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Development of positive antinuclear antibodies and rheumatoid factor in systemic juvenile idiopathic arthritis points toward an autoimmune phenotype later in the disease course.

Hügle B, Hinze C, Lainka E, Fischer N, Haas JP - Pediatr Rheumatol Online J (2014)

Bottom Line: A retrospective chart survey was used to extract demographic and clinical data as well as presence and titers of ANA and RF at diagnosis and during follow-up. 32 patients were included in the study, with a median age of 4.2 years and median follow-up of 6.0 years. 8/32 patients had ANA titers ≥ 1:80 at diagnosis, with 22/32 patients showing rising ANA titers with titers ≥ 1:80 at last follow-up (p =0.001). 10/32 patients had a positive RF at least once during follow-up, compared to 0/32 at diagnosis (p = 0.001).In 5/10 patients, positive RF was documented at least twice, more than twelve weeks apart.Patients treated with TNF antagonists were not significantly more likely to develop positive ANA titers (p = 0.425) or positive RF (p = 0.703).

View Article: PubMed Central - HTML - PubMed

Affiliation: German Center for Pediatric and Adolescent Rheumatology, Gehfeldstrasse 24, 82467 Garmisch-Partenkirchen, Germany.

ABSTRACT

Background: Systemic juvenile idiopathic arthritis (sJIA) is commonly considered an autoinflammatory disease. However, sJIA patients may develop aggressive arthritis without systemic inflammation later in the disease, resembling an autoimmune phenotype similar to other subtypes of JIA. The objective of this study was to determine whether antinuclear antibodies (ANA) and rheumatoid factor (RF) will develop in patients with sJIA over the course of the disease.

Findings: A single center sample of sJIA patients with follow-up of more than one year was obtained. A retrospective chart survey was used to extract demographic and clinical data as well as presence and titers of ANA and RF at diagnosis and during follow-up. 32 patients were included in the study, with a median age of 4.2 years and median follow-up of 6.0 years. 8/32 patients had ANA titers ≥ 1:80 at diagnosis, with 22/32 patients showing rising ANA titers with titers ≥ 1:80 at last follow-up (p =0.001). 10/32 patients had a positive RF at least once during follow-up, compared to 0/32 at diagnosis (p = 0.001). In 5/10 patients, positive RF was documented at least twice, more than twelve weeks apart. Patients treated with TNF antagonists were not significantly more likely to develop positive ANA titers (p = 0.425) or positive RF (p = 0.703).

Conclusions: Patients with sJIA developed increased ANA titers and positive RF over the course of the disease, independent of treatment with TNF antagonists. This might point towards an autoimmune, rather than an autoinflammatory phenotype later in the course of sJIA.

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Concept schematic of the different disease courses of systemic juvenile idiopathic arthritis. The lower curve shows the postulated two phases of persistent disease course, with initially predominant systemic disease and development of chronic polyarthritis later in the disease course.
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Figure 2: Concept schematic of the different disease courses of systemic juvenile idiopathic arthritis. The lower curve shows the postulated two phases of persistent disease course, with initially predominant systemic disease and development of chronic polyarthritis later in the disease course.

Mentions: The prodromal, systemic phase of sJIA appears to correlate well with a massive activation of the innate immune system, as indicated e.g. by PBMC gene expression studies showing marked upregulation and/or overrepresentation of innate immune signaling pathways, downregulation of adaptive immunity signaling pathways, and extremely elevated MRP8/14 levels[16,17]. Taking into account the clinical picture, the lack of female preponderance, the lack of HLA class II associations, the general lack of autoantibodies in this disease phase and an excellent response to IL-1 and IL-6 blockade, sJIA may well be regarded as a 'pure’ autoinflammatory syndrome. This leads to the question: How and why is there, in a substantial proportion of patients, a transition to an aggressive polyarthritis, often with cessation of the extreme systemic inflammation initially observed? The presence of increasing autoantibody titers demonstrated here supports the hypothesis that the initial inflammatory phenotype of sJIA might induce B- and T-cell mediated autoimmunity later in the disease, for example via downstream activation of antigen presentation. Figure 2 illustrates this postulated mechanism of a two-phased disease course, with initial systemic disease driven by autoinflammatory processes, and ongoing arthritis caused by autoimmunity. Whether or not this observation is pathogenically relevant or merely an epiphenomenon representative of nonspecific polyclonal activation is unclear and cannot be answered by this study.


Development of positive antinuclear antibodies and rheumatoid factor in systemic juvenile idiopathic arthritis points toward an autoimmune phenotype later in the disease course.

Hügle B, Hinze C, Lainka E, Fischer N, Haas JP - Pediatr Rheumatol Online J (2014)

Concept schematic of the different disease courses of systemic juvenile idiopathic arthritis. The lower curve shows the postulated two phases of persistent disease course, with initially predominant systemic disease and development of chronic polyarthritis later in the disease course.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4127434&req=5

Figure 2: Concept schematic of the different disease courses of systemic juvenile idiopathic arthritis. The lower curve shows the postulated two phases of persistent disease course, with initially predominant systemic disease and development of chronic polyarthritis later in the disease course.
Mentions: The prodromal, systemic phase of sJIA appears to correlate well with a massive activation of the innate immune system, as indicated e.g. by PBMC gene expression studies showing marked upregulation and/or overrepresentation of innate immune signaling pathways, downregulation of adaptive immunity signaling pathways, and extremely elevated MRP8/14 levels[16,17]. Taking into account the clinical picture, the lack of female preponderance, the lack of HLA class II associations, the general lack of autoantibodies in this disease phase and an excellent response to IL-1 and IL-6 blockade, sJIA may well be regarded as a 'pure’ autoinflammatory syndrome. This leads to the question: How and why is there, in a substantial proportion of patients, a transition to an aggressive polyarthritis, often with cessation of the extreme systemic inflammation initially observed? The presence of increasing autoantibody titers demonstrated here supports the hypothesis that the initial inflammatory phenotype of sJIA might induce B- and T-cell mediated autoimmunity later in the disease, for example via downstream activation of antigen presentation. Figure 2 illustrates this postulated mechanism of a two-phased disease course, with initial systemic disease driven by autoinflammatory processes, and ongoing arthritis caused by autoimmunity. Whether or not this observation is pathogenically relevant or merely an epiphenomenon representative of nonspecific polyclonal activation is unclear and cannot be answered by this study.

Bottom Line: A retrospective chart survey was used to extract demographic and clinical data as well as presence and titers of ANA and RF at diagnosis and during follow-up. 32 patients were included in the study, with a median age of 4.2 years and median follow-up of 6.0 years. 8/32 patients had ANA titers ≥ 1:80 at diagnosis, with 22/32 patients showing rising ANA titers with titers ≥ 1:80 at last follow-up (p =0.001). 10/32 patients had a positive RF at least once during follow-up, compared to 0/32 at diagnosis (p = 0.001).In 5/10 patients, positive RF was documented at least twice, more than twelve weeks apart.Patients treated with TNF antagonists were not significantly more likely to develop positive ANA titers (p = 0.425) or positive RF (p = 0.703).

View Article: PubMed Central - HTML - PubMed

Affiliation: German Center for Pediatric and Adolescent Rheumatology, Gehfeldstrasse 24, 82467 Garmisch-Partenkirchen, Germany.

ABSTRACT

Background: Systemic juvenile idiopathic arthritis (sJIA) is commonly considered an autoinflammatory disease. However, sJIA patients may develop aggressive arthritis without systemic inflammation later in the disease, resembling an autoimmune phenotype similar to other subtypes of JIA. The objective of this study was to determine whether antinuclear antibodies (ANA) and rheumatoid factor (RF) will develop in patients with sJIA over the course of the disease.

Findings: A single center sample of sJIA patients with follow-up of more than one year was obtained. A retrospective chart survey was used to extract demographic and clinical data as well as presence and titers of ANA and RF at diagnosis and during follow-up. 32 patients were included in the study, with a median age of 4.2 years and median follow-up of 6.0 years. 8/32 patients had ANA titers ≥ 1:80 at diagnosis, with 22/32 patients showing rising ANA titers with titers ≥ 1:80 at last follow-up (p =0.001). 10/32 patients had a positive RF at least once during follow-up, compared to 0/32 at diagnosis (p = 0.001). In 5/10 patients, positive RF was documented at least twice, more than twelve weeks apart. Patients treated with TNF antagonists were not significantly more likely to develop positive ANA titers (p = 0.425) or positive RF (p = 0.703).

Conclusions: Patients with sJIA developed increased ANA titers and positive RF over the course of the disease, independent of treatment with TNF antagonists. This might point towards an autoimmune, rather than an autoinflammatory phenotype later in the course of sJIA.

Show MeSH
Related in: MedlinePlus