Biallelic TTC7A mutation has been implicated in Multiple Intestinal Atresia- Severe Combined Immunodeficiency (MIA-SCID), as well as Very Early Onset Inflammatory Bowel Disease (VEO-IBD).We present a patient with a TTC7A (R163W) mutation presenting with Crohn's disease at 9 years of age. Whole blood was obtained from the patient, PBMCs were then isolated and stimulated with pokeweed, PBS, CD79b, or IL-4/CD40. The samples were then stained and for CXCR4 and CCR7. In the second Stimulation Assay, CD3/28 was used in addition to the previous stimulants, and the cells were stimulated overnight. For the Proliferation Assay, PBMCs were labeled with CFSE, stimulated with CD3/28, and incubated for 3 days at 37ºC. The Stimulation Assay indicated that the patient exhibits lower levels of baseline CXCR4 expression compared to controls. In the healthy control, stimulation resulted in down-regulation of CXCR4, while in the TTC7A patient, CXCR4 was up-regulated. CCR7 expression does not change much in response to stimulation in a healthy control, but down-regulates in the TTC7A patient and up-regulates in the TTC7A carrier mother. The proliferation assay revealed that the TTC7A patient had increased proliferation of T cells compared to the healthy control and mother. TTC7A plays a role in apicobasal polarity of enterocytes, as well as the migration and adhesion capabilities of lymphocytes. This case study shows that carrying one mutant TTC7A allele results in immunologic abnormalities, especially in the molecules that play a role in lymphocyte migration.
Virginia Commonwealth University, Medical College of Virginia