Chromosome 18q deletion syndrome (18q del) is a rare genetic disorder that affects approximately 1 in 40,000 to 55,000 people and is caused by a deletion of genetic material on the long arm of chromosome 18. This genetic abnormality disrupts normal growth and development and, more seriously, may affect the functioning of the immune system. Patients with chromosome 18q deletion syndrome typically have a humoral immunodeficiency or a common variable immunodeficiency (CVID-like) phenotype, which is characterized by low levels of immunoglobulins (antibodies) in the blood, compromising the body’s ability to effectively fight infections.
Now, however, in a study recently published in the journal Journal of Clinical ImmunologyResearchers at Tokyo Medical and Dental University (TMDU) and Kagoshima University have identified a previously undocumented manifestation among patients with del 18q syndrome: late-onset combined immunodeficiency (LOCID), which affects both B and T cells. This novel finding underscores the critical importance of routinely assessing B and T cell functionality in individuals with del 18q syndrome.
Elaborating further on this novel finding, Professor Kanegane says: “In this study, we found two patients with chromosome 18q syndrome who presented LOCID, which, to our knowledge, has not yet been reported in patients with the syndrome.”
Patient 1 was a 29-year-old man diagnosed with 18q deletion syndrome. Despite having few infections initially, he developed Pneumocystis pneumonia (PCP). Array-based comparative genomic hybridization (CGH) analysis showed a deletion in the chromosomal region 18q21.32-q22.3.
Patient 2 was a 48-year-old woman who had not previously been diagnosed with 18q deletion syndrome. However, she was diagnosed with granulomatous lymphadenitis and a biopsy of her lymph nodes revealed a loss of 18q21.33-qter.
Both patients presented with hypogammaglobulinemia, characterized by abnormally low levels of immunoglobulins (IgG, IgA, IgM, and IgE). Patient 1’s serum immunoglobulin levels were significantly below normal ranges. He reported IgG levels of 188 mg/dL (normal: 870-1,700 mg/dL), IgA of 105 mg/dL (normal: 110-410 mg/dL), IgM of 26 mg/dL (normal: 33-190 mg/dL), and IgE of <5 IU/mL (normal: 232 IU/mL). His CD4 count was 1.5 mg/dL (normal: 1.5 mg/dL).+ T cells had a reduced percentage of naive T cells, accounting for only 3.58% of total CD3.+CD4+ cell population. In addition, their T cell receptor excision circles (TREC) levels and Ig κ deletion recombination excision circle (KREC) levels were extremely low, 25.27 copies/105 cells (normal: >565 copies/105 cells) and 93.36 copies/105 cells (normal: ≥456 copies/105 cells) respectively, indicating poor T cell production.
Similar conditions were observed in patient 2, who reported IgG of 8 mg/dl, IgA of 9 mg/dl, IgM of 131 mg/dl and IgE of 0.3 IU/ml. His CD4 count+ Naive T cells and CD4+ T cells were exhausted and naive T cells accounted for only 6% of CD3.+CD4+ Cell population. Their TREC levels were 0 copies/105 cells and their KREC levels were 11.4 copies/105 cells.
It is important to note that CD4+ and CD8+ T cells failed to divide in response to phytohemagglutinin (PHA) stimulation, indicating severe T cell functional impairment in both patients.
Based on their immune profiles and clinical history, both were diagnosed with LOCID, a condition in which both the humoral (antibody-mediated) and cell-mediated immune responses were impaired, making them highly susceptible to infections.
This new finding is significant as Dr. Tomomasa, co-author of this study, states, “While cases involving deletion of the same region as those of the two patients presented in this study have been previously reported, patients with 18q deletion syndrome developing LOCID have never been reported. We speculate that these patients simply have not yet developed LOCID or may not have been adequately screened for it.”
Based on these results, the researchers recommend annual cellular and humoral immunity testing in patients with 18q deletion syndrome. This proactive approach may allow for early detection of combined immune deficiencies, facilitating timely interventions and personalized treatment strategies. Ultimately, this regular monitoring may significantly improve clinical outcomes and enhance the quality of life of individuals diagnosed with 18q deletion syndrome.