RGD Reference Report - Interferon and alternative activation of monocyte/macrophages in systemic sclerosis-associated pulmonary arterial hypertension. - Rat Genome Database

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Interferon and alternative activation of monocyte/macrophages in systemic sclerosis-associated pulmonary arterial hypertension.

Authors: Christmann, RB  Hayes, E  Pendergrass, S  Padilla, C  Farina, G  Affandi, AJ  Whitfield, ML  Farber, HW  Lafyatis, R 
Citation: Christmann RB, etal., Arthritis Rheum. 2011 Jun;63(6):1718-28. doi: 10.1002/art.30318.
RGD ID: 8549528
Pubmed: PMID:21425123   (View Abstract at PubMed)
PMCID: PMC4030759   (View Article at PubMed Central)
DOI: DOI:10.1002/art.30318   (Journal Full-text)

OBJECTIVE: To explore the relationship between biomarkers of pulmonary arterial hypertension (PAH), interferon (IFN)-regulated gene expression, and the alternative activation pathway in systemic sclerosis (SSc). METHODS: Peripheral blood mononuclear cells (PBMCs) were purified from healthy controls, patients with idiopathic PAH, and SSc patients (classified as having diffuse cutaneous SSc, limited cutaneous SSc [lcSSc] without PAH, and lcSSc with PAH). IFN-regulated and "PAH biomarker" genes were compared after supervised hierarchical clustering. Messenger RNA levels of selected IFN-regulated genes (Siglec1 and MX1), biomarker genes (IL13RA1, CCR1, and JAK2), and the alternative activation marker gene (MRC1) were analyzed on PBMCs and on CD14- and CD14+ cell populations. Interleukin-13 (IL-13) and IL-4 concentrations were measured in plasma by immunoassay. CD14, MRC1, and IL13RA1 surface expression was analyzed by flow cytometry. RESULTS: Increased PBMC expression of both IFN-regulated and biomarker genes distinguished SSc patients from healthy controls. Expression of genes in the biomarker cluster, but not in the IFN-regulated cluster, distinguished lcSSc with PAH from lcSSc without PAH. The genes CCR1 (P<0.001) and JAK2 (P<0.001) were expressed more highly in lcSSc patients with PAH compared with controls and mainly by CD14+ cells. MRC1 expression was increased exclusively in lcSSc patients with PAH (P<0.001) and correlated strongly with pulmonary artery pressure (r=0.52, P=0.03) and higher mortality (P=0.02). MRC1 expression was higher in CD14+ cells and was greatly increased by stimulation with IL-13. IL-13 concentrations in plasma were most highly increased in lcSSc patients with PAH (P<0.001). CONCLUSION: IFN-regulated and biomarker genes represent distinct, although related, clusters in lcSSc patients with PAH. MRC1, a marker for the effect of IL-13 on alternative monocyte/macrophage activation, is associated with this severe complication and is related to mortality.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pulmonary hypertension  IEP 8549528associated with Scleroderma more ...RGD 
pulmonary hypertension  ISOIL13 (Homo sapiens)8549528; 8549528associated with Scleroderma more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il13  (interleukin 13)

Genes (Mus musculus)
Il13  (interleukin 13)

Genes (Homo sapiens)
IL13  (interleukin 13)


Additional Information