PURPOSE: NF-kB/p65 is critical for the control of a variety of cellular processes including activation, proliferation and cytokine production. Expression of p65 protein in CD4+ T-cells is significantly reduced in a subgroup of sarcoidosis patients. Here, we compared clinical variables of disease activity between groups of sarcoid patients that exhibited normal or reduced p65 levels in their CD4+ T-cells. Associations between p65 levels and absolute numbers of B- and T-cells were also investigated.
METHODS: A retrospective chart review of 43 patients with known reduced (n=21) or normal (n=22) p65 levels was performed. Clinical data including demographics, number of organs involved, disease activity, radiologic staging, and therapy regimen was analyzed. Absolute lymphocyte counts were calculated, in patients and controls, from the CBC/differential obtained on a hematologic analyzer, and the percentages of CD4+ or CD19+ cells obtained by FACS.
RESULTS: Compared to what was observed in p65 competent patients, multiple (≥3) organ involvement (41% vs. 13%, P= 0.056) and stage IV pulmonary sarcoidosis (41% vs. 4%, P=0.007) were predominantly seen in the p65 deficient group. p65 deficient patients also had more clinically active (76% vs. 6%, P=0.0023) and worsening disease (42% vs. 9%, P=0.017), and were on more corticosteroids (66% vs. 45%, P=0.00526) or combined therapy (57% vs. 36%,= 0,0013) than patients competent for p65. Finally, p65 deficient patients exhibited significantly reduced absolute CD4+ (259.7 ± 365.8 vs. 673.1 ± 653.4 cells/μl, P=0.009) and CD19+ (1022 ± 936.1 vs. 174 ± 1688 cells/μl, P=0.0048) cell counts in comparison to what was found in p65 competent patients and controls.
CONCLUSION: This study provides the first report comparing clinical, radiological and laboratory variables of sarcoidosis patients based on levels of p65 protein in their T-cells. Patients who had reduced p65 levels exhibited more active/persistent disease, had a greater systemic involvement, responded poorly to steroid therapy and had significantly reduced absolute lymphocyte counts.
CLINICAL IMPLICATIONS: Assessment of p65 levels could help to predict more aggressive disease and poor response to corticosteroids therapy in sarcoidosis.
DISCLOSURE: Laura Barber, No Financial Disclosure Information; No Product/Research Disclosure Information