Clinical And Histopathological Features Of Necrotizing Myopathy With Anti-Signal Recognition Particle Antibodies

Objective To analyze myositis antoantibody profile of South Chinese patients; to observe and analyze clinical and histopathological features of necrotizing myopathy with anti-signal recognition particle(SRP) antibodies in South Chinese patients.Methods Sensitivity and specificity of myositis antoantibodies for idiopathic inflammatory myopathy(IIM) and incidences of each autoantibody in IIM were calculated based on 114 patients of our hospital from Dec 2012 to Feb 2014 with myositis autoantibody profile and confirmed diagnostic information. Clinical information of 26 IIM patients tested positive for anti-SRP antibodies was collected, who were followed up for their therapeutic effects and prognoses. Muscle biopsies were done on 22 patients, followed by hematoxylin eosin (HE) staining, immunohistochemical staining for CD4, CD 8, MHC-I, C5b-9 and KP-1. Clinical and histopathological features were compared among patients with acute onset(onset to maximum symptoms no longer than 6 months), subacute onset(onset to maximum symptoms between 6 months and 12 months) and with chronic onset(onset to maximum symptoms longer than 12 months), while histopathological features were compared between muscle samples from different phases of the disease course.Results The sensitivity and specificity of myositis autoantibodies for IIM were 74% and 88% respectively; additionally, the statistics were 52% and 94% for myositis specific antibodies(MSAs) and 52% and 94% for myositis associated antibodies(MAAs); anti-SRP antibody was the commonest MSA(28%), incidences of anti-Mi-2 and anti-Jo-1 were both 8%; anti-Ro-52 was the commonest MAA(41.9%). Female:male ratio of the 26 IIM patients with anti-SRP antibodies was 16:10. Mean onset age was 42.9±12.1, with the youngest 16 and oldest 62. Seasonal trends were not observed. Median onset to maximum symptom time span was 6.0 months(0.5-24.0 months). Median maximal CK level was 8704.0U/L(1349.0U/L-14620.0U/L). Mean worst MMT8 score was 53.3±9.9. Muscle atrophy(69.2%), dysphagia or dysarthria (46.2%), muscle pain(46.2%), interstitial lung disease(50%), ECG abnormalities(33.3%), UCG abnormalities(37.5%) were observed. Therapeutic regimens composed of more than one immunosuppressive agents were applied on 22 of the 26 patients, with 21 responsive,4 refractory and 1 developed steroids dependence. Therapeutic responses were better in females(p=0.014). Relapses and flares occurred in 8 patients(30.8%). Onset ages were older (P=0.011 and 0.024 respectively), maximum CK levels were lower (P=0.014 and 0.006 respectively) and worst MMT8 scores tended to be higher (P=0.074 and 0.155 respectively) in the chronic group than in the acute or subacute group. Patients in the subacute group were less responsive to therapies than patients in the acute group (P=0.005). Different phases of the disease course could be devided:phase I:(preclinical phase), phase Ⅱ(clinically onset phase), phase III(early treatment phase), phase IV(late treatment phase), phase V(remission phase). Varying degrees of scattered muscle fiber degeneration, necrosis and regeneration, muscle fiber size variation, endomysial connective tissue proliferation, inflammatory infiltration, MHC-I upregulation and C5b-9 deposition could be observed in most patients. Regeneration, muscle fiber size variation, endomysial connective tissue proliferation, C5b-9 deposition along the non-necrotic fiber sarcolemma were more pronounced in muscle samples from phase III and IV compared with phase I and II(p<0.05). Necrosis tended to be milder(p=0.385) and MHC-Ⅰ upregulation tended to be severer(p=0.093) in muscle samples from phase III and IV. Follow-up of one patient’s anti-SRP antibody from phase II, phase IV and phase V of the disease course showed constant chromaticity of 3+.Conclusions Myositis autoantibody tests have high sensitivity and specificity for South Chinese IIM patients. The incidence of anti-SRP antibody in South Chinese IIM patients is 28%. Main clinical features of necrotizing myopathy with anti-SRP antibodies in South Chinese patients are rapidly progressive and severe proximal muscle weakness with marked CK elevation. Muscle atrophy, weight loss and bulber signs are also distinct features. Most patients require 2-3 agents to control their disease. Responses can usually be achieved but with a high frequency of relapse and flare. Therapeutic responses are better in females. Onset ages are older and weaknesses and CK elevations are milder in the chronic group. Satisfying therapeutic responses are less frequent in the subacute group. Histopathological features are varying degrees of scattered muscle fiber degeneration, necrosis and regeneration, muscle fiber size variation, endomysial connective tissue proliferation, inflammatory infiltration, MHC-I upregulation and C5b-9 deposition. As disease progresses, regeneration, muscle fiber size variation, endomysial connective tissue proliferation, MHC-I upregulation and C5b-9 deposition along the non-necrotic fiber sarcolemma turn more prominent, while muscle fiber necrosis turns milder, which might be the pathological basis of some clinical phenomena of certain phases.