CIDP is considered an acquired inflammatory disease of the peripheral nerves. About two-thirds of patients experienced relapse and one-third experienced progression (stable or stepwise)[19].Pathologic markers of CIDP are segmental demyelination and remyelination, as well as endoneural mononuclear infiltration[20].During the active stage of CIDP, peripheral nerve biopsy often reveals inflammatory infiltration of T cells and macrophage-mediated demyelination of the intima of the nerve, suggesting that T lymphocytes, macrophages, and their cytokines play a key role in the pathogenesis of the disease[21].
The blood-nerve barrier (BNB) is a dynamic andeffectiveinterface between the endoneurial microenvironment and the surrounding extracellular space or blood. Because BNB tightly seals the healthy peripheral nervous system (PNS) to prevent random migration of cells tothe PNS, the peripheral nerves are under constant immune monitoring by T, B cells and macrophages[22].Thoseautoimmune disorders of PNS including CIDP follows BNB impairment. The breakdown of the BNB has been considered an important role in disease pathogenesis[23].Local activation of cell-adhesion molecules, inflammatory cytokines, matrix metalloproteinases, or other inflammatory substances may disrupt the barrier, leading to the development and further deterioration of peripheral neuropathy,and hematogenous leukocytes were actively involved in axonal degeneration, demyelination, or both, with resultant motor and sensory disturbances[24].Immune-mediated demyelination initially affects distal nerve endings/roots, but with upregulation of pro-inflammatory cytokines (e.g., interleukin, tumor necrosis factor, interferon) and complement, the blood-nerve barrier is disrupted and demyelination gradually extends to the nerve stem.Pro-inflammatory cytokines are mainly induced by lymphocytes, neutrophils, macrophages and monocytes[25, 26].
The inflammatory markers such as white cell counts (WBC), C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR), or there components have pivotal role in Neuroimmune disease development and progression. White blood cells, especially neutrophils are the primary response to systemic inflammation.CRPis mainly classed as one of the most sensitive acute phase reactants buta nonspecific indicator of inflammation.ESRcan be increased in infection, inflammation, trauma, tumor and other diseases.Albumin is made in the liver and acts as a nourishing cell.Decreased serum albumin level is also associated with increased systemic inflammatory load[27].Globulin is also useful in immune responses.
The albumin/globulin ratio (A/G) is a more accurate indicator of nutritional status and systemic inflammatory response than a single.The decrease of albumin or the increase of globulin are the main reasons for the low A/G,which often suggestive chronic inflammatory and immune diseases.Furthermore,low A/G was significantly correlated with low hemoglobin level[28, 29].
In our study, we assessed the diagnostic accuracy of hematologic parameters to determine the disease activity in CIDP patients, since biomarkers are available and universally monitored in clinical practice.
Monocytes are the largest white blood cells that play a crucial part in the defense system.Studies have shown that monocytes are significantly pluripotent in different inflammatory environments[30].Compared with other blood cells, monocytes contain more non-specific lipases and have stronger phagocytosis.When inflammation or other immune diseases occur in the body, the number of total monocytes can be changed[31]. Similarly,Lymphocyte have a sensitive immune response in inflammation.Therefore, the examination of monocyte and lymphocyte counts have become an important method for auxiliary diagnosis[4].Besides, Platelets are also a component of the immune system and play a directrolein regulating and inducing tissue damage and pathogen responses.They contain and release or re-produce a large number of immune molecules that directly affect the development and outcome of inflammatory diseases[32].Morerecently, PLR, NLR, and LMR values have been often used as prognostic indicators of systemic inflammation,immunological diseases and malignancies[33-37].
In previous studies, LMR has been widely used due to its of measurement,low price and strong practicability. In recent years, LMR has attracted extensiveattention in the diagnosis and/or prognosis of cancers,various immunological diseases,even cardiovascular and cerebrovascular diseases.Goto et al.had reported that LMR might be a useful prognostic indicator for breast cancer patients. Accordingly, low LMR was an independent risk factor for disease-free survival rate[38].Wang et al. suggested that LMR may be an important inflammatory marker for the identification of axial spondyloarthritis(SpA) and assessment of disease activity and X-ray staging of sacroilitis[39].In short,LMR represents a balance between the lymphocyte and monocyte levels of the patient.Low LMR represents a decreased lymphocyte count and an increased monocyte count in the blood,leading to a weakened immune response and a strong inflammatory reaction.
The main findings of this study were as follows: (1)LMR was lowerin CIDP patients vs.HCssubjects, and the differences were significant. Active disease CIDP patients showed lower LMR levels compared to the remission group;(2) LMR was positively correlated with parameters ofHb, RBC, and A/G (P<0.05),andnegatively correlated withNLR, PLR, RDW;(3) ROC curve analysis showed that LMR had a high diagnostic value for CIDP witha sensitivity of 77.78% and a specificity of 75%.The sensitivity was strong in the combined diagnostic AUC of ESR, A/G, but the specificitywas weak.
To the best of our knowledge,our study is the first attempt to assess the role of LMR in CIDP patients. This comprehensive study demonstrated a significant association between LMR and CIDP. Furthermore, multivariate analysis showed that LMR was significantly reduced in patients with active CIDP, thoughweak sensitivity and specificity. It showed that LMR had been identified as a diagnostic marker of activity and severity in CIDP disease. Moreover, the LMR (based on ESR and A/G) was shown to be of prognostic value in predicting outcomes.
The simple correlation analysis showed positive associationswere found between LMR and Hb (Hemoglobin), RBC (Red blood cells), and A/G (Albumin/globulin ratio), whereas negative correlations were observed between LMR and NLR, PLR, RDW (Red cell distribution width) (P<0.05), indicating the correlation between LMR and systemic severity index.
Nevertheless, the thesis remains hypothetical and should be addressed in further studies. Firstly, this study was a retrospective, single-center research with a relatively small sample size.Therefore,we plan to include more CIDP patients in a multi-center randomized study for verification, so as to obtain more definite results. Secondly, LMR is a nonspecific marker of inflammation that is affected by inflammation, immune system diseases and other tumors in patients.Therefore, further prospective validation is needed to support the use of LMR in CIDP prognostic and predictive models.