Histological and molecular alterations in inflammatory myopathies [Alteraciones histol�gicas y moleculares en miopat�as inflamatorias]

The histological findings in muscle biopsies of inflammatory myopathies have been divided into 2 groups: A) Endomisial infiltrates mainly by T CD8+, CD4+ and macrophages and B) Perivascular infiltrates by CD4+, B cells and macrophages. The first kind of infiltrate suggests an immune reaction against muscle fibers very common in PM and inclusion body myositis, On the other hand the perivascular infiltrate is a hallmark of DM. It has ben shown that autoantigens related with myopathies such as Mi-2, Jo-1, OJ, PL12, Ku, PM/Scl are able to suffer proteolytic cleavage by granzyme B and other stimulus induced by cytotoxic T cells. In this chapter we will review the histological and molecular findings of inflammatory myopathies but we will also discuss a special group of myopathies related to the presence of antibodies against the SRP complex, in particular the SRP72 and SRP54 antibodies, which are associated with a poor prognosis and clinical outcome and present an inadequate response to conventional treatment. � 2009 Elsevier Espa�a, S.L. All rights reserved

[Histological and molecular alterations in inflammatory myopathies]

The histological findings in muscle biopsies of inflammatory myopathies have been divided into 2 groups: A) Endomisial infiltrates mainly by T CD8+, CD4+ and macrophages and B) Perivascular infiltrates by CD4+, B cells and macrophages. The first kind of infiltrate suggests an immune reaction against muscle fibers very common in PM and inclusion body myositis, On the other hand the perivascular infiltrate is a hallmark of DM. It has ben shown that autoantigens related with myopathies such as Mi-2, Jo-1, OJ, PL12, Ku, PM/Scl are able to suffer proteolytic cleavage by granzyme B and other stimulus induced by cytotoxic T cells. In this chapter we will review the histological and molecular findings of inflammatory myopathies but we will also discuss a special group of myopathies related to the presence of antibodies against the SRP complex, in particular the SRP72 and SRP54 antibodies, which are associated with a poor prognosis and clinical outcome and present an inadequate response to conventional treatment.Copyright ?� 2009 Elsevier Espana, S.L. All rights reserved

Genotoxic evaluation of pirfenidone using erythrocyte rodent micronucleus assay

Background: We describe a family with a 7-year-old proband case diagnosed with systemic lupus erythematosus (SLE) plus secondary anti-phospholipid syndrome (APS) as well as two affected paternal aunts. We compared the frequency of these polymorphisms with healthy controls. Objectives: To evaluate the mode of inheritance in this familial case of APS and SLE and the possible association of plasminogen activator inhibitor-1 (PAI-1) -675 4G/5G and PAI-2 Ser413/Cys polymorphisms. To compare the genotype frequency of these polymorphisms with the results found in a Mexican Mestizo population. Methods: PAI-1 -675 4G/5G and PAI-2 Ser413/Cys were determined by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique using Bsl I and Mwo I on four generations of the family studied. PAI-2 Ser413/Cys polymorphism was also determined in 50 healthy individuals of Mexican Mestizo origin. Results: The family pedigree demonstrated that this family did not follow a Mendelian inheritance pattern. When the PAI-2 Ser413/Cys polymorphism was examined, we found that 60% (3/5) of the relatives homozygous to Ser413/Ser were affected with SLE and/or APS (p = 0.027). The proband case was 4G/5G genotype for the PAI-1 -675 4G/5G polymorphism. No differences between healthy controls of the Mexican Mestizo population and the family studied for the PAI-2 Ser413/Cys polymorphism or PAI-1 -675 4G/5G polymorphisms were found. Conclusions: Our data indicate that this family did not follow the Mendelian inheritance pattern. The Ser413/Ser genotype demonstrated in 60% of the affected members (3/5) of this family might increase the risk for autoimmune syndromes such as APS or SLE. " 2007 Taylor & Francis on license from Scandinavian Rheumatology Research Foundation.",,,,,,"10.1080/03009740601089648",,,"http://hdl.handle.net/20.500.12104/41733","http://www.scopus.com/inward/record.url?eid=2-s2.0-34547493556&partnerID=40&md5=e7eac049d56035f38602789c05ffdbbf",,,,,,"3",,"Scandinavian Journal of Rheumatology",,"20