Sarcoidosis: TNF- α Release from Alveolar Macrophages and Serum Level of sIL-2R Are Prognostic Markers

Ziegenhagen, Manfred W.; Benner, U.; Zissel, Gernot; Zabel, P.; Schlaak, M; Müller–Quernheim, Joachim

doi:10.1164/ajrccm.156.5.97-02050

Cited by 217 publications

(165 citation statements)

References 30 publications

Supporting

Mentioning

141

Contrasting

Unclassified

Order By: Relevance

“…However, our results suggest that additional biological signals aside from IFN contribute to disease severity and progression. Some studies have suggested higher TNF signalling predicts disease progression [30,31].…”

Section: Discussionmentioning

confidence: 99%

Longitudinal analysis of sarcoidosis blood transcriptomic signatures and disease outcomes

Su¹,

Li²,

Bhakta³

et al. 2014

Eur Respir J

View full text Add to dashboard Cite

Previously, we demonstrated concordance in differentially expressed genes in sarcoidosis blood and lung, implicating shared dysfunction of specific immune pathways. In the present study, we hypothesised that expression levels of candidate genes in sarcoidosis blood could predict and track with disease outcomes longitudinally.We applied Ingenuity Pathway Analysis to a cross-sectional derivation microarray dataset (n538) to identify canonical pathways and candidate genes associated with sarcoidosis. In a separate longitudinal sarcoidosis cohort (n5103), we serially measured 48 candidate gene transcripts, and assessed their relation to disease chronicity and severity.In the cross-sectional derivation study, pathway analysis showed upregulation of genes related to interferon signalling and the role of pattern recognition receptors, and downregulation of T-cell receptor (TCR) signalling pathways in sarcoidosis. In the longitudinal cohort, factor analysis confirmed coregulation of genes marking these pathways and identified CXCL9 as an additional candidate pathway. CXCL9 and TCR factors discriminated between chronic versus nonprogressive disease, and CXCL9 predicted disease outcomes longitudinally. Interferon factor was similarly increased in both disease phenotypes. Factors associated with lung function decline included decreased TCR factor and increased CXCL9.These findings demonstrate blood transcriptomic signatures reflecting TCR signalling and CXCL9 predict sarcoidosis chronicity and correlate with disease severity longitudinally. @ERSpublications Blood gene transcript measurements predict sarcoidosis chronicity and severity longitudinally

show abstract

Section: Discussionmentioning

confidence: 99%

Longitudinal analysis of sarcoidosis blood transcriptomic signatures and disease outcomes

Su¹,

Li²,

Bhakta³

et al. 2014

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…Although the potential pathogenic role of excess TNF-a in granulomatous disease [9,[15][16][17][18] is well documented, TNF-a does not solely account for the T-helper cell type 1 (Th-1) dominated cytokine environment in the sarcoid lung; in particular, high levels of interferon (IFN)-c have also been implicated in the pathogenesis of sarcoidosis [19]. In addition, alveolar macrophages from patients with sarcoidosis have been shown to produce interleukin (IL)-12 in addition to TNF-a, IL-1b, and IL-6 [20][21][22][23][24][25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of ustekinumab or golimumab in patients with chronic sarcoidosis

et al. 2014

View full text Add to dashboard Cite

Sarcoidosis is characterised by non-caseating granulomas that secrete pro-inflammatory cytokines, including interleukin (IL)-12, IL-23, and tumour necrosis factor (TNF)-a. Ustekinumab and golimumab are monoclonal antibodies that specifically inhibit IL-12/IL-23 and TNF-a, respectively.Patients with chronic pulmonary sarcoidosis (lung group) and/or skin sarcoidosis (skin group) received either 180 mg ustekinumab at week 0 followed by 90 mg every 8 weeks, 200 mg golimumab at week 0 followed by 100 mg every 4 weeks, or placebo. Patients underwent corticosteroid tapering between weeks 16 and 28. The primary end-point was week 16 change in percentage predicted forced vital capacity (DFVC % pred) in the lung group. Major secondary end-points were: week 28 for DFVC % pred, 6-min walking distance, St George's Respiratory Questionnaire (lung group), and Skin Physician Global Assessment response (skin group).At week 16, no significant differences were observed in DFVC % pred with ustekinumab (-0.15, p50.13) or golimumab (1.15, p50.54) compared with placebo (2.02). At week 28, there were no significant improvements in the major secondary end-points, although a nonsignificant numerically greater Skin Physician Global Assessment response was observed following golimumab treatment (53%) when compared with the placebo (30%). Serious adverse events were similar in all treatment groups.Although treatment was well tolerated, neither ustekinumab nor golimumab demonstrated efficacy in pulmonary sarcoidosis. However, trends towards improvement were observed with golimumab in some dermatological end-points. @ERSpublicationsNeither ustekinumab nor golimumab demonstrated efficacy for the treatment of patients with pulmonary sarcoidosis

show abstract

“…Since the 1980s, several studies analysing the role of the percentage of BALF lymphocytes and the CD4/CD8 ratio have been performed with diverse results [4][5][6][7]. Since the late 1990s, however, there has been increasing evidence that neutrophilic alveolitis may play an important role in the outcome of sarcoidosis.…”

mentioning

confidence: 99%

Bronchoalveolar and serological parameters reflecting the severity of sarcoidosis

Ziegenhagen

Rothe²,

Schlaak³

et al. 2003

Eur Respir J

186

129

View full text Add to dashboard Cite

The aim of the present study was to determine which bronchoalveolar lavage fluid (BALF) and serological parameters reflect the severity of newly diagnosed pulmonary sarcoidosis.Seventy-four previously untreated sarcoid patients were categorised into three groups: 10 patients with Löfgren9s syndrome, 51 patients with stable disease and 13 patients with progressing disease requiring systemic steroid treatment.Total BALF cell count, percentage of alveolar lymphocytes and lymphocyte CD4/ CD8 ratio were not associated with severity of disease. Interestingly, a significant increase in percentages of BALF neutrophils (5.2¡1.1%) and eosinophils (1.7¡0.6%) was observed in sarcoid patients with progressing disease. Elevated percentages of these two cell types were the only BALF parameters associated with a more frequent necessity for systemic steroid therapy. This association between an elevated percentage of BALF neutrophils and the necessity for steroid treatment was observed in advanced as well as early sarcoidosis (radiological types I and II). Serum levels of soluble interleukin-2 receptor and neopterin were significantly elevated in progressing disease compared to stable disease or Löfgren9s syndrome.The present results demonstrate that increased percentages of neutrophils (w3.0%) and eosinophils (w1%) in bronchoalveolar lavage fluid from newly diagnosed pulmonary sarcoidosis is associated with a significantly higher risk of necessity for steroid therapy and may be helpful markers of progressive disease. Furthermore, of the serological parameters investigated, only serum levels of soluble interleukin-2 receptor and neopterin were associated with disease severity. Eur Respir J 2003; 21: 407-413.

show abstract

Sarcoidosis: TNF- α Release from Alveolar Macrophages and Serum Level of sIL-2R Are Prognostic Markers

Cited by 217 publications

References 30 publications

Longitudinal analysis of sarcoidosis blood transcriptomic signatures and disease outcomes

Longitudinal analysis of sarcoidosis blood transcriptomic signatures and disease outcomes

Safety and efficacy of ustekinumab or golimumab in patients with chronic sarcoidosis

Bronchoalveolar and serological parameters reflecting the severity of sarcoidosis

Contact Info

Product

Resources

About