Background/Purpose: Perturbations in peripheral blood lymphocyte (PBL) subsets in juvenile dermatomyositis (JDM) are variably and inconsistently reported in active and inactive disease. Decreased PBL CD8+ T cells and increased CD4+ T cells, and CD19+ B cells have been correlated with disease activity in JDM. Increased numbers of CD56+ NK cells have been found in inflamed muscle of JDM patients. Untreated JDM patients have decreased levels of CD3-CD16+, CD54+ (ICAM-1), CD56+ (NK) and CD3+CD8+ T suppressor cells, suggesting that they are contributing to pathogenesis. We sought to determine the subsets of PBLs which correspond with improved disease activity in JDM.

Methods: Peripheral blood mononuclear cell (PBMC ) samples from 24 patients with definite JDM were collected between 2007-2011 in two visits, 3-6 months apart. Frozen PBMC samples were analyzed using fluorescence activated cell sorting and flow cytometric analysis. Childhood myositis activity tools validated by the International Myositis Assessment & Clinical Studies Group (IMACS) for the assessment of disease activity were used including visual analog scores (VAS). Spearman correlation methods were used.

Results: The mean age was 9.5 (min: 3, max: 19) years and 15 (63%) were female. The figure shows significant correlations between the change in VAS scores between visits and change in percentage of lymphocyte subsets. The change in the percentage of CD3+ CD69+ T cells was positively correlated with the change in global VAS (p=0.037). The change in the percentage of HLA-DR- CD11c+ myeloid dendritic cells (mDCs) was positively correlated with change in extramuscular VAS (p = 0.040).  The change in the percentage of HLA-DR- CD123+ plasmacytoid dendritic cells (pDCs) cells negatively correlated with change in muscle VAS (p=0.028). Although the results did not reach statistical significance, some trends were noted. The change in the percentage of HLA-DR- CD11c+ mDCs was positively correlated to the change in muscle VAS (p=0.08) and global VAS (p=0.08). The change in the percentage of CD16-CD56+ NK cells and of HLA-DR- CD86+ mDCs was positively correlated with the change in extramuscular VAS (p=0.08, and p=0.09, respectively). In addition, the change in percentage of CD16+ CD56- NK cells was inversely correlated to the change in global VAS (p=0.09).

Conclusion: This is the first prospective study in JDM patients to identify the relationship of disease activity with PBL subsets: CD3+ CD69+ T cells, HLA-DR- CD11c+ mDCs, and HLA-DR- CD123+ pDCs. Additionally, our findings suggest that NK cells do not correlate with disease activity level in JDM. There is a trend toward decreased levels of CD3-CD16-CD56+ NK cells with decreased extramuscular VAS, and increased CD 16+CD56- NK cells with decreased global VAS.

Figure: Change between visits in peripheral lymphocyte cell subsets vs. change in VAS scores.