Uveitis in DiGeorge syndrome: a case of autoimmune ocular inflammation in a patient with deletion 22q11.2

Abstract

Purpose: Del22q11.2, also known as DiGeorge syndrome, has a spectrum of ocular, facial and systemic features. Despite features of T cell dysfunction, infection and autoimmunity (including juvenile idiopathic arthritis), uveitis has not been described in patients with DiGeorge syndrome.

Methods: We describe a case of a 25-year-old male with bilateral granulomatous panuveitis who after initial investigation and treatment for an infectious cause was determined to have autoimmune-related uveitis with evidence on clinical, laboratory and imaging assessments suggestive of ocular sarcoidosis.

Results: The patient was found to have a normal T cell count and T cell proliferative response that was compared to a control patient, and phenotypes determined by flow cytometry were normal. However, the CD4/CD8 ratio in this patient was slightly lower than normal and the number of CD28 negative T cells, in both CD4 and CD8 populations, were significantly higher than a control.

Conclusions: The significance of these T cell abnormalities is unknown in the context of this patient's uveitis but is suggestive of a role in autoimmunity, which is a known phenomenon in del22q11.2 syndrome, although autoimmune-related uveitis is not a previously described feature.

FIGURE 1

Anterior segment photos of the right and left eyes demonstrate conjunctival injection in both eyes, irregular pupils due to posterior synechiae and mild flare in the anterior chamber.

FIGURE 2

(A) Color photos of the right and left eyes demonstrate optic disc edema and splinter hemorrhages, as well as tortuous vessels and deep choroidal lesions (arrow, most easily visible inferior to the nerve heads). There is trace vitreous haze OD. (B) Fluorescein angiogram of the right and left eyes showing hyperfluorescence of the optic nerves and an area of leakage near the fovea corresponding to a retinal cyst seen by OCT (C)

FIGURE 3

Cytogenetic analysis by fluorescence in-situ hybridization (FISH). The DiGeorge critical region is detected by the red probe (lower left), a distal 22q gene (ARSA) is detected by the green probe (lower left and upper). There is one normal #22 chromosome (both red and green signals, lower left) and one abnormal #22 chromosome deleted for the DGS/VCFS region with only a green signal (upper).

FIGURE 4

(A) T cell proliferative response to phytohemaglutinin (PHA) and anti-TCR stimulation. Peripheral blood mononuclear cells (PBMCs) were isolated from fresh blood from the patient and a healthy donor. PBMCs were stimulated with PHA or anti-CD3 with without anti-CD28 at different dosages as depicted in the figure. Tritium labeled thymidine incorporation was used to measure proliferative response of T cells to the stimuli. There was no difference in T cell proliferation between the patient and a healthy control. (B) Increased CD28 negative T cells in patient compared to that in normal control. Whole blood samples were analyzed by a 4-color flow cytometry staining using FITC-CD4, PE-CD28, PE-CY7-CD3 and APC-CD8 antibodies (BD Biosciences, CA). The T cell staining was analyzed using FlowJo software (TriStar, San Jose, CA). CD28 negative T cells were gated based on CD3+CD4+CD28- and CD3+CD8+CD28- triple staining. CD28 negative T cells in both CD3+CD4+ and CD3+CD8+ T cells were much higher in DGS (DiGeorge syndrome) patient than in a normal control donor. A patient with a diagnosis of NK (natural killer cell) lymphocytosis and multiple autoimmune diseases also showed increased CD28 negative T cells.