Methods: Clinical history, conventional laboratory test results, and pulmonary function were obtained from the medical record. Levels of a proliferation-inducing ligand (APRIL) and BAFF were measured in serum and cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence and immunohistochemistry was used to localize leukocytes as well as BAFF, BAFF-R, and Bcl-2 in lung biopsies from patients with CVID ILD. Approval of the institutional review board was obtained.
Results: While markers of lymphoid hyperplasia inversely correlated with APRIL, serum levels of BAFF remained elevated in all patients. Peripheral blood monocytes from CVID patients produced significantly higher levels of BAFF than controls. BAFF was expressed in CVID lungs, exclusively localized with innate immune cells. BAFF receptor (BAFF-R) expression was limited to ectopic pulmonary B cell follicles and corresponded with Bcl-2, an anti-apoptotic protein downstream of BAFF-R.
Conclusions: BAFF production is dysregulated in CVID - it remains elevated in patients with lymphoid hyperplasia and is produced at higher levels in culture. BAFF, BAFF-R, and Bcl-2 localize to ectopic pulmonary follicles in CVID ILD and may contribute to disease progression.