The Assessment Of Cutaneous Lesions And Detection Of Serum Biomarkers In Dermatomyositis/Clinically Amyopathic Dermatomyositis

Objective: To evaluate the validity of three kinds of cutaneous scoring methods and to evaluate the clinical significance of skin lesions in dermatomyositis and clinically amyopathic dermatomyostis(DM/CADM).To detect serum biomarkers such as anti-MDA5(Melanoma differentiation associated gene 5)antibody and cytokines/chemokines and to evaluate their correlation with disease activitiy and prognosis.Methods: Cutaneous dermatomyositis disease area and severity(CDASI),Dermatomyositis skin severity index(DSSI),Cutaneous assessment tool(CAT)and Physician global assessment(PGA)were used to evaluated skin eruptions of 40 patients with dermatomyositis.Serum anti-MDA5 antibody was detected by ELISA and Western blot using recombinant MDA5 protein.The concentration of serum MDA5 protein was detected by Western blot.Expression of MDA5 protein in skin lesions was detected by immunohistochemistry.Serum levels of 14 kinds of cytokines / chemokines(including IL-2,IL-4,IL-6,IL-10,IL-17 A,IL-18,TNF,IFN-?,IFN-?,IL-8,CCL-5,CXCL-9,CCL-2 and CXCL-10)were detected by CBA or ELISA in 40 patients with DM/CADM and 16 healthy controls.Results: The three kinds of objective scoring methods could effectively evaluate the severity of skin lesions in DM/CADM,especially CDASI.The activity score of CDASI and CAT and the score of DSSI were significantly correlated with serum level of LDH,all P <0.05.The sensitivity of ELISA using recombinant MDA5 protein was 100% and the specificity was 93.1%.In addition,the sensitivity to acute / subacute pulmonary interstitial disease(A/SIP)was 84.6% and the specificity was 92.6% when serum anti-MDA5 antibody level was above 155.36 U/ml.The expression of MDA5 protein in the serum of DM/CADM patients with MDA5 antibody was decreased and the expression of MDA5 in skin lesion(ulcer)was increased.Serum levels of IL-6,IL-10,IL-18,IFN-?,CXCL-9,CCL-2 and CXCL-10 in DM/CADM patients were significantly higher than those in healthy controls,all P <0.001.Serum level of IL-18 were significantly higher in patients with ulcerative Gottron rash(603.7±170.3pg/ml)than in Gottorn rash patients without ulceration(468.7±182.0 pg/ml),P =0.021.The levels of serum IFN-? and CXCL-10 were significantly correlated with the activity score of CDASI and CAT and the score of DSSI,all P <0.05.Serum levels of IL-6 and IL-18 were significantly correlated with serum levels of anti-MDA5 antibody,both P <0.01.The levels of serum IL-6,IL-10,IL-18,IFN-?,anti-MDA5 antibody were significantly higher and complement 3 were significantly lower in patients with A/SIP than patients without A/SIP,all P <0.05.Conclusions: CDASI is the most effective method to evaluate skin lesions.Serum LDH may reflect the severity of skin lesions.MDA5 protein expressed in the vascular wall of the lesion may lead to the production of MDA5 antibody and bind to the antibody.The level of serum IL-18 is significantly associated with anti-MDA5 antibody,skin ulcer and A/SIP,which may be a key cytokine of MDA5 antibody-related DM/ CADM,may provide clues to explain the pathogenesis of MDA5 antibody.Complement 3 may be involved in the development of A/SIP.