Children with JDM who demonstrate oligoclonal B cell expansion (CJ:KREC ≥ 8) prior to the use of Rituximab have more favorable clinical outcomes after Rituximab therapy. If this finding is confirmed by subsequent studies, the CJ:KREC ratio may serve as a selection criterion for Rituximab therapy in JDM patients. Additionally, qPCR analysis of Coding joint (CJ) and KREC DNA can replace more expensive laboratory evaluations (such as flow cytometry of B cells and B cell subsets), and can be utilized to predict response to therapy and monitor B cell reconstitution. This evaluation could be utilized in a wide variety of clinical settings including international and/ or limited health resource settings, to help predict response to therapy and guide medication management when flow cytometric measures are not available.

Prior research has attempted to identify predictors of clinical improvement in myositis patients treated with Rituximab. Anti-synthetase and anti-Mi-2 MSAs in JDM appear to be associated with lower disease damage and increased clinical improvement in patients with refractory myositis [7]. According to current guidelines, Rituximab is reserved for JDM patients who have failed first-line therapy [6, 7]. Precision medicine approaches to complex patients with refractory JDM are needed, and we propose that the CJ:KREC ratio can assist in the identification of JDM patients who are most likely to respond to B cell depleting therapy.

Serum soluble BAFF level generally increases after Rituximab due to B cell depletion as a mechanism to promote B cell count recovery. However, in patients with poor B cell depletion, there is only a minor increase in serum BAFF level after treatment. Patients with X- linked Agammaglobulinemia (who have absent B cells due to a genetic defect) have significantly higher soluble BAFF concentrations compared to healthy controls (p < 0.001) [14]. Our data, taken together with prior research, suggests that the more significant the B cell deficit, either iatrogenically induced or due to an inherited B cell deficiency, the higher the resulting soluble BAFF level. Further research is required to understand if this increase in serum BAFF level after B cell depletion contributes to disease flare post-Rituximab, and if so, it could potentially provide an additional therapeutic target in JDM. Belimumab is a humanized IgG1γ antibody directed against BAFF, currently approved for the treatment of systemic lupus erythematosus (SLE). Directed therapies such as this could be important disease modulators in other autoimmune diseases such as JDM.

The limitations of this study include the small numbers of subjects, which requires validation in additional cohorts. Additionally, this was a single-center retrospective review, thus its generalizability may be limited. We did not assess adult myositis patients, thus age differences in response to Rituximab therapy cannot be extrapolated from this work. Finally, there is no commercially available predetermined standard sample to calibrate KREC and JC RT-PCR assay. Creating such a sample will facilitate wider adoption of this technology and assure test reliability between different laboratories.

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