18q Deletion Syndrome Presenting with Late-Onset Combined Immunodeficiency

Abstract

Patients with chromosome 18q deletion syndrome generally experience hypogammaglobulinemia. Herein, we describe two patients with chromosome 18q deletion syndrome who presented with late-onset combined immune deficiency (LOCID), which has not been previously reported. Patient 1 was a 29-year-old male with 18q deletion syndrome, who was being managed for severe motor and intellectual disabilities at the Yamabiko Medical Welfare Center for 26 years. Although the patient had few infections, he developed Pneumocystis pneumonia at the age of 28. Patient 2, a 48-year-old female with intellectual disability and congenital malformations, was referred to Tokyo Medical and Dental University Hospital with abnormal bilateral lung shadows detected on her chest radiography. Computed tomography showed multiple lymphadenopathies and pneumonia. A lymph node biopsy of the inguinal region revealed granulomatous lymphadenitis, and a chromosomal examination revealed 18q deletion. Array-based genomic hybridization analysis revealed deletion at 18q21.32-q22.3 for patient 1 and at 18q21.33-qter for patient 2. Immune status work-up of the two patients revealed panhypogammaglobulinemia, decreased number of memory B cells and naïve CD4⁺ and/or CD8⁺ cells, reduced response on the carboxyfluorescein diacetate succinimidyl ester T-cell division test, and low levels of T-cell receptor recombination excision circles and Ig κ-deleting recombination excision circles. Consequently, both patients were diagnosed with LOCID. Although patients with 18q deletion syndrome generally experience humoral immunodeficiency, the disease can be further complicated by cell-mediated immunodeficiency, causing combined immunodeficiency. Therefore, patients with 18q deletion syndrome should be regularly tested for cellular/humoral immunocompetence.

Keywords: Pneumocystis pneumonia; 18q deletion syndrome; Array-based comparative genomic hybridization; Common variable immunodeficiency; Late-onset combined immunodeficiency.

Fig. 1

Radiological findings. A: (Patient 1) Chest X-ray revealing atelectasis in the right upper lobe. The right costophrenic angle is dull, with a granular shadow in the entire lung field. B: (Patient 1) Chest CT, showing slight compression of the right upper bronchus, presence of an air bronchogram in the right upper lobe, and consolidations in the left lung, which are believed to be inflammatory changes, suggesting that the patient has pneumonia. Granular shadows are observed in the lungs. C: (Patient 2) Chest X-ray showing abnormal bilateral lung shadows. D: (Patient 2) Chest CT showing mottled frosted shadows and irregular nodular shadows in both lungs

Fig. 2

T-cell receptor Vb repertoire analysis. A: TCRVβ analysis of CD4⁺ T cells. The blue, red, and green bars indicate Vβ-positive cells in the T cells from the controls, Patient 1, and Patient 2, respectively. B: TCRVβ analysis of CD8⁺ T cells. The blue, red, and green bars indicate Vβ-positive cells in the T cells from the controls, Patient 1, and Patient 2, respectively

Fig. 3

Results of T-cell proliferation assay. In the CFSE (carboxyfluorescein diacetate succinimidyl ester) T-cell proliferation test, CD4⁺ and CD8⁺ T lymphocytes do not undergo cell divisions in response to stimulus with phytohemagglutinin and are not activated compared to the control group. The blue and red shades indicate unstimulated and stimulated statuses, respectively. The percentages of cells after the application of stimuli are noted in the box

Fig. 4

Results of comparative genomic hybridization and single-nucleotide polymorphism microarray analysis. The results of the CGH+SNP microarray for chromosome 18 show deletion from 18q21.32 to 18q22.3 (A: patient 1), and from 18q21.33 to 18qter (B: patient 2)