Biologic Therapies for Giant Cell Arteritis

Harrington, Robert D.; Nokhatha, Shamma Ahmad Al; Conway, Richard

doi:10.2147/btt.s229662

Cited by 8 publications

(6 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, in experimental autoimmune encephalomyelitis increased expression of PKM2 was found to be a regulator of Th17 cells differentiation and inflammation by interaction with STAT3 enhancing its activity [ 40 ]. Previous studies demonstrated that the JAK-STAT pathway in GCA contributes to the disease’s pathogenesis, and blockade of this pathway was shown to be beneficial in GCA treatment [ 41–43 ]. Here, we first showed a clear increase in expression of PKM2 in inflamed TABs of GCA patients compared with non-GCA patients.…”

Section: Discussionmentioning

confidence: 99%

Plasma Pyruvate Kinase M2 as a marker of vascular inflammation in giant cell arteritis

Esen¹,

Jiemy²,

Sleen³

et al. 2021

Rheumatology

View full text Add to dashboard Cite

Objectives GCA is a large vessel vasculitis in which metabolically active immune cells play an important role. GCA diagnosis is based on CRP/ESR and temporal artery biopsies (TABs), in combination with 18F-fluorodeoxyglucose ([18F]FDG)-PET/CT relying on enhanced glucose uptake by glycolytic macrophages. Here, we studied circulating Pyruvate Kinase M2 (PKM2), a glycolytic enzyme, as a possible systemic marker of vessel wall inflammation in GCA. Methods Immunohistochemical detection of PKM2 was performed on inflamed (n = 12) and non-inflamed (n = 4) TABs from GCA patients and non-GCA (n = 9) patients. Dimeric PKM2 levels were assessed in plasma of GCA patients (n = 44), age-matched healthy controls (n = 41), metastatic melanoma patients (n = 7) and infection controls (n = 11). CRP, ESR and macrophage markers calprotectin and YKL-40 were correlated with plasma PKM2 levels. To detect the cellular source of plasma PKM2 in tissue, double IF staining was performed on inflamed GCA TABs. [18F]FDG-PET scans of 23 GCA patients were analysed and maximum standard uptake values and target to background ratios were calculated. Results PKM2 is abundantly expressed in TABs of GCA patients. Dimeric PKM2 plasma levels were elevated in GCA and correlated with CRP, ESR, calprotectin and YKL-40 levels. Elevated plasma PKM2 levels were downmodulated by glucocorticoid treatment. PKM2 was detected in both macrophages and T cells at the site of vascular inflammation. Circulating PKM2 levels correlated with average target to background ratios PET scores. Conclusion Elevated plasma PKM2 levels reflect active vessel inflammation in GCA and may assist in disease diagnosis and in disease monitoring.

show abstract

Section: Discussionmentioning

confidence: 99%

Plasma Pyruvate Kinase M2 as a marker of vascular inflammation in giant cell arteritis

Esen¹,

Jiemy²,

Sleen³

et al. 2021

Rheumatology

View full text Add to dashboard Cite

show abstract

“…The current hypothesis on the pathogenesis of GCA invokes collaboration between the innate and adaptive immune systems and different compartments of the vessel wall, including endothelial cells (ECs), and vascular smooth muscle cells (VSMCs) [ 14 , 17 , 20 ] ( Figure 1 ). Histologically, GCA is characterized by a pathological granulomatous inflammatory infiltrate within the vessel wall [ 21 , 22 ].…”

Section: Pathophysiology Of Giant Cell Arteritismentioning

confidence: 99%

Advances in the Treatment of Giant Cell Arteritis

Castañeda

Prieto-Peña

Vicente-Rabaneda

et al. 2022

JCM

View full text Add to dashboard Cite

Giant cell arteritis (GCA) is the most common vasculitis among elderly people. The clinical spectrum of the disease is heterogeneous, with a classic/cranial phenotype, and another extracranial or large vessel phenotype as the two more characteristic patterns. Permanent visual loss is the main short-term complication. Glucocorticoids (GC) remain the cornerstone of treatment. However, the percentage of relapses with GC alone is high, and the rate of adverse events affects more than 80% of patients, so it is necessary to have alternative therapeutic options, especially in patients with worse prognostic factors or high comorbidity. MTX is the only DMARD that has shown to reduce the cumulative dose of GC, while tocilizumab is the first biologic agent approved due to its ability to decrease the relapse rate and lower the cumulative GC doses. However, apart from the IL-6 pathway, there are other pro-inflammatory cytokines and growth factors involved in the typical intima hyperplasia and vascular remodeling of GCA. Among them, the more promising targets in GCA treatment are the IL12/IL23 axis antagonists, IL17 inhibitors, modulators of T lymphocytes, and inhibitors of either the JAK/STAT pathway, the granulocyte-macrophage colony-stimulating factor, or the endothelin, all of which are updated in this review.

show abstract

“…This finding excludes the possibility that the symptoms were paraneoplastic. If the patient's symptoms would rapidly progress, we would consider changing the therapy to biological therapy, e.g., interleukin-6 inhibitors (tocilizumab) (18). PTC, the most common thyroid malignancy, is associated with an excellent prognosis.…”

Section: Discussionmentioning

confidence: 99%

Association of Giant Cell Arteritis with Papillary Thyroid Carcinoma

Šípová

Havlínová

Bělobrádková

et al. 2022

Acta Med. (Hradec Kralove, Czech Repub.)

View full text Add to dashboard Cite

Previous studies suggest that there may be an association between cancer and autoimmune diseases. We describe the case of a 59-year-old patient who did not have any significant diseases in the last year. She had new onset of fever of unknown aetiology, headache, fatigue and night sweats. We used laboratory methods to rule out infectious diseases. Significant laboratory findings reported increased signs of inflammation and anti-nuclear antibody (ANA) positivity. Positron emission tomography/computed tomography (PET/CT) imaging showed the origin of the patient’s difficulties, arteritis, with increased metabolic activity in the aortic wall and other arteries. Doppler ultrasonography of the arteries did not show pathology in the temporal arteries but found accelerated blood flow in the superior mesenteric artery (AMS). Another finding from PET/CT was a tumour in the thyroid gland, later verified histologically as papillary thyroid carcinoma (PTC). We investigated the link between rheumatological disease and papillary carcinoma, applying similar therapy, corticosteroids and immunosuppressants.

show abstract

Biologic Therapies for Giant Cell Arteritis

Cited by 8 publications

References 68 publications

Plasma Pyruvate Kinase M2 as a marker of vascular inflammation in giant cell arteritis

Plasma Pyruvate Kinase M2 as a marker of vascular inflammation in giant cell arteritis

Advances in the Treatment of Giant Cell Arteritis

Association of Giant Cell Arteritis with Papillary Thyroid Carcinoma

Contact Info

Product

Resources

About