Several studies have implicated a role of inflammation in the pathogenesis of lung damage in idiopathic pulmonary fibrosis (IPF). Parenchymal lung damage leads to defects in mechanics and gas exchange and clinically manifests with exertional dyspnea. Investigations of inflammatory cells in IPF have shown that eosinophils, neutrophils and CD 8+ TLs may be associated with worse prognosis. We wished to investigate by quantitative immunohistochemistry infiltrating macrophages, neutrophils and T lymphocytes (TLs) subpopulations (CD 3+ , CD 4+ and CD 8+ ) in lung tissue of patients with IPF and their correlation with lung function indices and grade of dyspnoea. Methods Surgical biopsies of 12 patients with IPF were immunohistochemically stained with mouse monoclonal antibodies (anti-CD 68 for macrophages, anti-elastase for neutrophils, and anti-CD 3 , anti-CD 4 , anti-CD 8 for CD 3+ TLs, CD 4+ TLs, and CD 8+ TLs respectively). The number of positively stained cells was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor). Cell numbers were expressed in percentage of immunopositive nuclear surface in relation to the total nuclear surface of infiltrative cells within the tissue (labeling Index). Correlations were performed between cell numbers and physiological indices [FEV 1 , FVC, TLC, D LCO, PaO 2 , PaCO 2 and P(A-a)O 2 )] as well as dyspnoea scores assessed by the Medical Research Council (MRC) scale. Results Elastase positive cells accounted for the 7.04% ± 1.1 of total cells, CD 68+ cells for the 16.6% ± 2, CD 3+ TLs for the 28.8% ± 7, CD 4+ TLs for the 14.5 ± 4 and CD 8+ TLs for the 13.8 ± 4. CD 8+ TLs correlated inversely with FVC % predicted (r s = -0.67, p = 0.01), TLC % predicted (r s = -0.68, p = 0.01), DLCO % predicted (r s = -0.61, p = 0.04), and PaO 2 (r s = -0.60, p = 0.04). Positive correlations were found between CD 8+ TLs and P(A-a)O 2 (r s = 0.65, p = 0.02) and CD 8+ TLs and MRC score (r s = 0.63, p = 0.02). Additionally, CD 68+ cells presented negative correlations with both FVC % predicted (r s = -0.80, p = 0.002) and FEV 1 % predicted (r s = -0.68, p = 0.01). Conclusion In UIP/IPF tissue infiltrating mononuclear cells and especially CD 8+ TLs are associated with the grade of dyspnoea and functional parameters of disease severity implicating that they might play a role in its pathogenesis.
Open Access Research CD Tlymphocytes in lung tissue from patients with idiopathic 8+ pulmonary fibrosis 1 21 2 Zoe Daniil, Panagiota Kitsanta, George Kapotsis, Maria Mathioudaki, 1 34 Androniki Kollintza, Marilena Karatza, Joseph MilicEmili, 1 1 Charis Roussosand Spyros A Papiris*
1 Address: Departmentof Critical Care and Pulmonary Services, National and Capodistrian University of Athens, "Evangelismos" Hospital, Athens, 2 3 Greece, PathologyDepartment, "Evangelismos" Hospital, Athens, Greece,Hematology Department, "Evangelismos" Hospital, Athens, Greece 4 and MeakinsCristieLaboratories, McGill University, Montreal, Quebec, Canada Email: Zoe Daniil zdaniil@med.uth.gr; Panagiota Kitsanta Panagiota.Kitsanta@sth.nhs.uk; George Kapotsis gkapotsis@hotmail.com; Maria Mathioudaki mmathioudaki@hotmail.com; Androniki Kollintza akollin@hotmail.com; Marilena Karatza mkaratza@otenet.gr; Joseph MilicEmili Joseph.MilicEmily@mcgill.ca; Charis Roussos Croussos@med.uoa.gr; Spyros A Papiris* papiris@otenet.gr * Corresponding author
Abstract Background:Several studies have implicated a role of inflammation in the pathogenesis of lung damage in idiopathic pulmonary fibrosis (IPF). Parenchymal lung damage leads to defects in mechanics and gas exchange and clinically manifests with exertional dyspnea. Investigations of inflammatory cells in IPF have shown that eosinophils, neutrophils and CD 8+ TLs may be associated with worse prognosis. We wished to investigate by quantitative immunohistochemistry infiltrating macrophages, neutrophils and T lymphocytes (TLs) subpopulations (CD, CDand CD) in lung tissue of patients with 3+ 4+8+ IPF and their correlation with lung function indices and grade of dyspnoea. Methods:Surgical biopsies of 12 patients with IPF were immunohistochemically stained with mouse monoclonal antibodies (anti-CDfor macrophages, anti-elastase for neutrophils, and anti-CD , anti-CD , anti-CDfor CDTLs, 68 34 83+ CD TLs,and CDTLs respectively). The number of positively stained cells was determined by observer-interactive 4+ 8+ computerized image analysis (SAMBA microscopic image processor). Cell numbers were expressed in percentage of immunopositive nuclear surface in relation to the total nuclear surface of infiltrative cells within the tissue (labeling Index). Correlations were performed between cell numbers and physiological indices [FEV , FVC, TLC,DLCO, PaO , PaCO 1 22 and P(A-a)O )] as well as dyspnoea scores assessed by the Medical Research Council (MRC) scale. 2 Results:Elastase positive cells accounted for the 7.04% ± 1.1 of total cells, CDcells for the 16.6% ± 2, CDTLs for 68+ 3+ the 28.8% ± 7, CDTLs for the 14.5 ± 4 and CDTLs for the 13.8 ± 4. CDTLs correlated inversely with FVC % 4+ 8+8+ predicted (r= -0.67, p = 0.01), TLC % predicted (r= -0.68, p = 0.01), DLCO % predicted (r= -0.61, p = 0.04), and s ss PaO (r =-0.60, p = 0.04). Positive correlations were found between CDTLs and P(A-a)O(r =0.65, p = 0.02) and 2 s8+ 2s CD TLsand MRC score (r= 0.63, p = 0.02). Additionally, CDcells presented negative correlations with both FVC 8+ s68+ % predicted (r= -0.80, p = 0.002) and FEV% predicted (r= -0.68, p = 0.01). s 1s Conclusion:In UIP/IPF tissue infiltrating mononuclear cells and especially CDTLs are associated with the grade of 8+ dyspnoea and functional parameters of disease severity implicating that they might play a role in its pathogenesis.
Page 1 of 8 (page number not for citation purposes)