Mean fold change in mRNA of selected representative genes related to T helper functional differentiation, inflammation and vascular remodelling in cultured temporal arteries from 34 patients with GCA and 21 controls subjected to different treatments (control IgG1, A6, recombinant IFNγ or dexamethasone)
| GCA/control | GCA biopsies | |||
|---|---|---|---|---|
| Fold increase | Clone A6/IgG1 | IFNγ/untreated | Dexa/untreated | |
| Transcription factors | ||||
| TBX21 | 3.1154* | 0.7133 | 2.7776* | 0.9522 |
| GATA3 | 1.7611* | 1.1780 | 1.3536 | 0.7716 |
| RORC | 3.6482* | 0.8558 | 1.3571 | 0.8380* |
| STAT-3 | 0.5913 | 0.9232 | 1.6143 | 1.0565 |
| Proinflammatory molecules | ||||
| Cytokines | ||||
| IL-1β | 3.6162* | 0.9041 | 1.1481 | 0.0342 |
| TNFα | 1.6621* | 0.7561* | 2.7333* | 0.3047* |
| IL-6 | 1.4685 | 0.7026 | 1.5621 | 0.0757* |
| IFNγ | 15.0840* | 0.9119 | 0.6848 | 0.3869* |
| IL17A | 103.5418* | 1.4793 | 0.5557 | 0.0279* |
| Chemokines | ||||
| CCL2 | 1.6839 | 0.8950 | 1.2292 | 0.3424* |
| CCL3 | 6.3415* | 0.9815 | 0.4381 | 0.2125* |
| CCL4 | 13.9455* | 1.0598 | 0.1611 | 0.2058 |
| CCL5 | 4.8446* | 1.2153 | 1.3709 | 0.6600 |
| CXCL8 | 1.3023 | 0.9805 | 0.9512 | 0.0748* |
| Chemokine receptors | ||||
| CCR2 | 6.9054* | 1.3463 | 2.6116 | 0.5746 |
| CXCR3 | 10.0717* | 0.6640 | 2.1125* | Not done |
| Adhesion molecules | ||||
| ICAM-1 | 1.7275 | 0.8225 | 2.0204 | 0.1137 |
| VCAM-1 | 0.7031 | 0.9611 | 1.6861 | 0.0787 |
| Other | ||||
| HLADRA | 3.8304* | 0.7373 | 3.0312* | 0.8810 |
| NOS-2 | 1.7010 | 0.2443 | 2.7067 | 1.7251 |
| Vascular remodelling-related molecules | ||||
| Growth factors | ||||
| PDGFA | 0.4752* | 0.7690 | 1.6640 | 0.4331 |
| PDGFB | 0.6820 | 0.8081 | 1.0921 | 0.6338 |
| TGFβ | 0.6106* | 1.0119 | 1.2298 | 0.5117 |
| Extracellular matrix proteins | ||||
| FN1 | 0.8757 | 1.0473 | Not done | 2.3182 |
| COL1 | 1.9086 | 0.9953 | Not done | 0.9594 |
| COL3 | 0.9037 | 0.8602 | Not done | 1.0790 |
| Metalloproteases | ||||
| MMP-2 | 0.5738* | 0.9101 | 0.5082 | 0.5827 |
| MMP-9 | 2.3692* | 0.8468 | 0.8204 | 0.0708* |
| MMP inhibitors | ||||
| TIMP1 | 1.8323* | 0.9844 | 1.0956 | 0.3405* |
| TIMP2 | 0.5663* | 0.9815 | 0.9614 | 0.7737 |
Number of specimens analysed: negative biopsies: 21; untreated GCA: 29; GCA treated with A6: 21; GCA treated with IgG1: 18; GCA treated with IFNγ: 9; GCA treated with dexamethasone: 11.
Bold values indicate consistent opposite results achieved by blocking IFNγ with A6 or by adding recombinant IFNγ.
*p<0.05.
Clone A6, anti-human IFNγ monoclonal antibody; GCA, giant cell arteritis; IgG1, isotype-matched control immunoglobulin; ICAM, intracellular adhesion molecule; IFNγ, recombinant interferon γ; MMP, matrix metalloproteinases; PDGF, platelet-derived growth factor.