Highly differentiated cytotoxic T cells in inclusion body myositis.

Inclusion body myositis is a late onset treatment-refractory autoimmune disease of skeletal muscle associated with a blood autoantibody (anti-cN1A), an HLA autoimmune haplotype, and muscle pathology characterized by cytotoxic CD8+ T cell destruction of myofibres. Here, we report on translational studies of inclusion body myositis patient muscle compared with a diverse set of other muscle disease samples. Using available microarray data on 411 muscle samples from patients with inclusion body myositis (n = 40), other muscle diseases (n = 265), and without neuromuscular disease (normal, n = 106), we identified a signature of T-cell cytotoxicity in inclusion body myositis muscle coupled with a signature of highly differentiated CD8 T-cell effector memory and terminally differentiated effector cells.

Association of inclusion body myositis with T cell large granular lymphocytic leukaemia.

SEE HOHLFELD AND SCHULZE-KOOPS DOI101093/BRAIN/AWW053 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Inclusion body myositis and T cell large granular lymphocytic leukaemia are rare diseases involving pathogenic cytotoxic CD8+ T cells. After encountering four patients with both disorders, we prospectively screened 38 patients with inclusion body myositis for the presence of expanded large granular lymphocyte populations by standard clinical laboratory methods (flow cytometry, examination of blood smears, and T cell receptor gene rearrangements), and performed muscle immunohistochemistry for CD8, CD57, and TIA1. Most (22/38; 58%) patients with inclusion body myositis had aberrant populations of large granular lymphocytes in their blood meeting standard diagnostic criteria for T cell large granular lymphocytic leukaemia.

α-Hemoglobin-stabilizing Protein: An Effective Marker for Erythroid Precursors in Bone Marrow Biopsy Specimens.

Accurate analysis of the erythroid lineage is essential in evaluating bone marrow biopsies and can be particularly challenging in settings of dyserythropoiesis. α-Hemoglobin-stabilizing protein (AHSP) is an erythroid-specific chaperone protein and represents a potential specific marker for erythroid elements. This study defines the immunohistochemical profile of AHSP, as compared with an established erythroid marker CD71, in 101 bone marrow biopsies including normal marrows and cases of acute pure erythroid leukemia, acute erythroid/myeloid leukemia, other types of acute myeloid leukemia, myelodysplastic syndrome, chronic myelogenous leukemia, other types of myeloproliferative neoplasm, chronic myelomonocytic leukemia, acute lymphoblastic leukemia, plasma cell neoplasm, and metastatic carcinoma.

Profile of CD103 expression in T-cell neoplasms: immunoreactivity is not restricted to enteropathy-associated T-cell lymphoma.

Intestinal intraepithelial T lymphocytes express the α E subunit of integrin αEβ7, which is detected by antibodies to CD103. Accordingly, within T-cell neoplasms, CD103 reactivity has most frequently been reported in enteropathy-associated T-cell lymphomas, which are postulated to arise from intestinal intraepithelial T lymphocytes. However, prior studies of CD103 expression in T-cell neoplasms have been limited by the requirement for fresh or frozen tissue, given the historic lack of an antibody to CD103 for use in paraffin-embedded sections.

Abnormal distribution of heterogeneous nuclear ribonucleoproteins in sporadic inclusion body myositis.

Previous histopathologic studies of sporadic inclusion body myositis (sIBM) identified sarcoplasmic aggregation and myonuclear depletion of the predominantly nuclear heterogeneous nuclear ribonucleoprotein (hnRNP) TDP-43 in sIBM myofibers. Here, we examined sIBM muscle for abnormalities in two other hnRNPs hnRNPA1 and hnRNPA2B1, mutations in which cause multisystem proteinopathy associated with rimmed-vacuolar myopathies. Muscle biopsy specimens from 13 patients with sIBM and 13 patients without sIBM (dermatomyositis N=3, polymyositis N=3, muscular dystrophy N=3, motor neuron disease N=2, non-neuromuscular disease N=2) underwent immunohistochemistry for hnRNPA1, hnRNPA2B1, and TDP-43.