DM is a heterogeneous autoimmune disease with the anti-MDA5 + form exhibiting a characteristic rash and interstitial lung disease (ILD). The involvement of muscle tissue is rare, so that serum CK levels are usually normal. However, many patients develop rapidly progressive acute pulmonary failure, accounting for high mortality rates .
Neutrophils and lymphocytes play important roles in systemic autoimmune diseases with numbers and functions changing during disease progression. A component of the routine blood cell examination (RBC), NLR values have attracted increased attention in recent years for their utility in inflammatory and autoimmune disease. Previous work has indicated that NLR reflects disease activity in rheumatoid arthritis (RA)  and Bechet disease (BD) [12, 13], is a predictive marker for psoriatic arthritis (PsA)  and relates to the occurrence of lupus nephritis in systemic lupus erythematosus (SLE) [15, 16]. However, to the best of our knowledge, the relationship between NLR and MDA5 + DM has not been previously studied. Multiple indicators have been correlated with the prognosis of anti-MDA5 + DM, such as anti-MDA5 tilter , ferritin [4, 5, 17, 18], KL-6  and the proportion of CD4 + CXCR4 + T cells . The current study revealed elevated NLR to be an independent predictor for poor survival in anti-MDA5 + DM patients, in addition to LDH, CRP and other inflammatory indicators.
Knowledge regarding the pathogenic mechanisms of DM remains limited but it seems to disproportionately affect genetically susceptible populations and is triggered by infectious agents (viruses, picornaviruses, flaviviruses) . Neutrophils and lymphocytes produce a variety of cytokines and participate in DM pathogenesis. Vasculopathy is a well-established feature of MDA 5 + DM [21, 22]. Oxidative stress is involved in the pathophysiology of vascular inflammation in DM [23, 24]. Oxidative stress is associated with excessive inflammatory activity and NLR is a non-specific indicator of oxidative stress, reflecting the state of the body’s immune system [25, 26]. Antigen-stimulated responses in autoimmune diseases include production of reactive oxygen species and the resulting oxidative stress has an impact on disease progression, response to therapy and prognosis. NLR correlates with inflammatory factors, such as CRP, LDH and ferritin, and interplay of multiple factors, including pro- and anti-inflammatory factors, may be responsible for measured NLRs. NLR is also related to other pathological conditions, such as cancer [27–29], osteoarthritis [30, 31] and myocardial infarctions [32, 33].
NLR measurements are relatively inexpensive and easily incorporated into routine clinical practice. The predictive properties of NLR allow it to serve as a prognostic marker to aid clinical decision-making at an early stage of anti-MDA5 + DM disease. Anti-MDA5 + DM has a high mortality rate due to the common development of rapidly progressive interstitial lung disease (RP-ILD) which is difficult to treat, especially in combination with infection [34–36]. Seasonal and geographical variations in anti-MDA5 + DM suggest that infections, especially viruses, may be a predisposing factor, perhaps due to the induction of a cytokine storm [37, 38]. Viral RNA activates MDA5 in infected cells, leading to the production of type I interferon (IFN-I) and cytokines . Increased neutrophils during bacterial infection and decreased lymphocytes during viral infection contribute to high NLRs and dismal prognoses. Intervention at the early stage of anti-MDA5 + DM, when elevated NLRs may first be detected, may prevent or delay the development of cytokine storms and tissue damage.
Plasma LDH levels have previously been reported to be increased in RPILD and associated with high titers of anti-MDA5 antibody. A recent study has suggested that LDH > 335/L was an independent risk factor for poor prognosis in anti-MDA5 + DM . The current study found that serum LDH in patients with NLR > 4.86 was significantly higher than that in patients with NLR < 4.86 (Fig. 3A). This suggests that NLR measurements have a related function to those of LDH. However, LDH is released by many tissues, such as liver and kidney, and is greatly affected by CK levels. Therefore, NLR may prove to be a more appropriate indicator of inflammatory state in anti-MDA5 + DM.
Previous studies have identified HRCT score as an independent risk factor for poor prognosis in anti-MDA5 + DM  but the current studies do not replicate those results. This inconsistency may have arisen due to selection of first admission HRCT images from patients who have been hospitalized and scanned on several occasions.
Some DM patients deteriorate rapidly, often within the time-scale of 1 month. Therefore, early HRCT scores may not reliably indicate abnormality and vigilance is required to ensure repeated scans on follow-up.
We acknowledge several limitations to the current study. All data were derived from patients presenting at a single center. Moreover, NLR measured at initial presentation was included but not that after treatment, so that NLR changes could not be assessed. In addition, many factors, including treatment program and inflammatory severity, contribute to poor prognosis in anti-MDA5 + DM. Prognosis must be evaluated in combination with other indicators.