Interstitial lung disease in systemic sclerosis: comparison of BALF lymphocyte phenotype and DlCO impairment

Abstract

Patients with scleroderma (systemic sclerosis-SSc) frequently develop an interstitial lung disease. The role of lymphocytes in fibrosing alveolitis preceding lung fibrosis has been established. The purpose of this work was to evaluate cell profiles and lymphocyte phenotypes in the bronchoalveolar lavage (BAL) fluid and to correlate them with depression in lung function tests detected by depletion of diffusing capacity (DLCO). BAL was carried out in 25 untreated, non-smoking patients suffering from diffuse scleroderma and in 12 healthy non-smoking volunteers. For the analysis of lymphocyte sub-sets flow cytometry and monoclonal antibodies were used. The following cell sub-types were counted: T lymphocytes, B lymphocytes, helper lymphocytes, suppressor/cytotoxic lymphocytes, natural killer cells, cytotoxic T lymphocytes and activated T lymphocytes. The total cell count was higher in the group of patients with mild and moderate impairment in DLCO. The percentage of lymphocytes was greater in patients with DLCO lower than 65% of the predicted value since neutrophilia was found in patients with severe DLCO depletion, i.e. significant when compared with healthy subjects. The proportions of suppressor/cytotoxic lymphocytes and of activated T lymphocytes were higher in patients than in controls. The statistical analysis revealed significant differences between patients with moderate and mild changes in DLCO and the healthy volunteers. A decreased helper/suppressor ratio was noticed in these patients. We concluded that the BALF lymphocyte phenotype analysis may reflect the features of alveolitis in patients with SSc.

Induced sputum-retrieved matrix metalloproteinase 9 and tissue metalloproteinase inhibitor 1 in granulomatous diseases

“…We also demonstrated herein a strong inverse correlation between the MMP‐9 and TIMP‐1 levels in IS supernatants with the DLCO capacity in SA patients which show pulmonary involvement and a lesser one in CRD which patients do not show clinical pulmonary manifestations. The role of MMP‐9 in fibrotic diseases of the lung was already shown in many earlier studies [23–38], but we believe this to be the first study to show a correlation between MMP‐9 which is mainly secreted by inflammatory cells and physiological parameters. For this purpose, DLCO proved to be a clinically useful test in the evaluation and follow‐up of diseases which involve lung parenchyma [39].…”

“…These results are in agreement with our previous studies and others [30–32] demonstrating that percentage CD8‐cytotoxic subsets are elevated in BAL fluid from patients with IPF and pulmonary fibrosis‐ associated with systemic sclerosis as well as in collagen vascular disorders. Moreover, this low ratio of CD4/CD8 subtypes due to increase in CD8‐cytotoxic positive cells are associated with DLCO impairment [33]. These results taken together showed that soluble MMP‐9 in correlation to percentage cytotoxic CD8 T lymphocytes in sputum and diffusion capacity may be considered a marker of damage.…”

Cellular interactions in the pathogenesis of interstitial lung diseases

“…A higher number of NK cells has been reported in the BAL and in the blood of patients affected by IPF and SSc [118,119]. Increased levels of several cytokines have been demonstrated in nonstimulated NK cells from SSc patients when compared with controls, suggesting that NK cell dysfunction may contribute to immunological abnormalities in scleroderma.…”

Problems of Cancer Treatment. Part 2. Treatment Based on Modification of Anticancer Immunological Responses in Therapy

“…The cells obtained in BAL can be isolated and cultured. In numerous studies, including our own, significance of BAL was proven in diagnosis of peripheral pulmonary tumours both in the range of cell analysis and produced by them cytokines [7,11,13,14]. A study conducted at present by the authors points to a distinct character of inflammatory reaction in the lung, which contains the tumour than in the lung containing no tumour.…”