Calcinosis in juvenile dermatomyositis: a possible role for the vitamin K-dependent protein matrix Gla protein

Objectives. The aims of the present study were to investigatewhether the calcification inhibitor matrix Gla protein (MGP)is expressed in muscle biopsies of patients with juvenile dermatomyositis(JDM), and whether different forms of MGP are differentiallyexpressed in JDM patients with and without subcutaneous calcifications. Methods. Muscle tissue from six JDM patients (three withoutcalcinosis, two with calcinosis and one recently diagnosed patient),four patients with muscular dystrophy, three patients with IBMand five normal histological control subjects was used for immunohistochemistrystaining using novel antibodies to different conformations ofMGP. Results. In the JDM patients, all forms of MGP [non-carboxylatedMGP (ucMGP), carboxylated MGP (cMGP), non-phosphorylated MGP(serMGP) and phosphorylated MGP (pserMGP)] were more intenselystained in the perifascicular compared with the central musclefibres. In addition, these MGP species were demonstrated inthe pathological muscle fibres of IBM and dystrophy patients,but hardly in normal histological muscle tissue. In JDM patientswith calcifications, only pserMGP was increased compared withthose without calcifications. All forms of MGP were also foundin various staining intensities in the microvasculature andmacrophages of normal histological and disease biopsies. Conclusions. MGP was expressed at the site of muscle damagein JDM patients as well as in patients with muscular dystrophyand IBM. The difference in staining intensity of pserMGP appearedto distinguish between JDM patients with and without calcifications,whereas cMGP, the other functional form, was equally expressed. KEY WORDS: Vitamin K-dependent proteins, Matrix Gla protein, Juvenile dermatomyositis, Immunohistochemistry, MuscleSubmitted 23 July 2007; revised version accepted 6 December 2007.