Tumour necrosis factor-alpha gene expression by alveolar macrophages in human lung allograft recipient with recurrence of sarcoidosis. Toulouse Lung Transplantation Group

Abstract

T Tu um mo ou ur r n ne ec cr ro os si is s f fa ac ct to or r--α g ge en ne e e ex xp pr re es ss si io on n b by y a al lv ve eo ol la ar r m ma ac cr ro op ph ha ag ge es s i in n h hu um ma an n l lu un ng g a al ll lo og gr ra af ft t r re ec ci ip pi ie en nt t w wi it th h r re ec cu ur rr re en nc ce e o of f s sa ar rc co oi id do os si is s ABSTRACT: Recurrence of sarcoidosis in lung allografts is an interesting model to study the pathogenesis of this disease. We report a case of sarcoidosis recurrence in a single lung allograft recipient 2 years after transplantation. The expression of tumour necrosis factor-α (TNF-α) gene by alveolar macrophages was monitored.The TNF-α gene was not expressed at the time of recurrence of sarcoidosis, but only later when prominent granulomas were observed.

Single-cell analysis: a novel approach to tumour necrosis factor- synthesis and secretion in sarcoidosis

“…The present data are in agreement with other publications on sarcoidosis and TNF [9][10][11][12][13][14][15], although an increase in production in stable disease has been shown here in contrast with previous studies that included patients with active or more progressive disease [22]. It has been shown that AM from patients with sarcoidosis and normal individuals secrete more TNF-a than autologous peripheral blood Mo, but that in sarcoidosis the increased production is due to an increase in the percentage of macrophages secreting TNF-a rather than the average product per cell.…”

“…However, in published data on interleukin (IL)-8 [15] and unpublished observations characterising TNF-a-secreting cells from patients with fibrosing alveolitis (P. Pantelidis), it was confirmed that the majority of these IL-8 and TNFproducing cells bear the RFD 7 phenotype of mature tissue macrophages. This has important implications for targeted management.…”

“…A number of previous publications have demonstrated the upregulation of TNF-a in a variety of contexts including bronchoalveolar lavage (BAL) fluid protein, macrophage protein secretion and macrophage TNF messenger ribonucleic acid content [9][10][11][12][13][14][15][16]. TNF secretion has largely been associated with active disease.…”

Recurrent Sarcoidosis in Lung Transplant Allografts

“…Recurrence of primary disease in lung allografts is well described in the literature although involves a relatively small percentage of patients. [10][11][12][13][14][15][16][17][18] In most cases, recurrence is diagnosed histologically as an incidental finding of noncaseating granulomas on transbronchial lung biopsy and is unrelated to clinical or radiologic abnormalities. 36 A higher than expected rate of rejection also appear to accompany recurrent sarcoidosis in pulmonary allografts.…”

Lung Transplantation for Pulmonary Sarcoidosis

“…In some cases however there may be evidence of graft dysfunction with the onset of respiratory symptoms, and in these patients there is a greater likelihood that there are coexisting infiltrates on radiological investigations (Judson 1998). Recurrence can occur at any stage post transplantation documented from as early as 2 weeks out to 2 years (Johnson, Duncan et al 1993;Martel, Carre et al 1996). Some have suggested that rejection and Sarcoidosis may utilise a common pathway via the activation of Tlymphocytes however, the weight of evidence is against this.…”