Background/Purpose: Juvenile Dermatomyositis (JDM) is a rare pediatric autoimmune disease characterized by muscle and skin inflammation. The Pathophysiology of JDM is complex; it involves both adaptive and innate immune system dysregulation. The increase in type I and type II interferon signature is well documented in JDM patients. IFN-α has been shown to enhance Natural Killer (NK) cell degranulation and inflammatory cytokine production. However, information about how NK cells contribute to the pathophysiology in JDM patients is lacking. This study aims to evaluate the changes in the NK cell count and its correlation with various disease activity markers.

Methods: This IRB-approved retrospective study was conducted at the Ann and Robert H. Lurie Children’s Hospital of Chicago. 135 subjects (76% female, 74% white, 18.5 % Hispanic, 3% black) were included in this study. Clinical and laboratory variables, including age, race, gender, MSA, Disease Activity Scores (DAS skin, muscle, total), nailfold capillary count, neopterin, and muscle enzymes, were obtained from the Lurie Children’s Juvenile Myositis Registry REDCap database. All subjects had flow cytometry (CD3, CD4, CD8, CD16/56, CD19, and HLA-Dr) before receiving treatment for JDM. To identify which NK cell subtype (CD56dim, CD56 bright) is affected in JDM, another flow cytometry was done with CD16 and CD56 on different fluorochromes in a smaller subset of the untreated JDM and control subjects.

Results: 57% of the untreated JDM children had low NK cells. Those with low NK cell count had more active disease with mean DAS-total 11.6 vs 9.6 (p= 0.001), DAS-muscle 5.8 vs 3.9 (p< 0.001), neopterin levels 22.1 vs 15.5 (p=0.003). Muscle enzymes were higher in the NK low groups as following: CPK 2733 vs 474 (p= 0.025), AST 147 vs 54(p= 0.003), LDH 491 vs 348(p= 0.006), Aldolase 23 vs 11(p= 0.013). There was no significant difference in the DAS-skin or nailfold capillary count between NK low group or normal. Among the different MSAs groups, the anti-MJ group has the Lowest mean NK cell count at 105+/- 52, and the anti P155/140 group has the highest level at 196 +/- 161; however, the difference was not statistically significant. Then we examined the NK cell subset in six JDM with low NK cells, three JDM with normal NK, and three healthy controls. CD56 dim NK cell percentage was significantly lower in NK low group than in control (0.55 % vs 4.6 % P< 0.001), whereas CD56 bright percentage did not differ significantly ( 0.45% vs 0.83% P=0.199).

Conclusion: Significant percentage of JDM children have low NK cells before treatment, suggesting that NK cells are likely to be contributing to the disease pathophysiology. Furthermore, JDM subjects with low NK cells show higher disease activity, especially in the muscle weakness and elevated muscle enzymes. Most of the NK cell count reduction is caused by the decreased number of the CD56 dim population, which is more cytotoxic with high perforin expression. Further studies of JDM muscle biopsies are in progress to determine if the CD56 dim NK cell counts are decreased in peripheral blood due to muscle infiltration.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/decreased-peripheral-blood-natural-killer-cell-count-in-untreated-juvenile-dermatomyositis-is-associated-with-muscle-weakness/