Release of B Cell-Activating Factor of the TNF Family in Bronchoalveolar Lavage from Behçet Disease with Pulmonary Involvement

Agnès Hamzaoui,Kamel Hamzaoui,Fayçal Hai Sassi,Hanene Chelbi

doi:10.4161/oxim.3.2.11149

Abstract

Pulmonary artery aneurysms, arterial and venous thrombosis, pulmonary infarction, recurrent pneumonia, bronchiolitis obliterans organized pneumonia, and pleurisy are the main features of pulmonary involvement in Behçet's disease. The objective of this study was to investigate the production of B cell-activating factor of the TNF family (BAFF), an important regulator of B-cell survival and immunoglobulin class-switch recombination, in bronchoalveolar lavage (BAL) fluid from BD patients having pulmonary manifestation. Bronchoalveolar lavage (BAL) was performed in 15 BD patients with pulmonary manifestation and 18 BAL from healthy controls. Concentrations of B cell-active cytokines, including BAFF, IL-6, and IL-13, were measured by using specific ELISA and cytometric bead array assays. Levels of BAFF protein were significantly increased in BAL fluid from active BD [109 +/- 21.78 pg/mL] compared with those oh healthy controls [4.83 +/- 1.75 pg/mL; P<0.0001]. In the BAL fluid, BAFF levels were significantly correlated with absolute numbers of total cells [r = 0.823; P<0.0001], lymphocytes [r = 0.709; P<0.0001], neutrophils [r = 0.809; P<0.0001] and macrophages [r = 0.742; P<0.0001]. Normalization to albumin indicated that BAFF production occurred locally in the airways. BAFF levels were also significantly correlated with the other B cell-activating cytokines IL-6 [r = 0.882, P<0.001] and IL-13 [r = 0.659, P<0.001].The antigen-induced production of BAFF in the lung of active BD with pulmonary manifestations might contribute to immunoglobulin synthesis by B cells. The cells residing in the lung might affect each other through BAFF.

Highlights

Behçet disease (BD) is a multi-system inflammatory disorder, currently classified as a vasculitis
We report correlations between bronchoalveolar lavage (BAL)-B-cell-activating factor of the TNF family (BAFF) levels and cell counts and that the levels of production were highly correlated with the appearance of the other B-cell-activating cytokines IL-6 and IL-13
Using BAL fluid data obtained from BD patients, we found that the levels of BAFF were strongly correlated with the levels of IL-6 (r = 0.882, p < 0.001) (Fig. 3B) and IL-13 (r = 0.659, p < 0.0001) (Fig. 3C)

Summary

Introduction

Behçet disease (BD) is a multi-system inflammatory disorder, currently classified as a vasculitis. Many studies have investigated genetic aspects and immunologic features of the disorder. Immunological studies were needed in inflammatory sites as the lung. The International Study Group for Behçet Disease has established diagnostic criteria for BD, which make recurrent oral ulcers a mandatory finding, along with two of the four: recurrent genital ulcers, eye involvement, skin lesions and pathergy.[1] While various tissue types such as blood vessel, eye, skin, mucosa, joint or central nervous system (CNS), may be affected during the course of BD, lung involvement, remains one of the most serious complications of the disease.[2] Large vessel vasculitis in BD may affect the pulmonary arteries, the aorta and other major peripheral vessels.[3,4,5,6]

Objectives

Methods

Results