An expanded population of pathogenic regulatory T cells in giant cell arteritis is abrogated by IL-6 blockade therapy

ObjectivesRandomised-controlled trials have recently proven the efficacy of the interleukin (IL)-6 receptor antagonist tocilizumab (TCZ) in giant cell arteritis (GCA). However, the mechanism of action of IL-6 blockade in this disease is unknown. Moreover, the role of regulatory T (Treg) cells in the pathogenesis of GCA remains underexplored. Given the plasticity of Tregs and the importance of IL-6 in their biology, we hypothesised that TCZ might modulate the Treg response in GCA. We therefore characterised the Treg compartment of patients with GCA treated with TCZ.MethodsWe classified 41 patients with GCA into three groups: active disease (aGCA, n=11), disease remission on corticosteroids (rGCA-CS, n=19) and disease remission on TCZ (rGCA-TCZ, n=11). Healthy controls (HCs) were included for comparison. We determined the frequency, phenotype and function of peripheral blood Tregs.ResultsPatients with aGCA demonstrated a hypoproliferating Treg compartment enriched in IL-17-secreting Tregs (IL-17+Tregs). Tregs in patients with aGCA disproportionally expressed a hypofunctional isoform of Foxp3 that lacks exon 2 (Foxp3Δ2). Foxp3Δ2-expressing Tregs coexpressed CD161, a marker commonly associated with the Th17 linage, significantly more often than full-length Foxp3-expressing Tregs. Compared with those of HCs, GCA-derived Tregs demonstrated impaired suppressor capacity. Treatment with TCZ, in contrast to CS therapy, corrected the Treg abnormalities observed in aGCA. In addition, TCZ treatment increased the numbers of activated Tregs (CD45RA−Foxp3high) and the Treg expression of markers of trafficking (CCR4) and terminal differentiation (CTLA-4).ConclusionsTCZ may exert its therapeutic effects in GCA by increasing the proliferation and activation of Tregs, and by reverting the pathogenic Treg phenotype seen during active disease.

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FRI0212 THE ROLE OF AGE ON THE CLINICAL PRESENTATION AND RELAPSE RATES IN A LARGE COHORT OF 720 PATIENTS WITH GIANT CELL ARTERITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3779 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 689.1-690

Author(s):

S. Monti ◽

L. Dagna ◽

C. Campochiaro ◽

A. Tomelleri ◽

G. Zanframundo ◽

...

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell ◽

Relapse Rate ◽

Clinical Presentation ◽

Age Groups ◽

Age At Diagnosis ◽

First Relapse ◽

Time To Relapse

Background:Giant cell arteritis (GCA) is the most frequent systemic vasculitis after the age of 50 years old. Recent interest in the processes of immune and vascular aging have been proposed as a disease risk factor. Data on the impact of age at diagnosis of GCA on the clinical course of the disease are scarceObjectives:To assess the role of age at diagnosis of GCA on the risk and time to relapseMethods:Centres participating in the Italian Society of Rheumatology Vasculitis Study Group retrospectively enrolled patients with a diagnosis of GCA until December 2019. The cohort was divided in tertiles according to age at diagnosis (≤ 72; 73-79; > 79 years old). Negative binomial regression was used to assess the relapse rate according to age groups, and Cox regression for time to first relapse.Results:Of 720 patients enrolled in 14 Italian reference centres, 711 had complete follow-up data (female 50%; mean age 75±7). Median follow-up duration was 34 months (IQR 16;70). Patients in the older group at diagnosis (> 79 years) had more frequent visual loss compared to the 73-79 and ≤ 72 age groups (31% vs 20% vs 7%; p<0.001), but lower rates of general symptoms (56% vs 70% vs 77%; p<0.001). Large-vessel (LV)-GCA was less frequent in the older group (18% vs 22% vs 43%; p<0.001). At least one relapse occurred in 47% of patients. Median time to relapse was 12 months (IQR 6;23). Age did not influence the rate of relapses [18 per 100 persons/years (95%CI 15;21) vs 19 (95% CI 17;22) vs 19 (95%CI 17;22)], nor the time to first relapse (Figure 1). LV-GCA, presentation with significantly elevated c-reactive protein (> 50 mg/L) and general symptoms were independent predictors of relapse.Conclusion:Age at diagnosis of GCA influenced the clinical presentation and risk of ischaemic complications, but did not affect the relapse rate during follow-up. LV-GCA occurred more frequently in younger patients and was an independent predictor of relapse risk, highlighting the need for a correct characterization of the clinical subtype at the early stages of disease.Disclosure of Interests:Sara Monti: None declared, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Alessandro Tomelleri: None declared, Giovanni Zanframundo: None declared, Catherine Klersy: None declared, Francesco Muratore: None declared, Luigi Boiardi: None declared, Roberto Padoan: None declared, Mara Felicetti: None declared, Franco Schiavon: None declared, Milena Bond: None declared, Alvise Berti: None declared, Roberto Bortolotti: None declared, Carlotta Nannini: None declared, Fabrizio Cantini: None declared, Alessandro Giollo: None declared, Edoardo Conticini: None declared, angelica gattamelata: None declared, Roberta Priori: None declared, Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Elena Treppo: None declared, Giacomo Emmi: None declared, Martina Finocchi: None declared, Giulia Cassone: None declared, Ariela Hoxha Speakers bureau: Celgene, UCB, Novartis, Sanofi, Werfen, Rosario Foti Consultant of: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Speakers bureau: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Michele Colaci: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Carlo Salvarani: None declared, Carlomaurizio Montecucco: None declared

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The role of temporal artery biopsies in giant cell arteritis

Annals of The Royal College of Surgeons of England ◽

10.1308/003588411x12851639107476 ◽

2011 ◽

Vol 93 (1) ◽

pp. 4-5 ◽

Cited By ~ 21

Author(s):

CG Davies ◽

DJ May

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell ◽

No Value ◽

Disease Process ◽

Temporal Artery

A knowledge of the disease process of giant cell arteritis and its diagnosis can help a surgeon to decide which patients will benefit from a biopsy being performed and identify where a biopsy would be of no value in their management. This article discusses the issues involved.

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Role of the CCR5/Δ32CCR5 polymorphism in biopsy-proven giant cell arteritis

Human Immunology ◽

10.1016/j.humimm.2011.02.009 ◽

2011 ◽

Vol 72 (5) ◽

pp. 458-461 ◽

Cited By ~ 8

Author(s):

F. David Carmona ◽

Luis Rodríguez-Rodríguez ◽

Santos Castañeda ◽

José A. Miranda-Filloy ◽

Inmaculada C. Morado ◽

...

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell

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Role of rs1343151 IL23R and rs3790567 IL12RB2 Polymorphisms in Biopsy-proven Giant Cell Arteritis

The Journal of Rheumatology ◽

10.3899/jrheum.101046 ◽

2011 ◽

Vol 38 (5) ◽

pp. 889-892 ◽

Cited By ~ 15

Author(s):

LUIS RODRÍGUEZ-RODRÍGUEZ ◽

FRANCISCO D. CARMONA ◽

SANTOS CASTAÑEDA ◽

JOSÉ A. MIRANDA-FILLOY ◽

INMACULADA C. MORADO ◽

...

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell ◽

Polymerase Chain Reaction Amplification ◽

Phenotypic Expression ◽

Minor Allele ◽

Potential Association ◽

Ischemic Complications ◽

Reaction Amplification ◽

Polymerase Chain

Objective.To assess the potential association between the rs1343151 IL23R and the rs3790567 IL12RB2 polymorphisms and giant cell arteritis (GCA). We also studied whether these polymorphisms might influence the phenotypic expression of GCA.Methods.In total, 357 Spanish patients with biopsy-proven GCA and 574 matched controls were assessed. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for the rs1343151 IL23R and the rs3790567 IL12RB2 polymorphisms using a predesigned TaqMan allele discrimination assay and by polymerase chain reaction amplification.Results.Regarding the rs1343151 IL23R polymorphism, no significant differences in the genotype or allele frequencies between GCA patients and healthy controls were observed. The frequency of the minor allele A of the rs3790567 IL12RB2 variant was increased in GCA patients compared with controls (30.1% vs 25.7%, respectively; p = 0.039, OR 1.25, 95% CI 1.01–1.54). An increased frequency of subjects carrying the minor allele A (GA+AA genotypes) of the rs3790567 IL12RB2 polymorphism was found among GCA patients compared with controls (52.8% vs 44.4%; p = 0.013, OR 1.40, 95% CI 1.06–1.85). Although a higher frequency of the combination of minor alleles (A-A) in the subgroup of patients with visual ischemic complications compared with the combination of both major alleles (G-G; p = 0.029) or with the other allelic combinations (p = 0.035) was found, logistic regression analysis showed that this association was no longer significant after adjustment for potential confounding factors (A-A vs G-G: OR 2.10, 95% CI 0.88–5.04, p = 0.096).Conclusion.Our results support a potential influence of the rs3790567 IL12RB2 polymorphism in the pathogenesis of GCA.

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Giant cell arteritis mimicking fever of unknown origin: potential diagnostic role of PET scan

Thrombosis and Haemostasis ◽

10.1055/s-0037-1612651 ◽

2006 ◽

Vol 95 (02) ◽

pp. 390-392 ◽

Cited By ~ 1

Author(s):

Olivier Chavaillaz ◽

Salah Gueddi ◽

Sophia Taylor ◽

Hans Stalder ◽

Marc Righini

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell ◽

Fever Of Unknown Origin ◽

Unknown Origin ◽

Pet Scan ◽

Diagnostic Role

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The role of vascular ultrasound in managing giant cell arteritis in ophthalmology

Survey of Ophthalmology ◽

10.1016/j.survophthal.2019.11.004 ◽

2020 ◽

Vol 65 (2) ◽

pp. 218-226

Author(s):

Jared Ching ◽

Sonja Mansfield Smith ◽

Bhaskar Dasgupta ◽

Erika Marie Damato

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell ◽

Vascular Ultrasound

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Lack of Association Between STAT4 Gene Polymorphism and Biopsy-proven Giant Cell Arteritis

The Journal of Rheumatology ◽

10.3899/jrheum.081060 ◽

2009 ◽

Vol 36 (5) ◽

pp. 1021-1025 ◽

Cited By ~ 7

Author(s):

ROGELIO PALOMINO-MORALES ◽

TOMAS R. VAZQUEZ-RODRIGUEZ ◽

INMACULADA C. MORADO ◽

SANTOS CASTAÑEDA ◽

NORBERTO ORTEGO-CENTENO ◽

...

Keyword(s):

Gene Polymorphism ◽

Giant Cell Arteritis ◽

Giant Cell ◽

Statistical Significance ◽

Clinical Manifestations ◽

Clinical Expression ◽

Potential Implication ◽

Genotype Frequencies ◽

Ischemic Complications

Objective.To investigate the potential implication of the STAT4 gene polymorphism rs7574865 in the predisposition to or the clinical expression of giant cell arteritis (GCA).Methods.A total of 212 patients diagnosed with biopsy-proven GCA were studied. DNA from patients and controls matched by age, sex, and ethnicity was obtained from peripheral blood. Samples were genotyped for STAT4 rs7574865 polymorphism.Results.No statistically significant differences in the allele frequencies for the STAT4 rs7574865 polymorphism were observed between patients and controls. Although we observed an increased frequency of the T/T genotype in GCA patients (6.0%) compared to healthy controls (3.9%), this difference did not achieve statistical significance (OR 1.57, 95% CI 0.72–3.41). No statistically significant differences in allele or genotype frequencies were observed when patients were stratified according to the presence of typical disease features such as polymyalgia rheumatica, severe ischemic manifestations, and visual ischemic complications in the setting of this vasculitis.Conclusion.Our results do not support a major role of the STAT4 rs7574865 gene polymorphism in susceptibility to or clinical manifestations of GCA.

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