Biomarkers in systemic juvenile idiopathic arthritis

Abstract

Purpose of review This review summarizes biomarkers in Systemic Juvenile Idiopathic Arthritis (sJIA). Broadly, the markers are classified under protein, cellular, gene expression and genetic markers. We also compare the biomarkers in sJIA to biomarkers in cryopyrin associated periodic syndromes (CAPS). Recent findings Recent publications showing the similarity of clinical response of sJIA and CAPS to anti IL1 therapies prompted a comparison at the biomarker level. Summary sJIA traditionally is classified under the umbrella of juvenile idiopathic arthritis. At the clinical phenotypic level, sJIA has several features that are more similar to those seen in Cryopyrin Associated Periodic Syndromes (CAPS). In this review, we summarize biomarkers in sJIA and CAPS and draw upon the various similarities and differences between the two families of diseases. The main difference between sJIA and CAPS biomarkers are genetic markers with CAPS being a family of monogenic diseases with mutations in NLRP3. There have been a small number of publications describing cellular biomarkers in sJIA with no such studies described for CAPS. Many of the protein markers characteristic of sJIA are also seen to characterize CAPS. The gene expression data in both sJIA and CAPS show a strong upregulation of innate immunity pathways. In addition, we describe a strong similarity between sJIA and CAPS at the gene expression level where several genes that form a part of the erythropoiesis signature are upregulated in both sJIA and CAPS.

Diagnosis and Management of the Cryopyrin-Associated Periodic Syndromes (CAPS): What Do We Know Today?

“…Particularly, SAA is one crucial parameter to detect subclinical inflammation and risk evaluation for the development of AA-amyloidosis [ 87 ]. Additionally, S100A12 and MRP8/MRP14 can be used for the monitoring of inflammation with a good correlation to inflammation and treatment response [ 86 , 88 ]. Other disorders associated with recurrent systemic inflammation, such as immunodeficiencies, infections, autoimmune diseases, and malignancies, need to be excluded.…”

S100A8/A9, a potent serum and molecular imaging biomarker for synovial inflammation and joint destruction in seronegative experimental arthritis

“…The search for more reliable biomarkers for seronegative arthritis has resulted in several serum proteins that are associated with disease activity in patients with seronegative arthritis: IL-6, IL-17, IL-23, VEGF, and MMP3 in SpA [6, 7, 40–43], and IL-6 and IL-18 in JIA [5, 36, 44], amongst others. Although these proteins correlate with certain clinical aspects of seronegative arthritis, a major problem remains the lack of specificity, and results are often inconsistent; moreover, these putative biomarkers still await validation in cohort studies.…”

“…Currently, a considerable number of studies are exploring the potential of new diagnostic and predictive markers for several forms of seronegative arthritis, including calprotectin (S100A8/A9) [5–7]. Whereas in RA serum S100A8/A9 has been widely accepted as a powerful serum biomarker to assess disease activity and to predict therapy response [8], its role as a serum biomarker in seronegative arthritis is still under investigation [9–12].…”

Lipopolysaccharide stimulation test on cultured PBMCs assists the discrimination of cryopyrin-associated periodic syndrome from systemic juvenile idiopathic arthritis

“…Additionally, around 6.7%–13% of the patients with sJIA experienced a potentially fatal condition, macrophage activation syndrome (MAS), portrayed by persistent fever, pan-cytopenia, liver abnormalities, lymphadenopathy, coagulopathy and neurological involvement 14 , 15 . Overlapping clinical manifestations, mutual hyper-active innate responses as well as common serum and cellular biomarkers of CAPS and sJIA, particularly those with polycyclic and persistent disease course, can sometimes cause confusion for clinicians 3 , 16 . While the advance of molecular genetic testing was believed to provide strong support to the diagnosis, in a large French study covering 821 cases suspicious with CAPS, only 16% of the cases were identified with NLRP3 mutations 10 .…”

“…Many shared gene transcripts have been identified in patients with sJIA and CAPS 18 , 19 . Considerable body of works, additionally, have discussed about the gene expression profiling, cellular markers and serum biomarkers among the two diseases 16 . Limited data, however, were available directly comparing the markers between the two.…”