OP0055 - Clinical associations of Autoantibodies to a P155/140 KDA Doublet in Adult and Juvenile Dermatomyositis
Authors: H. Gunawardena 1, J. North 2, L.R. Wedderburn 3, J.E. Davidson 4, Z.E. Betteridge 2, J. Dunphy 5, H. Chinoy 6, R.G. Cooper 6, N.J. McHugh 1. 1Rheumatology, Royal National Hospital for Rheumatic Diseases, 2School for Health, University of Bath, Bath, 3Rheumatology, Institute for Child Health, University College London, London, 4Rheumatology, Royal Hospital for Sick Children, Glasgow, 5Bath Institute for Rheumatic Diseases, Royal National Hospital for Rheumatic Diseases, Bath, 6Rheumatic Diseases Centre, Hope Hospital, Salford, United Kingdom
Background:
Dermatomyositis (DM) in adults and children is characterized by a variable degree of myositis, cutaneous lesions and, occasionally, internal organ involvement. There are however specific differences; the association with malignancy in adult DM is well recognized but this is rare in juvenile DM (JDM), whereas ulceration and calcinosis is more frequent. Identification of myositis specific autoantibodies (MSA) in adults can define homogeneous clinical subsets, however MSA in JDM are not well characterized. There are reports of autoantibodies to 155/140 kDa proteins (anti-p155/140) in both adult DM and JDM , thus this area is of major interest.
Objective:
This study was conducted to establish the frequency and clinical associations of anti-p155/140 in DM.
Methods:
Sera from 116 children (JDM National Registry and Repository) and from 20 adults with DM (Royal National Hospital for Rheumatic Diseases) were screened by indirect immunofluorescence (IF) and radioimmunoprecipitation (IPP) of [35S]-methionine labelled K562 cells. Immunodepletion was used to establish whether the p155/140 autoantigen recognized by adult sera was the same as that recognized by JDM sera. Control sera were used from adults with PM, SSc, SLE, and healthy controls.
Clinical features were compared using SPSS version 12.
Results:
Anti-p155/140 autoantibodies were detected in six adult DM (30%) and 27 JDM (23%) patients using IPP associated with a non-specific nuclear pattern on IF. All control sera were negative for anti-p155/140. Immunodepletion confirmed the 155/140 kDa proteins recognized by adult DM and JDM were the same targets.
Adult DM patients with anti-p155/140 had more skin disease; in particular 83% had a V-sign and Shawl-sign rash compared to 21% of anti-p155/140 negative adults (p<0.05). Heliotrope and Gottron's rash were more frequent in anti-p155/140 positive adults; 83% vs. 36% and 100% vs. 57% respectively (p=ns). Malignancy was found in 50% of anti-p155/140 adults whereas no anti-p155/140 negative adults had cancer (p<0.05). There was a higher frequency of males in anti-p155/140 positive JDM group (p<0.05) and overall more cutaneous lesions compared to anti-p155/140 negative JDM; including Gottron's papules 100% vs. 76% (p<0.01), ulceration 52% vs. 23% (p<0.01) and edema 63% vs. 34% (p<0.05). Anti-p155/140 positive JDM also had a wider distribution of rash, periorbitally (p<0.05) and over the joints (p<0.01).
Conclusion:
Anti-p155/140 is detected in both adult and juvenile DM. Identification of this novel MSA may define a homogeneous subset of patients with more severe skin disease and help predict clinical course. It remains unclear why a tumor associated autoantigen in adult DM is recognized in JDM and further characterization of this target is required.
Comment:
The frequency and clinical associations of anti p-155/140 is of interest since initial description by Targoff and colleagues A & R 20007 Jan). This study specifically looked at these associations in children and adults with DM. There is debate as to whether JDM and the aduklt version of DM share the same pathogenesis. Clinical differences include the rare development of clcinosis in adults with DM compared to children with JDM and the development of mesenteric vasculaitis in JDM with a rare occurrence in adults with adult DM. Likewise, children with JDM do not seem to have the same risk for malignancy as adults with DM. This study demonstrates that the anti p-155/140 is found in JDM and may be associated with more severe skin disease. Why a cancer- associated autoanigen is found in patients with JDM is not understood. Perhaps it is a marker for more severe skin disease in both adults and children and a marker of malignancy in adults only.