Immunoglobulin gene polymorphisms are susceptibility factors in clinical and autoantibody subgroups of the idiopathic inflammatory myopathies

O’Hanlon, Terrance P.; Rider, Lisa G.; Schiffenbauer, Adam; Targoff, Ira N.; Malley, Karen G.; Pandey, Janardan P.; Miller, Frederick W.

doi:10.1002/art.23899

Cited by 41 publications

(28 citation statements)

References 33 publications

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“…Some differences in autoantibodies and clinical expression of juvenile myositis have been described, such as anti-SRP antibodies, which is associated with Black race, severe disease and juvenile polymyositis. 35 Differences in immune response genes between races have also been described in JDM 36 . Thus, our findings support the concept that JDM is a multifactorial, complex autoimmune disorder with a genetic contribution.…”

Section: Discussionmentioning

confidence: 96%

Race, Income, and Disease Outcomes in Juvenile Dermatomyositis

Phillippi

Hoeltzel

Kim

et al. 2017

The Journal of Pediatrics

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Objective To determine the relationship between race, income, and disease outcomes in children with juvenile dermatomyositis (JDM). Study design Data from 438 subjects with JDM enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry were analyzed. Demographic data included age, sex, race, income and insurance status. Clinical outcomes included muscle strength, presence of rash, calcinosis, weakness, physical function and quality of life measures. Disease outcomes were compared based on race and income. Results Minority subjects were significantly more likely to have low family income, and significantly worse scores on measures of physical function, disease activity and quality of life measures. Lower income subjects had worse scores on measures of physical function, disease activity and quality of life scores, as well as weakness. Black subjects were more likely to have calcinosis. Despite these differences in outcome measures, there were no significant differences in time to diagnosis or disease duration. Using calcinosis as a marker of disease morbidity, Black race, annual family income less than $50,000 per year, negative ANA, and delay in diagnosis greater than 12 months were associated with calcinosis. Conclusions Minority race and lower income are associated with worse morbidity and outcomes in subjects with JDM. Calcinosis was more common in Black subjects. Future studies are needed to further understand these associations so that efforts may be developed to address health disparities in subjects with JDM and improve disease outcomes.

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Section: Discussionmentioning

confidence: 96%

Race, Income, and Disease Outcomes in Juvenile Dermatomyositis

Phillippi

Hoeltzel

Kim

et al. 2017

The Journal of Pediatrics

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“…Caucasian patients with JDM also have several protective alleles, including DQA1*0201, DQA1*0101, and DQA1*0102 [19], which are less frequent in affected patients than in healthy controls and may mechanistically contribute to disease development through binding of self-reactive antigens and the elimination of self-reactive T lymphocytes from the thymus. Several other polymorphic loci have been shown to be risk factors for JDM, including the pro inflammatory cytokine genes TNFα [16, 22], IL-1α and IL-1β [16], the lymphocyte signalling gene PTPN22 [23] and phenotypes of the immunoglobulin heavy chain [24]. The TNFα variant known as TNF308A carries a higher risk of calcinosis and ulcerations [16, 22], and in controls this genotype is associated with higher levels of TNF production [25].…”

Section: Aetiology and Pathogenesis Of Jdmmentioning

confidence: 99%

Juvenile dermatomyositis: new developments in pathogenesis, assessment and treatment

Wedderburn¹,

Rider²

2009

Best Practice & Research Clinical Rheumatology

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110

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Juvenile dermatomyositis (JDM) is a rare, potentially life-threatening systemic autoimmune disease primarily affecting muscle and skin. Recent advances in the recognition, standardised assessment and treatment of JDM have been greatly facilitated by large collaborative research networks. Through these networks, a number of immunogenetic risk factors have now been defined, as well as a number of potential pathways identified in the aetio-pathogenesis of JDM. Myositis-associated and myositisspecific autoantibodies are helping to sub-phenotype JDM, defined by clinical features, outcomes and immunogenetic risk factors. Partially validated tools to assess disease activity and damage have assisted in standardising outcomes. Aggressive treatment approaches, including multiple initial therapies, as well as new drugs and biologic therapies for refractory disease, offer promise of improved outcomes and less corticosteroid-related toxicity.

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“…This included alleles and genotypes of TNF-α (−308 and −238), interleukin (IL)-1α (−889 and +4845), and IL-1β (−511 and +3953) (12), MHC DRB1 and DQA1 alleles and binding motifs (19), and immunoglobulin allotypes and phenotypes (20). …”

Section: Methodsmentioning

confidence: 99%

Brief Report: Association of Myositis Autoantibodies, Clinical Features, and Environmental Exposures at Illness Onset With Disease Course in Juvenile Myositis

Habers

Huber

Mamyrova

et al. 2016

Arthritis & Rheumatology

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Objective To identify early factors associated with disease course in patients with juvenile idiopathic inflammatory myopathies (JIIM). Methods Univariable and multivariable multinomial logistic regression analyses were performed in a large JIIM registry (n=365), including demographics, early clinical features, serum muscle enzyme levels, myositis autoantibodies, environmental exposures, and immunogenetic polymorphisms. Results Multivariable associations with chronic or polycyclic courses compared to monocyclic included myositis-specific autoantibodies (multinomial odds ratio (M-OR) 4.2 and 2.8, respectively), myositis-associated autoantibodies (M-OR 4.8 and 3.5), and a documented infection within six months of illness onset (M-OR 2.5 and 4.7). A higher overall clinical symptom score at diagnosis was associated with chronic or monocyclic courses compared to polycyclic. Furthermore, a severe illness onset was associated with chronic compared to monocyclic or polycyclic courses (M-OR 2.1 and 2.6), while anti-p155/140 autoantibodies were associated with chronic or polycyclic courses compared to monocyclic (M-OR 3.9 and 2.3). Additional univariable associations of chronic compared to monocyclic course included photosensitivity, “V-sign” or “Shawl-sign” rashes, and cuticular overgrowth (OR 2.2–3.2). The mean and highest ultraviolet index in the month before diagnosis were associated with a chronic compared to polycyclic course in boys (OR 1.3 and 1.5), while residing in the Northwest was less frequently associated with a chronic course (OR 0.2). Conclusion Myositis autoantibodies, in particular anti-p155/140, and a number of early clinical features and environmental exposures were associated with a chronic course in patients with JIIM. These findings suggest early factors can be identified that are associated with poorer outcomes in JIIM.

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Immunoglobulin gene polymorphisms are susceptibility factors in clinical and autoantibody subgroups of the idiopathic inflammatory myopathies

Cited by 41 publications

References 33 publications

Race, Income, and Disease Outcomes in Juvenile Dermatomyositis

Race, Income, and Disease Outcomes in Juvenile Dermatomyositis

Juvenile dermatomyositis: new developments in pathogenesis, assessment and treatment

Brief Report: Association of Myositis Autoantibodies, Clinical Features, and Environmental Exposures at Illness Onset With Disease Course in Juvenile Myositis

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