MEFV Mutations in Egyptian Children with Systemic-Onset Juvenile Idiopathic Arthritis

Lotfy, Hayam M.; Kandil, Manal E.; Issac, Marianne Samir M.; Salah, Samia; Ismail, Nagwa Abdallah; Mawla, Mohamed A. Abdel

doi:10.1007/s40291-014-0105-4

Cited by 8 publications

(8 citation statements)

References 36 publications

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“…Since it has been suggested that systemic onset JIA should be considered an autoinflammatory condition, it is not surprising that genetic variants associated with inherited forms of auto-inflammatory syndromes have been associated with systemic JIA [91,92]. These include SNPs in the interleukin 1 ligand cluster, TNFRSF1A and MVK genes.…”

Section: Genetics Of Systemic Onset Jiamentioning

confidence: 99%

Immunogenetics of juvenile idiopathic arthritis: A comprehensive review

Hersh

Prahalad

2015

Journal of Autoimmunity

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 Systemic Onset Jiamentioning

confidence: 99%

Immunogenetics of juvenile idiopathic arthritis: A comprehensive review

Hersh

Prahalad

2015

Journal of Autoimmunity

118

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“…The MEFV gene is also responsible for familial Mediterranean fever, which is an autosomal recessive disorder [13]. Multiple mutations (polymorphisms) of the MEFV gene in one allele have been reported in patients with SJIA [7–9, 14]. The present patient only had a heterozygous E148Q mutation in the MEFV gene, which is a common polymorphism.…”

Section: Discussionmentioning

confidence: 72%

“…The MEFV gene encodes a protein called pyrin or marenostrin, which inhibits the processing of IL-1β to an active form through the regulation of nuclear factor-KB and caspase-1 [9]. Pyrin deficiency results in uncontrolled production of active IL-1β [13].…”

Section: Discussionmentioning

confidence: 99%

“…Whether the E148Q polymorphism is a benign or disease-causing mutation remains controversial. Although glutamic acid has been conserved at position 148 throughout evolution, thus favoring mutation, the general populations of many ethnicities exhibit a high frequency of E148Q (Egyptian, 6.66%; Jewish, 4.30%–6.60%; Greek, 1.30%; Japanese, 23.70% [9, 14–16]; and Thai, 24.3% [unpublished data]). Without other polymorphisms in the MEFV gene, the presentation of amyloidosis of our patient may or may not have been related to the heterozygous E148Q mutation.…”

Section: Discussionmentioning

confidence: 99%

“…However, amyloidosis is still a rare complication in patients with JIA and other rheumatic diseases [5, 6]. Many previous studies have revealed that common heterozygous or homozygous mutations in the MEFV gene are associated with systemic-onset JIA (SJIA) [7–9]. We herein report a case involving an adolescent female patient who was diagnosed with SJIA and developed progressive proteinuria.…”

Section: Introductionmentioning

confidence: 98%

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Clinical improvement of renal amyloidosis in a patient with systemic-onset juvenile idiopathic arthritis who received tocilizumab treatment: a case report and literature review

et al. 2017

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BackgroundJuvenile idiopathic arthritis (JIA) is a common rheumatic disease in children and adolescents. Although JIA may cause secondary amyloidosis, this is a rare complication in patients with JIA and other rheumatic diseases. Many previous studies have revealed that common heterozygous or homozygous mutations in the MEFV gene are associated with systemic-onset JIA (SJIA).Case presentationWe herein report a case involving a 19-year-old female patient with difficult-to-control SJIA. She developed progressive proteinuria without clinical signs or symptoms of edema. Renal amyloidosis was diagnosed by renal pathologic examination, which demonstrated deposition of eosinophilic amorphous material in the interlobular arteries, arterioles, and interstitium. Electron microscopy showed fibrillary material deposits with a diameter of 8 to 10 nm. A heterozygous E148Q mutation in the MEFV gene was identified. Conventional disease-modifying anti-rheumatic drugs and etanercept had been used to treat the SJIA, but the disease could not be controlled. Therefore, we decided to start tocilizumab to control the disease activity. However, the patient was unable to receive a standard dose of tocilizumab in the early period of treatment because of socioeconomic limitations. Her disease course was still active, and proteinuria was found. Therefore, tocilizumab was increased to a dose of 8 mg/kg every 2 weeks (standard dose of SJIA), and the patient exhibited a clinical response within 3 months.ConclusionRefractory SJIA associated with renal amyloidosis is an uncommon cause of proteinuria in adolescents. Tocilizumab may be a beneficial treatment for renal amyloidosis in patients with SJIA.

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