▣ 10.1 Brief History of IBM: A few highlights.

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 Early descriptions of inclusion body myositis are fairly disjointed and some did not reflect the disease we know today as inclusion body myositis.

 1965: First case report made by Adams, who described inclusions in the muscles of a 20-year-old male (Kagen, 2009).

 1967: Chou described inclusions in the muscle cells of a 60-year-old man with "chronic polymyositis."

 1970: A case reported by Carpenter and Karpati of a 39-year-old woman, with a progressive myopathy for 10 years.

 1971: Yunis & Samaha first used the term inclusion body myositis.

 1975: Mitochondrial abnormalities in IBM muscle identified by Carpenter and Karpati.

 These early reports led to the recognition that inclusion body myositis might be a distinct disease (Kagen, 2009).

 1977: Early reference to inclusion body myositis as a viral disease (Ketelsen).

 1978: Carpenter and Karpati describe the abnormal filaments in muscle cells necessary for definite diagnosis. First mention that IBM does not improve with corticosteroid treatment.

 1984: Arahata, & A. G. Engel described the inflammation in IBM and identified cytotoxic CD8 + T cells invading muscle cells.

 1981: Nonaka and his team described a form of muscular disorder essentially the same as autosomal recessive inclusion body myopathy type 2 (IBM2).

 1984: Argov and Yarom describe hereditary Inclusion Body Myopathy (Autosomal Recessive; IBM2) in Jews of Persian origin, characterized by lack of inflammation and quadriceps sparing. They use the term myopathy to distinguish it from the spontaneous myositis form characterized by inflammation.

 1988: Karpati describes how MHC class I molecules are expressed on myofibers in s-IBM.

 1988: Arahata and Engel identify evidence of cell-mediated cytotoxicity showing that autoinvasive CD8+ T cells surround MHC class I-immunoreactive myofibers and express perforin and other markers of activation.

 1989: Lotz reviewed 40 cases and concluded that IBM should be considered a distinct disease. Data were consistent with previous observations that corticosteroid therapy (usually prednisone) does not work in IBM.

 1990: Baumbach reports the first familial cases of inclusion body myositis.

 1991: Mendell describes using Congo red stain to detect the presence of amyloid in the inclusions found in IBM muscle cells.

 1992: Askanas & W. K. Engel outline the beta-amyloid theory.

 1993: Askanas and Engel note the similarities between the pathology of sIBM muscle and brains affected by Alzheimer's disease: the accumulation of ubiquitin, beta-amyloid protein and its precursor protein, alpha 1-antichymotrypsin, and hyperphosphorylated tau.

 1993: Askanas and Engel introduce the term hereditary IBM.

 1993: Oldfors describes mitochondrial abnormalities in IBM.

 1994: Garlepp reports sIBM is associated with a group of genes linked to the immune system called HLA-DR3 and with the extended 8.1AH. This group of genes is associated with some of the most common autoimmune diseases and is relatively abundant people in the western hemisphere.

 1995: Griggs describes diagnostic criteria for IBM.

 1996: Mirabella demonstrates antibodies (SMI-31) react with paired-helical filaments (PHFs) that characterize sIBM and the hereditary inclusion-body myopathies. SMI-31 can be used for identifying and distinguishing s-IBM and the h-IBMs.

 1998: The first book on IBM is published, Askanas, Serratrice, and Engel, editors.

 1998: Darin describes autosomal dominant inclusion body myopathy 3, (IBM3).

 1999: Eisenberg localizes the gene for Inclusion Body Myopathy 2 (Autosomal Recessive; IBM2) in Middle Eastern Jews.

 2002: Sugarman. The first animal model of inclusion body myositis is developed. The report also notes that the accumulation of amyloid-beta peptide, which is derived from the larger amyloid-beta precursor protein (betaAPP), seems to be an early pathological event in Alzheimer's disease and in sIBM.

 2002: Tawil improves diagnostic criteria.

 2004: Price shows another group of genes linked to the immune system, the 35.2AH

 2004: Price shows another group of genes linked to the immune system, the 35.2AH

 2004: Price shows another group of genes linked to the immune system, the 35.2AH appear to be associated with sIBM in Caucasians.

 2004: Fratta reports that the majority of muscle fibers in sporadic inclusion body myositis contain strong immunoreactivity to mutant ubiquitin (UBB+1). Fratta suggests that the UBB+1-inhibited proteasome cannot properly degrade toxic proteins, resulting in their accumulation and aggregation.

 2005: A major conference on s-IBM. 22 articles were published in Neurology (Volume 66(2) Supplement 1 January 24, 2006).

 2006: Askanas & W. K. Engel, describe beta amyloid protein in IBM.

 2006: Dalakas found in addition to the vacuoles and inclusions, muscle tissue in inclusion body myositis shows an inflammatory invasion of intact muscle cells by macrophages and cytotoxic CD8 + T cells.

 2007: Askanas & W. K. Engel point out that muscle cell degeneration is characterized by progressive cell death, of the development of vacuoles, and the accumulation of clumps made up of different proteins—amyloid inclusion bodies. The amyloid inclusions are of two types, one of which contains beta amyloid protein, and the other, tau protein.

 2008: Chahin stated that rimmed vacuoles are absent in 20% of patients with typical clinical features of IBM.

 2008: TDP-43 is identified by Weihl and colleagues in non-nuclear sarcoplasm in sIBM and hereditary inclusion body myopathy (hIBM) due to VCP mutations.

 2009: The "beta amyloid hypothesis of IBM" is taken to task by Greenberg. Greenberg (2009 Curr Neurol Neurosci Rep.) addressed limitations in the beta-amyloid-mediated theory of IBM myofiber injury, flawed rationales of animal models of this disease, and recent reports regarding treatment. Greenberg (2009 Br Med J) demonstrated that distortions in the citation of articles concerning beta-amyloid as created a false impression of the possible role of beta-amyloid in IBM.

 2009: Gene therapy using follistatin to inhibit myostatin holds promise for the treatment of muscle disease. (Rodino-Klapac, 2009).

 2009: The first report of specific muscle protein being reduced in IBM muscle: substantial depletion in fast-twitch sarcomeric and glycolytic enzyme proteins in sIBM samples. (Parker, 2009).

 2009: Following up on earlier leads, the Greenberg group report finding that the protein TDP-43 is a prominent and highly sensitive and specific feature of IBM. This protein is normally found within the nucleus but in IBM is found in the cytoplasm of the cell. (Salajegheh , 2009).

 2010: Pandya identified CD28 + (CD244 - ) a highly differentiated cytotoxic CD8 + T cell in IBM.

 2011: Salajegheh (of the Greenberg group) discovered that a circulating autoantibody against a 43-kDa muscle autoantigen is present in IBM.

 2013: Rose presents The European Neuromuscular Centre (ENMC) diagnostic criteria for IBM.

 2013: The target autoantigen of the IBM [auto]antibody discovered in 2011 was identified simultaneously by two research groups and the findings published in tandem: Larman (of the Greenberg group), Pluk (of the Badrising group) Cytosolic 5' -nucleotidase 1A (cN1A; NT5C1A).

 2016: Greenberg recognizes highly differentiated effector and effector memory CD8 + T cells in IBM muscle and blood overlapping with T cell large granular lymphocytic leukaemia.

 2017: Lilleker described differences in clinical and histopathological features between anticytosolic 5'-nucleotidase 1A antibody positive and negative IBM patients.

 2017: Rothwell reported alleles in the HLA-DRB1 (an autoimmune haplotype) were found to be independently associated with IBM.

 2018: Britson found variants within the HLA locus are genetic risk factors for developing IBM.

 2018: Britton noted 65% to 80% of IBM patients have dysphagia and associated issues with excessive thick mucus.

 2018: Felice reported the anti-cN1A antibody test has a low predictive value for IBM parameters. In our cohort, 20 of 40 (50%) of patients tested positive for anti-cN1A, and, of these, antibodies were strong positive in 12 (60%), moderate positive in 5 (25%), and weak positive in 3 (15%). … Based on all clinical studies published to date including the present, the anti-cN1A antibody test shows low predictive value in regards to disease severity and associated clinicopathological findings.

 2019: Greenberg (2019) pointed out that, despite the finding that less than one percent of muscle cells contain abnormal proteins, for some reason, the degenerative aspects of IBM have dominated past research. Although immune system involvement was seen early on, it has not received as much research attention. Today, mounting evidence that IBM is an autoimmune T cell-mediated disease provides hope for the development of new, immune based therapies.

 2019: Greenberg et al., (2019) described the specific cytotoxic CD8 + T cells responsible for muscle cell destruction in IBM and a marker of these cells (KLRG1).

 2019: Ramdharry presents the latest version of the clinician rated inclusion body myositis functional rating scale.

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