1. Introduction

Celiac disease is an autoimmune condition ^[1]. Autoimmune rheumatologic diseases with juvenile onset are intensively studied in recent years ^[2]. Is there a connection between celiac disease and arthritis? The presence of celiac disease (CD) in patients with juvenile arthritis was revealed in 2008 ^[3]. So the question was, if juvenile arthritis could be associated with other autoimmune diseases with similar genetic background ^[4]. There was a 5-10 increased risk of CD coexistence with other autoimmune diseases, such as type I diabetes mellitus (T1DM), juvenile arthritis or autoimmune thyroiditis ^[5]. A patient with rare association of juvenile arthritis with CD was reported later in 2011. So, again the question was, if juvenile arthritis could be associated with other autoimmune diseases ^[6]. But association of CD with juvenile arthritis was for a long time an enigma ^[7]. The clinical data about CD association with juvenile arthritis were few. We will analyze in this article the evidence given by serological and genetic testing related to CD association with juvenile arthritis and rheumatoid arthritis.

2. Serological Testing

Mayouf et al. revealed that positive anti-endomisium antibodies (EmA) needed further investigations for CD diagnosis among children with juvenile arthritis ^[8] Koehne et al. concluded that positive anti-gliadin (AGA) IgA, AGA IgG or EmA results are probably nonspecific for the CD presence among rheumatologic disease patients ^[9]. AGA were more often detected in rheumatoid arthritis patients and primary Sjögren's syndrome patients than in the general population ^[10]. Anti-tissular transglutaminase antibodies (tTG) were a useful screening test to find asymptomatic CD associated with active juvenile arthritis ^[11]. However, other study concluded that high levels of tTG IgA in patients with juvenile arthritis reflected increased polyclonal IgA production, not a specific intestinal inflammatory process. ^[12]. Therefore, the patients with juvenile arthritis needed a screening protocols for CD ^[13]. The screening of CD showed many associations of CD. But the evidence provided by the screening of CD in juvenile arthritis were also few.

3. Genetic Testing

The 4q27 locus was related with susceptibility to juvenile arthritis. This locus was also associated with rheumatoid arthritis, T1DM, CD, and psoriatic arthritis ^[14]. One SNP in the LPP gene, rs1464510 and a second SNP, rs653178 in ATXN2, showed association with juvenile arthritis. Association at the SH2B3/ATXN2 locus, also supported this region to JIA susceptibility ^[15]. PTPN22 gene was also related to susceptibility to some autoimmune diseases ^[16]. The pattern diseases are important for managing the entryway diseases ^[17].

Human leukocyte antigen (HLA) testing contributed to understanding CD pathogenesis compared to T1DM, multiple sclerosis, and rheumatoid arthritis ^[18]. Gluten-specific T cells utilises T cell repertoire (TCR) in HLA-DQ2(+) and HLA-DQ8(+) patients. Similar mechanisms are likely to play a role in rheumatoid arthritis ^[19]. But association of specific HLA molecules in rheumatoid arthritis remains poorly defined and an immune response against post-translationally modified protein antigens is a hallmark of each disease ^[20]. The diseases also share multiple non-HLA loci that are crucial for activation and regulation of adaptive and innate immunity ^[21]. Gutierrez-Achury et al. discovered five new non-HLA loci shared by CD and rheumatoid arthritis. They also found that in nine of 24 shared loci the associated variants are distinct in the two diseases ^[22].

4. Conclusions

Serological testing have not helped too much in the diagnosis of CD in juvenile arthritis but genetic testing are important for monitoring of CD genetic risk in rheumatoid arthritis and juvenile arthritis.

References

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