Limitations in the Classification of Childhood-onset Rheumatoid Arthritis

Ferrell, Emily G.; Ponder, Lori; Minor, Lauren S.; Angeles‐Han, Sheila T.; Kennedy, Christine; Rouster‐Stevens, Kelly; Rohani-Pichavant, Mina; Vogler, Larry B.; Prahalad, Sampath

doi:10.3899/jrheum.130563

Cited by 17 publications

(7 citation statements)

References 13 publications

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“…In order to improve the sensitivity of diagnosing childhood-onset RA, we have proposed prioritization of RF/anti-CCP positivity over specific exclusions (e.g. number of joints involved), along with inclusion of anti-CCP, in future revisions of the JIA classification criteria [65]. Thus, some of the following genetic associations described might include all children with RF/CCP positive JIA, albeit a substantial majority of them would fall under the polyarticular RF-positive JIA category defined by the ILAR criteria.…”

Section: Genetics Of Polyarticular Rf-positive Jiamentioning

confidence: 99%

Immunogenetics of juvenile idiopathic arthritis: A comprehensive review

Hersh

Prahalad

2015

Journal of Autoimmunity

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118

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Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory arthropathy of childhood. Juvenile idiopathic arthritis is believed to be a complex genetic trait influenced by both genetic and environmental factors. Twin and family studies suggest a substantial role for genetic factors in the predisposition to JIA. Describing the genetics is complicated by the heterogeneity of JIA; the International League of Associations for Rheumatology (ILAR) has defined seven categories of JIA based on distinct clinical and laboratory features. Utilizing a variety of techniques including candidate gene studies, the use of genotyping arrays such as Immunochip, and genome wide association studies (GWAS), both human leukocyte antigen (HLA) and non-HLA susceptibility loci associated with JIA have been described. Several of these polymorphisms (e.g. HLA class II, PTPN22, STAT4) are shared with other common autoimmune conditions; other novel polymorphisms that have been identified may be unique to JIA. Associations with oligoarticular and RF-negative polyarticular JIA are the best characterized. A strong association between HLA DRB1:11:03/04 and DRB1:08:01, and a protective effect of DRB1:15:01 have been described. HLA DPB1:02:01 has also been associated with oligoarticular and RF-negative polyarticular JIA. Besides PTPN22, STAT4 and PTPN2 variants, IL2, IL2RA, IL2RB, as well as IL6 and IL6R loci also harbor variants associated with oligoarticular and RF-negative polyarticular JIA. RF-positive polyarticular JIA is associated with many of the shared epitope encoding HLA DRB1 alleles, as well as PTPN22, STAT4 and TNFAIP3 variants. ERA is associated with HLA B27. Most other associations between JIA categories and HLA or non-HLA variants need confirmation. The formation of International Consortia to ascertain and analyze large cohorts of JIA categories, validation of reported findings in independent cohorts, and functional studies will enhance our understanding of the genetic underpinnings of JIA.

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Section: Genetics Of Polyarticular Rf-positive Jiamentioning

confidence: 99%

Immunogenetics of juvenile idiopathic arthritis: A comprehensive review

Hersh

Prahalad

2015

Journal of Autoimmunity

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118

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“…About 5 % of children with juvenile idiopathic arthritis (JIA) have a disease that phenotypically resembles RA, characterized by chronic inflammatory arthritis and the presence of RF and/or CCP. Such children likely represent a subset of seropositive RA patients with childhood onset of RA [ 1 ]. It is not known if childhood onset RA shares the same risk factors associated with adult-onset RA.…”

Section: Introductionmentioning

confidence: 99%

Symptoms of periodontitis and antibody responses to Porphyromonas gingivalis in juvenile idiopathic arthritis

et al. 2016

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BackgroundThe association between rheumatoid arthritis (RA) and periodontitis is well established. Some children with juvenile idiopathic arthritis (JIA) phenotypically resemble adults with RA, characterized by the presence of anti-cyclic citrullinated peptide (CCP) antibodies. We sought to investigate an association between CCP-positive JIA and symptoms of periodontitis and antibodies to oral microbiota.MethodsAntibodies to oral pathogens Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum were measured using ELISA in 71 children with CCP-positive JIA and 74 children with CCP-negative JIA. Oral health history was collected from 37 children with CCP-positive JIA and 121 children with CCP-negative JIA. T-tests, Chi-square tests, Mann–Whitney U tests, and multivariable regression were used to compare the groups.ResultsCompared to those with CCP-negative JIA, children with CCP-positive JIA were more likely to be female, older and non-Caucasian. Anti-P. gingivalis (p <0.003) and anti-P. intermedia (p <0.008) IgG antibody titers were higher in the CCP-positive cohort. Differences in P. gingivalis antibody titers remained significant after adjusting for age (p = 0.007). Children with CCP-positive JIA more likely reported tender/bleeding gums (43 % vs. 24 %, p < 0.02) compared to children with CCP-negative JIA. After controlling for age at collection, the odds of having tender/bleeding gums were 2.2 times higher in the CCP-positive group compared (95 % CI 0.98 – 4.83; p = 0.056).ConclusionsChildren with CCP-positive JIA have higher antibody titers to P. gingivalis and more symptoms of poor oral health, supporting a possible role for periodontitis in the etiology of CCP-positive JIA.

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“…4,5 As more advances occur in genomics, proteomics, and metabolomics, the utility and need to modify current classification schemes for autoinflammatory and autoimmune conditions will be clearer.…”

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confidence: 99%

Juvenile Idiopathic Arthritis Overview and Involvement of the Temporomandibular Joint

Carrasco

2015

Oral and Maxillofacial Surgery Clinics of North America

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Limitations in the Classification of Childhood-onset Rheumatoid Arthritis

Cited by 17 publications

References 13 publications

Immunogenetics of juvenile idiopathic arthritis: A comprehensive review

Immunogenetics of juvenile idiopathic arthritis: A comprehensive review

Symptoms of periodontitis and antibody responses to Porphyromonas gingivalis in juvenile idiopathic arthritis

Juvenile Idiopathic Arthritis Overview and Involvement of the Temporomandibular Joint

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