Inclusion-body myositis and primary Sjögren syndrome: mechanisms for shared etiologies.

Herein we report a case of sporadic inclusion-body myositis (sIBM) occurring at an unusually young age in a patient with primary Sjögren syndrome, and use the case to explore possible shared mechanisms for disease susceptibility. Possible factors may include the association of both conditions with the 8.1 ancestral haplotype; the presence of anti-cN1A antibodies, which, although considered specific for sIBM, are also seen in pSS; and the shared association with T-cell large granular lymphocyte leukemia (T-LGLL). Further evaluation of this patient did in fact reveal underlying T-LGLL and mechanisms by which T cells in sIBM may escape immune regulation and contribute to disease phenotype are explored. Despite myofiber infiltration with CD8-positive T cells in sIBM, and, although sIBM is traditionally considered treatment-refractory, we report a significant response to the anti-CD20 monoclonal antibody, rituximab, and discuss possible mechanisms by which this response may be mediated.

Major histocompatibility complex class I and II expression in idiopathic inflammatory myopathy.

INTRODUCTION: We sought to study the intensity and pattern of major histocompatibility complex (MHC) I and II expression in muscle from patients with biopsy-proven idiopathic inflammatory myositis (IIM) including the subgroups, polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM). METHODS: A total of 120 muscle biopsies (61 PM, 14 DM, and 45 IBM) were immunostained for MHC I and II. Staining was graded as follows. 0: no staining, 1+: ≤10% fibers, 2+: 10% to 25%, 3+: 25% to 50%, 4+: 50% to 99%, and 5+ 100%. RESULTS: All IIM biopsies showed MHC I positivity; 93% showed MHC II positivity. The proportion of patients with MHC II score ≥3+ was higher in IBM than DM or PM. In DM, MHC I expression showed a perifascicular pattern. All IBM biopsies were immunopositive for MHC I and II; 30/45 were scored 5+. DISCUSSION: Immunostaining for MHC I and II is a useful adjunctive test in diagnosis and subclassification of IIM.

A three-way interplay of DR4, autoantibodies and synovitis in biopsy-proven idiopathic inflammatory myositis.

The aim of this study was to determine the HLA and autoantibody associations of patients with histologically confirmed idiopathic inflammatory myositis (IIM). Serum and DNA were archived from South Australian patients with biopsy-proven dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM). HLA typing for Class I and II alleles was performed by serology and DNA-based technology, respectively, for 133 myositis patients and 166 Caucasian population-based controls. Myositis-specific and myositis-associated autoantibodies were detected by line immunoblot. All alleles of the 8.1AH were associated with myositis susceptibility. The B8-DR3 haplotype fragment conferred the strongest susceptibility (OR 2.9, 95% CI 1.8-4.6), and the B-DR region of other ancestral haplotypes was associated with myositis subgroups. Autoantibodies were present in 42/130 (32%) IIM patients and were more frequent in DM (11/17, 65%) than PM (23/70, 33%) or IBM (8/43, 19%), P = 0.002. Autoantibodies were associated with DRB1 03 (P = 0.0005) but also with DRB1 04 (P = 0.004). The frequency of autoantibodies in the three myositis subgroups mirrored the frequency of DR4. Polyarthralgia (±synovitis) was more common in DM/PM (30/76, 39%) than IBM (3/32, 9%), P = 0.004, and there was a strong ordinal association between the prevalence of autoantibodies and polyarthralgia ± synovitis (proportional OR = 5.5, 95% CI 2.3-13.7, P = 0.0004). The central MHC region confers the strongest susceptibility for IIM and also modulates disease phenotype. Our findings reveal a novel association of autoantibodies with DR4 and with arthralgia/synovitis in IIM and raise the possibility of a genetically (DR4) determined citrullination of myositis autoantigens expressed in muscle and synovium.

Pulsed intravenous cyclophosphamide for sle retinal vasculitis.

PURPOSE: To report a case of systemic lupus erythematosus vaso-occlusive retinopathy with severe visual loss treated with intravenous pulsed cyclophosphamide. METHODS: Retrospective interventional case report. RESULTS: A 20-year-old Cambodian woman with newly diagnosed systemic lupus erythematosus presented with acute visual loss. Fluorescein fundus angiography demonstrated occlusive retinal vasculitis. Treatment with pulsed intravenous cyclophosphamide, intravenous methylprednisolone, and anticoagulation resulted in recovery of vision from count fingers to 6/6 in both eyes. CONCLUSION: Early aggressive immunosuppression and anticoagulation for systemic lupus erythematosus retinal vasculitis can be beneficial in preventing disease progression and restoring vision. Further studies are needed to compare dosage regimens.

Idiopathic inflammatory myositis is associated with a high incidence of hypertension and diabetes mellitus.

AIMS: The long-terms complications of immunosuppressive and anti-inflammatory treatment in idiopathic inflammatory myositis (IIM) are unknown. We sought to determine the complications of these treatments in a large cohort of patients with biopsy-proven IIM. METHODS: A South Australian database for patients with biopsy-proven IIM was established. Clinical details of patients including treatment received were recorded. RESULTS: Forty-three patients with dermatomyositis (DM), 184 with polymyositis (PM) and 117 with inclusion body myositis (IBM) were registered on the database. The prevalence of hypertension and diabetes in this population was 62% and 29%, respectively, considerably higher than the background prevalence of 9.4% and 4%, making detection of treatment-related adverse effects difficult. Hypertension and ischemic heart disease were more likely to be present prior to the diagnosis of IIM rather than following it. Hypertension and diabetes occurred more frequently following the diagnosis of myositis, in patients with DM compared with PM or IBM. CONCLUSIONS: We report a novel association of IIM with hypertension, diabetes and ischemic heart disease, indicating that a comprehensive assessment of vascular risk factors is essential in IIM.

Anti-Ro52 antibodies, antisynthetase antibodies, and antisynthetase syndrome.

We present a case of antisynthetase syndrome manifesting with interstitial lung disease, mechanic's hands, nailfold abnormalities, and subclinical myositis, in the presence of antibodies to the aminoacyl tRNA synthetase PL-12 and also to Ro52. Antibodies to Ro52 have been recently associated with idiopathic inflammatory myositis, but there have only been occasional reports of this antibody occurring in association with aminoacyl tRNA synthetases, including PL-12. Our case adds to the descriptions of the concurrence of antibodies to PL-12 and Ro52. The mechanism for the coupling of antibody response remains elusive but is likely to play a fundamental role in disease pathogenesis.