Association between the<i>FCGR3A</i>V158F polymorphism and the clinical response to infliximab in rheumatoid arthritis and spondyloarthritis patients

Morales-Lara, María José; Conesa‐Zamora, Pablo; García-Simón, María Sergia; Pedrero, F; Santaclara, V; Pérez‐Guillermo, Miguel; Soriano-Navarro, Eduardo

doi:10.3109/03009741003781969

Cited by 31 publications

(28 citation statements)

References 10 publications

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“…Together with the results of other studies on PsA, AS, and CD 17,20 , this stands in contrast to the results in RA, where 3 out of 4 published studies have found a better response in patients homozygous for low-affinity FCGR3A (FF) alleles 9,10,17,21 . In our previous study on RA, which had a similar sample size to our present study, low-affinity FCGR3A and FCGR2A alleles were associated with a better response to infliximab therapy 9 .…”

Section: Rheumatologycontrasting

confidence: 67%

“…Fifty-four percent of patients were male, with a median age at inclusion of 49 (IQR 41, 59) years, disease duration 12 (IQR 8,17) A total of 81.6% of patients had a peripheral arthritis pattern (30% oligoarthritis, ≤ 4 inflamed joints; and 51.6% polyarthritis, > 4 inflamed joints) without axial inflammation, and 18.4% had a mixed pattern (peripheral arthritis plus axial disease defined by radiological sacroiliitis and inflammatory back pain). The PGA score at inclusion was 23% clear, 20% minimal, 32% mild, 19% moderate, and 6% severe psoriasis.…”

Section: Resultsmentioning

confidence: 99%

“…To our knowledge, no previous studies have analyzed the association between the FCGR2A polymorphism and the response to TNF-α blocker in patients with PsA, and there is only 1 limited study on the FCGR3A polymorphism 17 . That study analyzed the specific distribution of the FCGR3A V158F polymorphism in relation to infliximab response at 3, 6, and 12 months in 16 patients with PsA, and found that more patients with a high-affinity genotype (FV+VV) reached a EULAR response at 3 months (20% FF vs 83.3% FV-VV; p = 0.036, Fisher's test p = 0.067) 17 .…”

Section: Discussionmentioning

confidence: 99%

“…That study analyzed the specific distribution of the FCGR3A V158F polymorphism in relation to infliximab response at 3, 6, and 12 months in 16 patients with PsA, and found that more patients with a high-affinity genotype (FV+VV) reached a EULAR response at 3 months (20% FF vs 83.3% FV-VV; p = 0.036, Fisher's test p = 0.067) 17 . Similarly, a significant association was observed between the high-affinity V allele and better response in 33 patients with ankylosing spondylitis (AS) at 6 months in terms of both genotype and allele distributions (33.3% FF vs 84.6% FV-VV; p = 0.008; and 45.4% F vs 88.2% V; p = 0.003, respectively) 17 . In accord with these results, the rs767455 polymorphism in TNFR1A seems to have opposite effects on the response to TNF-α blockers in PsA and RA (Conesa-Zamora P, personal communication).…”

Section: Discussionmentioning

confidence: 99%

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FCGR2A/CD32AandFCGR3A/CD16AVariants and EULAR Response to Tumor Necrosis Factor-α Blockers in Psoriatic Arthritis: A Longitudinal Study with 6 Months of Followup

Ramírez¹,

Fernández-Sueiro²,

López‐Mejías³

et al. 2012

J Rheumatol

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Objective.The efficacy of antibody-based biological therapies currently used in psoriatic arthritis (PsA) depends not only on their blocking effect on the targeted molecule but also on their binding affinity to genetically defined variants of cell-surface Fc-γ receptors. Our objective was to assess the potential influence of functionally relevantFCGR2A/CD32A(H131R) andFCGR3A/CD16A(V158F) genetic polymorphisms on the EULAR response to tumor necrosis factor-α (TNF-α) blocker therapy in PsA.Methods.In total 103 patients with PsA starting anti-TNF-α therapy were included. The efficacy of therapy was evaluated according to EULAR response criteria at 3 and 6 months.FCGR2A-R131H andFCGR3A-F158V polymorphisms were genotyped. Potential correlations between clinical response and theFCGR2A-R131H andFCGR3A-F158V polymorphisms were evaluated.Results.EULAR response (moderate plus good) was 85.4% at 3 months and 87.4% at 6 months, while good EULAR response was 61.2% and 62.1%, respectively. More patients with high-affinityFCGR2Agenotypes (homozygous or heterozygous combinations) achieved a EULAR response at 6 months compared to patients with the low-affinity genotype (RR; p = 0.034, adjusted comparison error rate < 0.025). This association was due mainly to the group of patients treated with etanercept. No correlation was found for theFCGR3Apolymorphism. Similarly, no effect of C-reactive protein levels was observed.Conclusion.Our data indicate thatFCGR2Apolymorphism may influence the response to TNF-α blockers (namely etanercept) in PsA in a direction opposite to that previously found in patients with rheumatoid arthritis.

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Section: Rheumatologycontrasting

confidence: 67%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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FCGR2A/CD32AandFCGR3A/CD16AVariants and EULAR Response to Tumor Necrosis Factor-α Blockers in Psoriatic Arthritis: A Longitudinal Study with 6 Months of Followup

Ramírez¹,

Fernández-Sueiro²,

López‐Mejías³

et al. 2012

J Rheumatol

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“…Mice deficient in FcγRIII are protected from the development of collagen induced arthritis without alteration of their humoral response, and therefore the protection is not due to alterations in T-cell responses (Ståhl et al, 2002; Andrén et al, 2006). Polymorphisms in Fcγ receptors are associated with incidence of RA as well as response to therapy (Morgan et al, 2006; Canete et al, 2009; Thabet et al, 2009; Morales-Lara et al, 2010). …”

Section: Activation Of Synovial Macrophagesmentioning

confidence: 99%

Macrophages in Synovial Inflammation

Kennedy¹,

Fearon²,

Veale³

et al. 2011

Front. Immun.

156

123

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Synovial macrophages are one of the resident cell types in synovial tissue and while they remain relatively quiescent in the healthy joint, they become activated in the inflamed joint and, along with infiltrating monocytes/macrophages, regulate secretion of pro-inflammatory cytokines and enzymes involved in driving the inflammatory response and joint destruction. Synovial macrophages are positioned throughout the sub-lining layer and lining layer at the cartilage–pannus junction and mediate articular destruction. Sub-lining macrophages are now also considered as the most reliable biomarker for disease severity and response to therapy in rheumatoid arthritis (RA). There is a growing understanding of the molecular drivers of inflammation and an appreciation that the resolution of inflammation is an active process rather than a passive return to homeostasis, and this has implications for our understanding of the role of macrophages in inflammation. Macrophage phenotype determines the cytokine secretion profile and tissue destruction capabilities of these cells. Whereas inflammatory synovial macrophages have not yet been classified into one phenotype or another it is widely known that TNFα and IL-l, characteristically released by M1 macrophages, are abundant in RA while IL-10 activity, characteristic of M2 macrophages, is somewhat diminished. Here we will briefly review our current understanding of macrophages and macrophage polarization in RA as well as the elements implicated in controlling polarization, such as cytokines and transcription factors like NFκB, IRFs and NR4A, and pro-resolving factors, such as LXA4 and other lipid mediators which may promote a non-inflammatory, pro-resolving phenotype, and may represent a novel therapeutic paradigm.

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The Role of Fcγ Receptor Polymorphisms in the Response to Anti–Tumor Necrosis Factor Therapy in Psoriasis

et al. 2013

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Association between theFCGR3AV158F polymorphism and the clinical response to infliximab in rheumatoid arthritis and spondyloarthritis patients

Cited by 31 publications

References 10 publications

FCGR2A/CD32AandFCGR3A/CD16AVariants and EULAR Response to Tumor Necrosis Factor-α Blockers in Psoriatic Arthritis: A Longitudinal Study with 6 Months of Followup

FCGR2A/CD32AandFCGR3A/CD16AVariants and EULAR Response to Tumor Necrosis Factor-α Blockers in Psoriatic Arthritis: A Longitudinal Study with 6 Months of Followup

Macrophages in Synovial Inflammation

The Role of Fcγ Receptor Polymorphisms in the Response to Anti–Tumor Necrosis Factor Therapy in Psoriasis

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