title: Development of positive antinuclear antibodies and rheumatoid factor in systemic juvenile idiopathic arthritis points toward an autoimmune phenotype later in the disease course.
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.
  
  
  RESULTS
  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.
authors.affiliation: German Center for Pediatric and Adolescent Rheumatology, Gehfeldstrasse 24, 82467 Garmisch-Partenkirchen, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Hügle
authors.affiliation: German Center for Pediatric and Adolescent Rheumatology, Gehfeldstrasse 24, 82467 Garmisch-Partenkirchen, Germany ; Department of Pediatric Rheumatology and Immunology, University Children's Hospital Münster, Münster, Germany.
authors.forename: Claas
authors.initials: C
authors.lastname: Hinze
authors.affiliation: Department of Pediatric Rheumatology, University Duisburg-Essen, Children's Hospital, Essen, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Lainka
authors.affiliation: German Center for Pediatric and Adolescent Rheumatology, Gehfeldstrasse 24, 82467 Garmisch-Partenkirchen, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Fischer
authors.affiliation: German Center for Pediatric and Adolescent Rheumatology, Gehfeldstrasse 24, 82467 Garmisch-Partenkirchen, Germany.
authors.forename: Johannes-Peter
authors.initials: JP
authors.lastname: Haas
mesh_terms: D000974:Antibodies, Antinuclear / Q000097:blood*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D001327:Autoimmune Diseases / Q000097:blood / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006306:Health Surveys; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D012217:Rheumatoid Factor / Q000097:blood*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000974:Antibodies, Antinuclear; D018501:Antirheumatic Agents; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D012217:Rheumatoid Factor
keywords: Antinuclear antibodies; Juvenile idiopathic arthritis; Juvenile systemic arthritis; Rheumatoid factor - autoimmunity
references.citation: Arthritis Rheum. 2000 Mar;43(3):628-37
references.pmid: 10728757
references.citation: J Rheumatol. 1997 Mar;24(3):568-75
references.pmid: 9058667
references.citation: Ann Rheum Dis. 2011 May;70(5):747-54
references.pmid: 21173013
references.citation: Arthritis Rheum. 1989 Jul;32(7):877-83
references.pmid: 2787640
references.citation: Rheumatology (Oxford). 2011 Jan;50(1):237-42
references.pmid: 21148158
references.citation: Nat Rev Rheumatol. 2011 Jun 07;7(7):416-26
references.pmid: 21647204
references.citation: PLoS Med. 2006 Aug;3(8):e297
references.pmid: 16942393
references.citation: Eur J Pediatr. 1981 Feb;135(3):225-8
references.pmid: 7194797
references.citation: Arthritis Rheum. 2009 Jul;60(7):2102-12
references.pmid: 19565513
references.citation: J Rheumatol. 1998 Jul;25(7):1388-98
references.pmid: 9676774
references.citation: Arthritis Rheum. 2007 Jun;56(6):1954-65
references.pmid: 17530721
references.citation: Arthritis Rheum. 2006 May;54(5):1595-601
references.pmid: 16645998
references.citation: Ann Rheum Dis. 2008 Mar;67(3):302-8
references.pmid: 17947302
references.citation: J Rheumatol. 2004 Feb;31(2):390-2
references.pmid: 14760812
references.citation: Pediatrics. 1992 Mar;89(3):441-4
references.pmid: 1741219
references.citation: Arthritis Rheum. 2011 Feb;63(2):545-55
references.pmid: 21280009
references.citation: Arthritis Rheum. 2007 Nov;56(11):3793-804
references.pmid: 17968951
references.citation: Arthritis Rheum. 2012 Jul;64(7):2319-27
references.pmid: 22237992
references.citation: J Clin Rheumatol. 2009 Jun;15(4):161-4
references.pmid: 19363453
references.citation: J Rheumatol. 1990 Jul;17(7):936-40
references.pmid: 2213760
references.citation: Ann Rheum Dis. 1992 Dec;51(12):1301-6
references.pmid: 1485811
references.citation: Arthritis Rheum. 2009 Jul;60(7):2113-23
references.pmid: 19565504
references.citation: Ann Rheum Dis. 2012 Jun;71(6):974-80
references.pmid: 22267331
references.citation: J Exp Med. 2007 Sep 3;204(9):2131-44
references.pmid: 17724127
references.citation: Arthritis Rheum. 2000 Apr;43(4):944
references.pmid: 10765944