Humoral immunity in phenotypes of chronic lung allograft dysfunction: A broncho-alveolar lavage fluid analysis

• Published in: Transplant immunology 2016-09, Vol.38, p.27-32
• Main Authors: Vandermeulen, Elly, Verleden, Stijn E., PhD, Bellon, Hannelore, Ruttens, David, MD, Lammertyn, Elise, Claes, Sandra, Vandooren, Jennifer, PhD, Ugarte-Berzal, Estafania, Schols, Dominique, PhD, Emonds, Marie-Paule, MD, PhD, Van Raemdonck, Dirk E., MD, PhD, Opdenakker, Ghislain, MD, PhD, Verleden, Geert M., MD, PhD, Vos, Robin, MD, PhD, Vanaudenaerde, Bart M., PhD
• Format: Article
• Language: English
• Subjects: Adult; Airway Remodeling; Allergy and Immunology; Antibody mediated rejection; Bronchiolitis Obliterans - diagnosis; Broncho-alveolar lavage fluid; Bronchoalveolar Lavage - methods; Bronchoalveolar Lavage Fluid - immunology; Chronic Disease; Chronic lung allograft dysfunction; Complement C4b - metabolism; Extracellular Matrix - metabolism; Female; Graft Rejection - diagnosis; Humans; Immunity, Humoral; Immunoglobulins - metabolism; Lung - metabolism; Lung - pathology; Lung Transplantation; Male; Matrix Metalloproteinase 9 - metabolism; Middle Aged; Peptide Fragments - metabolism; Phenotype; Transplantation, Homologous
• ISSN: 0966-3274; 1878-5492
• DOI: 10.1016/j.trim.2016.08.004

Abstract Background Recently, antibody mediated rejection (AMR) has been associated with a higher incidence of chronic lung allograft dysfunction (CLAD) and mortality after lung transplantation (LTx). We investigated markers related to AMR and matrix remodeling in CLAD, with special attention for its two phenotypes being bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (rCLAD). Methods Immunoglobulins (IgA, IgE, IgG1 –IgG4 , total IgG and IgM) and complement (C4d and C1q) were quantified in lung lavage samples at the moment of BOS (n = 15) or RAS (n = 16) diagnosis; and were compared to stable transplant patients who served as control (n = 14). Also, airway remodeling and metalloproteinases (MMPs) were investigated via zymography and gelatin degradation. The presence of DSA was additionally assessed in blood. Results Total IgG, IgG1 -IgG4 and IgM were increased in rCLAD versus control (p < 0.001) and BOS patients (p < 0.01). IgA and IgE were increased in rCLAD compared to control (respectively p < 0.05 and p < 0.01), but not to BOS. Total IgG and IgE were increased in BOS versus control (respectively p < 0.01 and p < 0.05). Complement proteins were exclusively present in rCLAD and correlated positively with immunoglobulins. Additionally, in blood, DSA were more present in rCLAD (p = 0.041). MMP-9 levels increased in RAS and BOS versus control (p < 0.001) and MMP-9 induced gelatin degradation was only increased in BOS compared to control (p < 0.01). Conclusion We demonstrated increased levels of immunoglobulins and complement proteins dominantly present in rCLAD. This leads to the belief that antibodies and AMR might play a more important role in rCLAD compared to BOS. Therefore, anti B-cell therapy could offer beneficial therapeutic effects in patients diagnosed with rCLAD, which needs further research.