgM 26 mg/dL, and IgE <5 IU/mL. His CD4+ T cells had a reduced percentage of naïve T cells, representing only 3.58% of the total CD3+CD4+ cell population. Additionally, his T-cell production indicators were notably low, indicating poor T-cell generation.
Similar results were observed in the second patient, with IgG 8 mg/dL, IgA 9 mg/dL, IgM 131 mg/dL, and IgE 0.3 IU/mL. Her CD4+ T cells and naive CD4+ T cells were depleted, with naïve T cells making up only 6% of the CD3+CD4+ cell population. Her T-cell production markers were also very low.
Both patients’ CD4+ and CD8+ T cells showed poor division in response to stimulation, indicating significant T-cell dysfunction in both cases.
Based on their immune profiles and medical history, both patients were diagnosed with LOCID, where both humoral and cell-mediated immune responses were compromised, making them highly vulnerable to infections.
This new discovery holds great importance, as Dr. Tomomasa, a co-author of the study, mentions, “While previous cases with deletion in the same region as these two patients have been reported, cases of 18q del syndrome leading to LOCID have not been documented. It is possible that these patients have not yet developed LOCID or were not thoroughly evaluated for it.”
As a result of these findings, the researchers recommend yearly testing of both cellular and humoral immunity in individuals with 18q del syndrome. This proactive approach can enable early identification of combined immune deficiencies, allowing for timely interventions and personalized treatment plans. Regular monitoring can significantly enhance clinical outcomes and improve the quality of life for individuals with 18q del syndrome.
