Background A statin-associated autoimmune myopathy with anti-HMGCR antibodies has recently been described. Identification of these patients is of paramount importance because immunosuppressive therapy is usually needed for clinical improvement. Herein we report a new pattern of immunofluorescence (IIF) that could alert of the presence of this antibody in routine autoantibody screening on kidney, liver, stomach sections.
Objectives Our objective was to study the concordance of this IIF pattern with anti-HMGCR in a series of patients with immune-mediated necrotizing myopathy (IMNM).
Methods Seventeen patients diagnosed with IMNM positive for anti-HMGCR antibodies were tested for the presence of IIF pattern. As a control group, 90 patients diagnosed with systemic autoimmune diseases (SLE, autoimmune hepatitis, systemic sclerosis, rheumatoid arthritis, Sjögren syndrome, and dermatomyositis – 15 from each group), and 45 patients treated with statins (15 with familial severe dyslipidemia, 15 with a recent cerebrovascular event – treated high dose of atorvastatin, and 15 from the community) were also studied. Anti-HMGCR antibodies were measured by means of two ELISA assays: a in-house confirmed by blot using hidroxi-methil-glutharil-CoA (Sigma H7039) as antigen and commercial QUANTA Lite HMGCR ELISA Innova (San Diego). Indirect immunofluorescence studies on triple tissue (rat liver, kidney and stomach) was performed using Nova Lite assay (Innova Diagnostic, San Diego, USA). We used different commercial substrates (Innova, Euroimmune, ByoSistems, and Aeskulides) in order to confirm that the reactivity of the pattern do not depend on the commercial source. Indirect immunofluorescence on HEp-2 Slides (INOVA Diagnostics, Inc., San Diego Hep-2 ANA slides) was also performed. Immunoabsorption studies were performed using HMGCR human antigen (Sigma, St Louis, MO,USA) at different dilutions (PBS 10%) in those patients with a positive IIF pattern
Results A cytoplasmatic pattern in scattered hepatocytes with perivascular distribution was observed in 15 out of 17 (88%) IMNM positive for anti-HMGCR antibodies. No patients from the autoimmune systemic disease group or those treated with statins disclosed this characteristic pattern. Consequently, the overall agreement between rat triple tissue IIF and ELISA confirmed by blot was 98.7% (kappa 0.93). Dispersed hepatocyte cytoplasmatic pattern (DHCP) was specifically absorbed by incubation with human purified antigen. A granular cytoplasmatic fluorescence pattern was observed in 6 out of 17 (35%) patients with human Hep cells.
Conclusions A new distinctive IIF pattern on routine rat triple tissue is described in patients diagnosed with IMNM whit anti-HMGCR antibodies. It could be useful to alert of the presence of anti-HMGCR antibodies when performing a routine unexpensive autoantibody profile.
Disclosure of Interest None declared