Clinical,Pathological And Radiological Features And Prognosis Of 52 Patients With Anti-SRP IgG Positive Immune-mediate Necrotizing Myopathy

Background and objectiveImmune-mediate necrotizing myopathy(IMNM)is a subtype of idiopathic inflammatory myopathies(IIMs).Clinically,muscle weakness is generally rapid progressive and severe in INMN patients,accompanied with increased serum creatine kinase(CK)levels.Muscle biopsies often show an active myopathy,including numerous scattered fiber necrosis and regeneration,with no or slight inflammatory infiltration.Prednisone monotherapy is insufficient to control disease in most patients.Three serologically-defined subtypes of IMNM are presently recognized:signal recognition particle(SRP)antibody-positive IMNM,3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMGCR)antibody-positive IMNM and seronegative IMNM.Given that there are differences in many studies on SRP antibody-positive IMNM worldwide,and no large cohort of cases have been reported in China,we aim to systematically summarize the clinical characteristics,muscle imaging manifestations,pathological findings,treatment and prognosis of SRP antibody positive IMNM in our neuromuscular center.MethodsThis was a single-center retrospective observational study on 52 SRP antibody-positive IMNM patients collected in Qilu hospital of Shandong University from April,2005 to May,2021.All enrolled patients were met the criteria of European Neuromuscular Center(ENMC),and were confirmed by myositis antibody detections(Immunoblotting,western blotting or enzyme-linked immunosorbent assay).Clinical features,muscle imaging findings,muscle pathology,treatment and prognosis of 52 cases of SRP antibody-positive IMNM were comprehensively summarized.Results1.Clinical characteristics:There were 33 females and 19 males among 52 SRP antibody-positive IMNM patients.The patients’average age was 48.0±12.3 years,ranging from 11 to 72 years old.The maximum value of CK was 15754.0 U/L,the minimum value of CK was 1400.0 U/L,the median value of CK was 5365.0 U/L.All patients presented proximal muscle weakness,42 patients(80.8%)experienced neck weakness,and dysphagia was present in 30 patients(57.7%).2.Imaging characteristics:Magnetic resonance imaging(MRI)of thigh muscles was performed in 15 patients.Among them,9 patients(60.0%)showed moderate fatty infiltration of gluteus maximus muscle,and 8 patients(53.3%)showed moderate fatty infiltration of semimembranosus,semitendinosus and biceps femoris long head,7 patients(46.7%)showed moderate fatty infiltration of adductor magnus.Severe edema was found in adductor magnus muscle in 12 patients(80.0%)and semimembranosus muscle in 11 patients(73.3%).Nine patients(60.0%)showed severe edema of biceps femoris long head.There was no correlation between the score of fatty infiltration or oedema of individual thigh muscle and disease duration(P>0.05).There was a statistically significant correlation between the cumulative score of thigh muscles oedema and CK levels(r=0.713,P=0.003).In 7 patients,MRI of the shank muscles was performed.Four patients(57.1%)showed severe edema in soleus and 2 patients(28.6%)showed moderate fatty infiltration in soleus.3.Pathological features:All 52 patients showed varying degrees of scattered muscle fiber necrosis and regeneration on muscle biopsies.Obvious scattered CD3 positive T-lymphocytes were found within endomysium on muscle biopsies of 13 patients(29.5%),with foci of lymphocytes infiltration found only in 4 patients(9.1%).Positive expression of major histocompatibility complex class Ⅰ(MHC-I)antibody was observed in 36 patients(69.2%).Diffusely MHC-I expression on sarcolemma of non-necrotic fibers were found in 11 patients(21.2%),while nonspecific and weak MHC-I expression were detected in 25 patients(48.1%).Expression of membrane attack complex(MAC)were found in 23 patients(44.2%),with MAC deposition on sarcolemma of non-necrotic fibers in 20 patients(38.5%)and on the capillaries in 3 patients(5.8%).4.Treatment and prognosis:Among the 52 patients,47 patients were systematically followed up while 5 were lost to follow-up.The longest follow-up time of the remaining 45 patients was 197 months,the shortest was 6 months,and the median follow-up time was 43 months,except 2 patients who died respectively 1 month and 1.3 months after initial treatment.Among the 47 follow-up patients,38(80.9%)were treated with glucocorticoids combined with immunosuppressant and/or immunoglobulin,and only 9(19.1%)were treated with glucocorticoids alone.Twenty-one patients(44.7%)relapsed and 35(74.5%)had a favorable outcome.Six patients(12.8%)died,including 4 cases due to severe muscle weakness,1 due to myocardial infarction,and 1 highly suspected of intestinal malignant tumor.Conclusions1.SRP antibody-positive IMNM mainly manifested as proximal limb weakness with significantly increased CK level.In addition,neck muscle weakness and dysphagia are also prominent clinical symptoms.2.MRI reveals gluteus maximus,adductor magnus,posterior thigh muscles(semimembranosus,semitendinosus and biceps femoris long head)and posterior shank muscles(soleus)are frequently affected.MRI reveals fatty infiltration and oedema in the muscles of all patients,and oedema is more pronounced than fatty infiltration in these patients.There was no correlation between the score of fatty infiltration or oedema of individual thigh muscle and disease duration.However,there was a statistically significant positive correlation between the cumulative score of thigh muscles oedema and CK levels.3.The main pathological findings of muscle biopsies show apparent fiber necrosis and regeneration,accompanied by no or slight inflammation.The deposition of MAC often detected on sarcolemma of non-necrotic fibers,while MHC-I is often expressed nonspecifically on sarcolemma of non-necrotic fibers.4.SRP antibody-positive IMNM has a high of frequency of relapse,a combination of corticosteroid and immunosuppressive agents and/or immunoglobulin could achieve a good response.