Correlation of serum neopterin concentrations with disease activity in juvenile dermatomyositis.

Objective Muscle enzyme levels are insensitive markers of disease activity in juvenile and adult dermatomyositis (DM), especially during the active treatment phase. To improve our ability to monitor DM disease activity longitudinally, especially in the presence of immune modulating agents, we prospectively evaluated whether IFN-dependent peripheral blood gene and chemokine signatures could serve as sensitive and responsive biomarkers for change in disease activity in adult and juvenile DM. Methods Peripheral blood and clinical data were collected from 51 juvenile and adult DM subjects prospectively over 2 study visits. Disease activity measures, whole-blood type I IFN gene and chemokine score were collected. We also measured serum levels of other pro-inflammatory cytokines, including IL-6. Results Changes in juvenile and adult DM global disease activity correlated positively and significantly with changes in the type I IFN gene score before (r=0.33, p=0.023) and IFN chemokine score before and after adjustment for medication use (r=0.53, p<0.001 and r=0.50, p=<0.001). Changes in muscle and extramuscular VAS subscales positively correlated with change in IFN gene and chemokine score (p=0.002). Serum levels of IL-6, IL-8 and TNFα were positively correlated with changes in global, muscle and extra-muscular VAS before and after adjustment for medications (p<0.05). Conclusion Our findings suggest that changes in type I IFN gene and chemokine scores as well as levels of IL-6, IL-8 and TNFα may serve as sensitive and responsive longitudinal biomarkers of change in disease activity in juvenile and adult DM, even in the presence of immunosuppressant use.

Section: Discussionmentioning

confidence: 99%

Changes in novel biomarkers of disease activity in juvenile and adult dermatomyositis are sensitive biomarkers of disease course

Reed¹,

Peterson²,

Bilgiç³

et al. 2012

“…Standard determinations of the muscle-derived enzymes creatine phosphokinase (CPK), aldolase, aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), and lactic acid dehydrogenase (LDH), obtained at diagnosis, are presented in Table 1 (see Results). At CMMC, other special tests were performed to assess the patient's response to therapy; these were measurement of neopterin, a T cell-dependent macrophage-derived product (Immunotest Neopterin; Henning Berlin, DRG International, Mountainside, NJ) (19,20), and flow cytometric analysis of PBMC for the percentage of CD19ϩ B cells (21,22). In addition, values for the von Willebrand factor antigen (vWF: Ag, by quantitative immunoelectrophoresis and Laurell's test) (23) were obtained as described in other studies of juvenile DM (24)(25)(26).…”

Section: Methodsmentioning

confidence: 99%

TNFα-308A allele in juvenile dermatomyositis: Association with increased production of tumor necrosis factor α, disease duration, and pathologic calcifications

Pachman

Liotta-Davis

Hong

et al. 2000

225

123

“…Disease duration at the time of sampling was defined as the time from the first disease-related symptom (skin rash or muscle weakness). Active myositis at time of sampling was defined on the basis of decreased muscle strength, determined using a standard muscle strength score (25). All patients with normal muscle strength also had muscle enzyme levels that were less than twice the upper limit of the normal range.…”

Section: Methodsmentioning

confidence: 99%

Self epitopes shared between human skeletal myosin and Streptococcus pyogenes M5 protein are targets of immune responses in active juvenile dermatomyositis

Massa

Costouros

Mazzoli

et al. 2002

Objective. To identify self T cell epitopes associated with proinflammatory immune responses and clinically active juvenile dermatomyositis (juvenile DM). The target of our search for relevant epitopes was represented by amino acid sequences shared between human skeletal myosin and Streptococcus pyogenes M5 protein. The long-term objective of the project is to identify suitable targets for immunotherapy of the disease.Methods. We used computerized algorithms to identify putative agretopes on both the human myosin and Streptococcus M5 proteins. Direct binding assays for homolog peptides were used to confirm such predictions. Antigenicity and functional cross-reactivity were evaluated by cytotoxicity assays and by measurement of cytokine levels. Specific T cells were isolated by T cell capture, and T cell receptor (TCR) V ␤ gene usage was identified by reverse transcriptase-polymerase chain reaction.Results. We identified peptides that are targets of disease-specific cytotoxic T cell responses. T cell reactivity against the self peptides correlates with clinical signs of early, active myositis. Such reactivity is accompanied by production of proinflammatory cytokines, which may contribute to the damage. T cell crossrecognition of bacterial and human homologs was shown functionally as well as by sorting peptide-specific T cells and identifying oligoclonal and largely overlapping TCR V ␤ gene usage.Conclusion. These findings represent the first identification of a self epitope in juvenile DM, providing a potential candidate for antigen-specific immune therapy.