Rationale: Sarcoidosis is a multisystem disease of unknown cause. Löfgren’s syndrome (LS) is a characteristic subgroup of sarcoidosis that is associated with a good prognosis in sarcoidosis. However, little is known about its genetic architecture or its broader phenotype, non-LS sarcoidosis. Objectives: To address the genetic architecture of sarcoidosis phenotypes, LS and non-LS. Methods: An association study in a white Swedish cohort of 384 LS, 664 non-LS, and 2,086 control subjects, totaling 3,134 subjects using a fine-mapping genotyping platform was conducted. Replication was performed in four independent cohorts, three of white European descent (Germany, n = 4,975; the Netherlands, n = 613; and Czech Republic, n = 521), and one of black African descent (United States, n = 1,657), totaling 7,766 subjects. Measurements and Main Results: A total of 727 LS-associated variants expanding throughout the extended major histocompatibility complex (MHC) region and 68 non-LS–associated variants located in the MHC class II region were identified and confirmed. A shared overlap between LS and non-LS defined by 17 variants located in the MHC class II region was found. Outside the MHC region, two LS-associated loci, in ADCY3 and between CSMD1 and MCPH1, were observed and replicated. Conclusions: Comprehensive and integrative analyses of genetics, transcription, and pathway modeling on LS and non-LS indicates that these sarcoidosis phenotypes have different genetic susceptibility, genomic distributions, and cellular activities, suggesting distinct molecular mechanisms in pathways related to immune response with a common region.

Chronic obstructive pulmonary disease (COPD) is characterised by irreversible airflow limitation associated with chronic inflammation. Matrix metalloproteinases (MMPs) are proteolytic enzymes that contribute to the inflammatory response in COPD and degrade extracellular matrix components. Their enzymatic activity is inhibited by a four-member family of tissue inhibitors of metalloproteinases (TIMPs). In COPD, the MMP/TIMP network, mainly MMP-9, has been repeatedly observed to be dysregulated at both the local (lung) and systemic levels. Here, we review the findings reported in numerous cross-sectional studies with our primary focus on longitudinal observations in human COPD studies. The data from longitudinal prospective studies on the MMP/TIMP network may lead to the introduction of novel prognostic biomarkers into clinical management of COPD. We address the relationship between the systemic and local lung MMP/TIMP network in COPD patients and briefly describe the involvement of microRNAs. Finally, the role of the MMP/TIMP network in COPD treatment is discussed.

Background: Chemokines and chemokine receptors are major mediators of leukocyte trafficking into the sites of the immune response. They participate in defence against microbial infection, in Th1/Th2 polarization of the immune response, allogra...

For accuracy of quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), normalisation with suitable reference genes is required. To date, no reference genes have been validated for expression studies of bronchoalveolar (BAL) cells. The aims of this study were to identify gene(s) with stable mRNA expression in BAL cells irrespective of gender, smoking, BAL cellular composition, lung pathology, treatment; and to assess the influence of reference genes on target gene expression data.

Purpose. Pulmonary sarcoidosis is associated with dysregulated expression of intracellular miRNAs. There is however only little information on extracellular miRNAs and their association with the disease course in sarcoidosis. We therefore assessed serum miRNAs in sarcoidosis classified according to the presence of Löfgren’s syndrome (LS) as a hallmark of good prognosis in contrast to more advanced disease course.Methods. RT-PCR was used to assess 35 miRNAs in 13 healthy controls and 24 sarcoidosis patients (12 with X-ray (CXR) stage≤1 and LS and 12 with insidious onset and CXR stage≥3).Results. Compared to controls, we consistently observed dysregulated expressions of miR-146, miR-16, miR-425-5p, and miR-93-5p in both sarcoidosis groups irrespective of disease course. Specifically, patients without LS had dysregulated expressions of miR-150-5p, miR-1, and miR-212 compared to controls. Patients with LS had dysregulated expressions of miR-21-5p and miR-340-5p compared to controls. Bioinformatics predicted consistently “Pathways in cancer” to be modulated by both altered profiles in patients with/without LS. Three miRNAs (miR-21-5p, miR-340-5p, and miR-212-3p) differed between our patients with LS and those without LS; their cumulative effect may modulate “TGF-βsignalling pathway.”Conclusions. Further study should focus on possible applications of serum miRNAs for diagnostics follow-up and for prognosis.