Effects of infliximab on lung and circulating natural killer cells, CD56+ T cells and B cells in sarcoidosis

Abstract

BackgroundTumour necrosis factor α (TNF-α) is pivotal in sarcoid granuloma formation, and inhibitors of TNF-α offer an attractive third-line treatment option in sarcoidosis. The sarcoid inflammation is characterised by an exaggerated T helper 1 response, and evidence indicates a contribution of dysregulated and/or deficient NK (natural killer) cells, CD56+ T cells and B cells.ObjectivesInsight into how TNF-α inhibitors influence these cells may provide more information on inflammatory mechanisms in sarcoidosis and improve understanding of such treatment. We therefore evaluated treatment effects of the TNF-α inhibitor infliximab on lung and peripheral blood (PB) NK, CD56+ T cells and B cells.MethodsFifteen patients were assessed with PB samples, spirometry and CT scan, and 11 of them also underwent bronchoalveolar lavage (BAL) close to start of infliximab treatment. These investigations were repeated after 6 months of treatment.ResultsTwelve out of 15 patients disclosed a clinical improvement at follow-up. Median percentage of BAL fluid (BALF) CD56+ T cells increased while a decrease was seen in PB (p<0.05 and 0.005, respectively). No significant changes were observed for NK cells. There was a trend towards increased median percentage of PB B cells (p=0.07), and a negative correlation was observed between PB and BALF B cells after treatment (p<0.05).ConclusionIn conclusion, 6 months of infliximab treatment in patients with sarcoidosis, of whom the majority benefited from the treatment, influenced immune cells in the lung and circulation differently, highlighting the importance of investigating several compartments concomitantly when evaluating treatment effects on the inflammatory activity.

Lymphopenia and high Ki-67 expression in peripheral blood CD4+ and CD8+ T cells associate with progressive sarcoidosis

“…Data are presented as n or median (25th–75th percentile). Training denotes patients participating in a 3-month training programme, described in reference number 21. Treatment denotes treatment at third follow-up.EPM, extrapulmonary manifestation; F, female; M, male; Scadding, radiographic extent of sarcoidosis assessed by chest X-ray using Scadding staging system (0–IV).…”

“…All patients except for one were also screened for hypercalciuria. Bronchoscopy with BAL was performed as previously described21 22 and baseline blood samples were drawn within a couple of weeks after referral. The patients were then followed and blood samples were drawn at median 6 months (first follow-up) and 11 months (second follow-up) after baseline sampling.…”

“…Data are presented as n or median (25th-75th percentile). Training denotes patients participating in a 3-month training programme, described in reference number 21. Treatment denotes treatment at third follow-up.…”