A prospective observational cohort study and systematic review of 40 patients with mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome

Luo, Yiming; Bolek, E. C.; Quinn, Kaitlin A.; Wells, Kristina; Rose, Emily; Sikora, Keith A.; Goodspeed, Wendy; Rominger, Emily; Kılıç, Levent; Karadağ, Ömer; Clark, Cindy; Livinski, Alicia A.; Grayson, Peter C.; Ferrada, Marcela

doi:10.1016/j.semarthrit.2021.10.007

Cited by 9 publications

(3 citation statements)

References 30 publications

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“…The role of DCBLD2 ultra-rare damaging variants in the development of RP is unclear. MAGIC syndrome is a subset of RP characterised by overlapping features of Behcet’s disease and higher prevalence of aortitis and Raynaud’s phenomenon 22. Our study observed a numerically higher proportion of clinical features of MAGIC syndrome, including mucosal ulcerations and cardiovascular manifestations, in patients with DCBLD2 ultra-rare damaging QVs, but the sample size in this study was insufficient to definitively conclude whether these ultra-rare variants lead to a distinctive phenotype of RP.…”

Section: Discussioncontrasting

confidence: 52%

“…MAGIC syndrome is a subset of RP characterised by overlapping features of Behcet's disease and higher prevalence of aortitis and Raynaud's phenomenon. 22 Our study observed a numerically higher proportion of clinical features of MAGIC syndrome, including mucosal ulcerations and cardiovascular manifestations, in patients with DCBLD2 Figure 3 Pedigree plot of patients with RP with DCBLD2 ultra-rare damaging QVs and genotype data from family members available. In the five unrelated patients with RP and DCBLD2 ultra-rare damaging QVs, three of them have genotype data of family members available.…”

Section: Discussionmentioning

confidence: 55%

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Ultra-rare genetic variation in relapsing polychondritis: a whole-exome sequencing study

Luo,

Ferrada,

Sikora

et al. 2023

Ann Rheum Dis

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ObjectiveRelapsing polychondritis (RP) is a systemic inflammatory disease of unknown aetiology. The objective of this study was to examine the contribution of rare genetic variations to RP.MethodsWe performed a case–control exome-wide rare variant association analysis that included 66 unrelated European American cases with RP and 2923 healthy controls (HC). Gene-level collapsing analysis was performed using Firth’s logistics regression. Exploratory pathway analysis was performed using three different methods: Gene Set Enrichment Analysis, sequence kernel association test and higher criticism test. Plasma DCBLD2 levels were measured in patients with RP and HC using ELISA.ResultsIn the collapsing analysis, RP was associated with a significantly higher burden of ultra-rare damaging variants in theDCBLD2gene (7.6% vs 0.1%, unadjusted OR=79.8, p=2.93×10−7). Plasma DCBLD2 protein levels were significantly higher in RP than in HC (median 4.06 ng/µL vs 0.05 ng/µL, p<0.001). The pathway analysis revealed a statistically significant enrichment of genes in the tumour necrosis factor signalling pathway driven by rare damaging variants inRELB,RELAandRELusing higher criticism test weighted by eigenvector centrality.ConclusionsThis study identified specific rare variants in theDCBLD2gene as a putative genetic risk factor for RP. These findings should be validated in additional patients with RP and supported by future functional experiments.

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Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 55%

Ultra-rare genetic variation in relapsing polychondritis: a whole-exome sequencing study

Luo,

Ferrada,

Sikora

et al. 2023

Ann Rheum Dis

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“…Patients with MAGIC syndrome exhibit clinical features of both BD and RP. A prospective cohort study demonstrated good sensitivity in classifying patients according to McAdam’s or Damiani’s Criteria for RP and the International Criteria for BD ( 130 ). Interestingly, in this study, RP patients with MAGIC syndrome demonstrated higher frequency of anti-type 2 collagen autoantibodies than in those without MAGIC syndrome.…”

Section: Mouth and Genital Ulcers With Inflamed Cartilage Syndromementioning

confidence: 99%

Innate immune responses in Behçet disease and relapsing polychondritis

et al. 2023

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Behçet disease (BD) and relapsing polychondritis (RP) are chronic multisystem disorders characterized by recurrent flare-ups of tissue inflammation. Major clinical manifestations of BD are oral aphthae, genital aphthous ulcers, skin lesions, arthritis, and uveitis. Patients with BD may develop rare but serious neural, intestinal, and vascular complications, with high relapse rates. Meanwhile, RP is characterized by the inflammation of the cartilaginous tissues of the ears, nose, peripheral joints, and tracheobronchial tree. Additionally, it affects the proteoglycan-rich structures in the eyes, inner ear, heart, blood vessels, and kidneys. The mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome is a common characteristic of BD and RP. The immunopathology of these two diseases may be closely related. It is established that the genetic predisposition to BD is related to the human leukocyte antigen (HLA)-B51 gene. Skin histopathology demonstrates the overactivation of innate immunity, such as neutrophilic dermatitis/panniculitis, in patients with BD. Monocytes and neutrophils frequently infiltrate cartilaginous tissues of patients with RP. Somatic mutations in UBA1, which encodes a ubiquitylation-related enzyme, cause vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS) with severe systemic inflammation and activation of myeloid cells. VEXAS prompts auricular and/or nasal chondritis, with neutrophilic infiltration around the cartilage in 52–60% of patients. Thus, innate immune cells may play an important role in the initiation of inflammatory processes underlying both diseases. This review summarizes the recent advances in our understanding of the innate cell-mediated immunopathology of BD and RP, with a focus on the common and distinct features of these mechanisms.

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Secondary Raynaud’s Phenomenon: Focus on Rheumatic Diseases

Ong,

Denton

2024

Raynaud’s Phenomenon

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A prospective observational cohort study and systematic review of 40 patients with mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome

Cited by 9 publications

References 30 publications

Ultra-rare genetic variation in relapsing polychondritis: a whole-exome sequencing study

Ultra-rare genetic variation in relapsing polychondritis: a whole-exome sequencing study

Innate immune responses in Behçet disease and relapsing polychondritis

Secondary Raynaud’s Phenomenon: Focus on Rheumatic Diseases

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