Tumefactive demyelinating lesions: a retrospective cohort study in Thailand.

Tumefactive demyelinating lesions (TDL), characterized by large (≥ 2 cm) demyelinating lesions mimicking tumors, are a rare manifestation of the central nervous system inflammatory demyelinating diseases (CNS-IDD). Distinguishing TDL from other brain lesions can be challenging, often necessitating biopsy or advanced diagnostics. The natural history of TDL varies among races. This study aimed to assess demographics, clinical and radiological features, laboratory findings, management, and outcomes of Thai patients with TDL. We retrospectively reviewed records of twenty-six patients with TDL from the Multiple Sclerosis and Related Disorders registry from two tertiary medical centers. Among 1102 CNS-IDD patients, 26 (2.4%) had TDL. The median age at TDLs onset was 34.5 years (range 17-75); 69.2% were female. Over 70% manifested TDL as their initial CNS-IDD presentation. Common presenting symptoms included motor deficits, sensory disturbances, and cognitive problems. About two-fifths exhibited multiple lesions, most frequently in the frontoparietal region (46.2%). Half of the patients showed an incomplete ring on post-contrast T1-weighted imaging, with peripheral diffusion-weighted imaging restriction in twenty-one patients. T2-hypointense rims were present in thirteen (56.5%) patients. Brain biopsy was performed in 12 cases (46.1%). Serum aquaporin-4 immunoglobulin was positive in 16.7% of tested (4/24) cases. Serum myelin oligodendrocyte glycoprotein immunoglobulin was negative in all thirteen patients tested. Twenty patients (76.9%) received intravenous corticosteroids for TDL attacks. After the median follow-up period of 48 months (range 6-300), 23.1% experienced CNS-IDD relapses. Median Expanded Disability Status Scale at TDL diagnosis was 4.3 (range 0.0-9.5), and improved to 3.0 (range 0.0-10.0) at the last follow-up. This study suggested that TDL were rare among Thai CNS-IDD patients, frequently presenting as a monophasic condition with a favorable outcome.

Exploiting nanopore sequencing for characterization and grading of IDH-mutant gliomas.

The 2021 WHO Classification of Central Nervous System Tumors recommended evaluation of cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion in addition to codeletion of 1p/19q to characterize IDH-mutant gliomas. Here, we demonstrated the use of a nanopore-based copy-number variation sequencing (nCNV-seq) approach to simultaneously identify deletions of CDKN2A/B and 1p/19q. The nCNV-seq approach was initially evaluated on three distinct glioma cell lines and then applied to 19 IDH-mutant gliomas (8 astrocytomas and 11 oligodendrogliomas) from patients. The whole-arm 1p/19q codeletion was detected in all oligodendrogliomas with high concordance among nCNV-seq, FISH, DNA methylation profiling, and whole-genome sequencing. For the CDKN2A/B deletion, nCNV-seq detected the loss in both astrocytoma and oligodendroglioma, with strong correlation with the CNV profiles derived from whole-genome sequencing (Pearson correlation (r) = 0.95, P < 2.2 × 10-16 to r = 0.99, P < 2.2 × 10-16 ) and methylome profiling. Furthermore, nCNV-seq can differentiate between homozygous and hemizygous deletions of CDKN2A/B. Taken together, nCNV-seq holds promise as a new, alternative approach for a rapid and simultaneous detection of the molecular signatures of IDH-mutant gliomas without capital expenditure for a sequencer.

Association Between HLA Alleles and Autoantibodies in Dermatomyositis Defined by Sarcoplasmic Expression of Myxovirus Resistance Protein A.

OBJECTIVE: The diagnosis in the studies analyzing HLA of dermatomyositis (DM) was based on a combined clinical category of polymyositis/DM. This retrospective study investigated the associations of HLA with 5 DM-specific autoantibodies in Japanese patients diagnosed by muscle pathology. METHODS: We diagnosed Japanese patients with DM based on sarcoplasmic expression of myxovirus resistance protein A. These patients underwent investigation for 5 DM-specific autoantibodies and HLA genotyping. RESULTS: Of 175 patients (83 males and 92 females; range 1-86 yrs; mean 46 yrs), 173 (98.9%) had 1 of the 5 autoantibodies. Seven alleles-A*02:07, B*46:01, DRB1*04:07, DRB1*07:01, DRB1*08:03, DQB1*06:01, and DPB1*02:02-were more frequently detected in the patients with DM than healthy controls, but these associations were not significant after multiple testing correction. Stratifying by DM-specific autoantibodies, we found the associations of 6 already known and 7 new alleles-B*48:01, B*52:01, C*12:02, DRB1*04:05, DRB1*15:02, DPB1*05:01, and DPB1*09:01-with subsets of DM. Moreover, significant associations of 5 alleles with antinucleosome remodeling deacetylase complex (Mi-2) remained after multiple testing correction. In particular, the DRB1*04:07 (odds ratio [OR 28.9]; corrected P = 2.7 × 10-6) and DQB1*06:01 (OR 4.0; corrected P = 1.6 × 10-4) alleles were significantly more prevalent in patients with anti-Mi-2 antibody than in controls. CONCLUSION: This study demonstrates DM-specific autoantibodies defined immunogenetic subsets of DM.

Muscle pathology of antisynthetase syndrome according to antibody subtypes.

Identification of antisynthetase syndrome (ASS) could be challenging due to inaccessibility and technical difficulty of the serology test for the less common non-Jo-1 antibodies. This study aimed to describe ASS antibody-specific myopathology and evaluate the diagnostic utility of myofiber HLA-DR expression. We reviewed 212 ASS muscle biopsies and compared myopathologic features among subtypes. Additionally, we compared their HLA-DR staining pattern with 602 non-ASS myositis and 140 genetically confirmed myopathies known to have an inflammatory component. We used t-test and Fisher's exact for comparisons and used sensitivity, specificity, positive and negative predictive values to assess the utility of HLA-DR expression for ASS diagnosis. RNAseq performed from a subset of myositis cases and histologically normal muscle biopsies was used to evaluate interferon (IFN)-signaling pathway-related genes. Anti-OJ ASS showed prominent myopathology with higher scores in muscle fiber (4.6 ± 2.0 vs. 2.8 ± 1.8, p = 0.001) and inflammatory domains (6.8 ± 3.2 vs. 4.5 ± 2.9, p  = 0.006) than non-OJ ASS. HLA-DR expression and IFN-γ-related genes upregulation were prominent in ASS and inclusion body myositis (IBM). When dermatomyositis and IBM were excluded, HLA-DR expression was 95.4% specific and 61.2% sensitive for ASS with a positive predictive value of 85.9% and a negative predictive value of 84.2%; perifascicular HLA-DR pattern is common in anti-Jo-1 ASS than non-Jo-1 ASS (63.1% vs. 5.1%, p < 0.0001). In the appropriate clinicopathological context, myofiber HLA-DR expression help support ASS diagnosis. The presence of HLA-DR expression suggests involvement of IFN-γ in the pathogenesis of ASS, though the detailed mechanisms have yet to be elucidated.

Update on dermatomyositis.

PURPOSE OF REVIEW: This review summarizes and comments on current knowledge in dermatomyositis. RECENT FINDINGS: The 2018 European Neuromuscular Centre classification of dermatomyositis has been challenging by the discovery of clinicopathological features associated with dermatomyositis-specific antibody (DMSA) that were not incorporated in the original criteria. These features include but may not be limited to the presence of perifascicular necrosis in anti-Mi-2 dermatomyositis; presence of diffuse nonperifascicular sarcoplasmic myxovirus resistance protein A expression in anti-MDA5 dermatomyositis; and dermatomyositis sine dermatitis in anti-NXP-2 dermatomyositis. Variations and subclassifications within the same DMSA subtypes are observed: anti-MDA5 dermatomyositis is clinically subcategorized into good, intermediate, and poor prognostic subgroups; concurrent anti-CCAR1 and anti-TIF1-γ positivity identify anti-TIF1-γ-positive patient with a lower risk for cancer-associated myositis. Owing to distinct IFN1-signaling pathway activation in dermatomyositis, JAK-STAT inhibitor - the pathway-targeted therapy, have been studied with promising results in refractory dermatomyositis and some new-onset dermatomyositis. In addition, the potential serum biomarkers for IFN1 pathway activation are being investigated for their performance in monitoring the disease activity and the efficacy of the treatment. SUMMARY: DMSA, evidence of prominent IFN1 pathway activation, and risk/severity-associated biomarkers would likely play major roles in future dermatomyositis classification, disease monitoring, and treatment decision.

Reliability of antinuclear matrix protein 2 antibody assays in idiopathic inflammatory myopathies is dependent on target protein properties.

A line blotting assay (LB) is currently used to detect myositis-specific autoantibodies (MSAs) in patients with idiopathic inflammatory myopathies (IIMs), because of its simplicity; however, the sensitivity and specificity of this assay is low. The aim of this study is to evaluate the accuracy of the commercial LB in detection of antinuclear matrix protein 2 (NXP2) antibody. Seventy-seven serum samples from patients with IIMs, in which anti-NXP2 antibodies were detected through immunoprecipitation and western blotting (IP-WB) using K562 cell lysate, were enrolled. All samples were assessed by LB and IP-WB using recombinant human NXP2 whole protein (rNXP2) produced by insect cells, and the positive rates of each assay were compared. Thirty-two samples (41.6%) showed false-negativity by LB, which includes 11 samples with negative results by IP-WB using rNXP2. Relative intensities of IP-WB using cell lysate were significantly higher in the samples with positive results by both LB and IP-WB using rNXP2, compared to samples with positive by IP-WB using rNXP2 but negative by LB. Three of 11 samples with negative results by both LB and IP-WB using rNXP2 revealed high antibody titers. Further, differences in post-transcriptional SUMOylation were observed between recombinant and natural NXP2 proteins. In conclusion, the LB showed low sensitivity for detection of anti-NXP2 antibody, an effect exacerbated at low titers of anti-NXP2 antibodies. Moreover, there appears to be differences in the reactivities of antibodies to recombinant and natural NXP2 proteins with different post-transcriptional modifications.

Dermatomyositis: Muscle Pathology According to Antibody Subtypes.

BACKGROUND AND OBJECTIVES: Discoveries of dermatomyositis-specific antibodies (DMSAs) in patients with dermatomyositis raised awareness of various myopathologic features among antibody subtypes. However, only perifascicular atrophy and perifascicular myxovirus resistant protein A (MxA) overexpression were officially included as definitive pathologic criteria for dermatomyositis classification. We aimed to demonstrate myopathologic features in MxA-positive dermatomyositis to determine characteristic myopathologic features in different DMSA subtypes. METHODS: We performed a retrospective pathology review of muscle biopsies of patients with dermatomyositis diagnosed between January 2009 and December 2020 in a tertiary laboratory for muscle diseases. We included all muscle biopsies with sarcoplasmic expression for MxA and seropositivity for DMSAs. MxA-positive muscle biopsies that tested negative for all DMSAs were included as seronegative dermatomyositis. We evaluated histologic features stratified according to 4 pathology domains (muscle fiber, inflammatory, vascular, and connective tissue) and histologic features of interest by histochemistry, enzyme histochemistry, and immunohistochemical study commonly used in the diagnosis of inflammatory myopathy. We performed ultrastructural studies of 54 available specimens. RESULTS: A total of 256 patients were included. Of these, 249 patients were positive for 1 of the 5 DMSAs (seropositive patients: 87 anti-transcription intermediary factor 1-γ [TIF1-γ], 40 anti-complex nucleosome remodeling histone deacetylase [Mi-2], 29 anti-melanoma differentiation gene 5 [MDA5], 83 anti-nuclear matrix protein 2 [NXP-2], and 10 anti-small ubiquitin-like modifier-activating enzyme [SAE] dermatomyositis) and 7 patients were negative for all 5 DMSAs (seronegative patients). Characteristic myopathologic features in each DMSA subtype were as follows: anti-TIF1-γ with vacuolated/punched out fibers (64.7%; p < 0.001) and perifascicular enhancement in HLA-ABC stain (75.9%; p < 0.001); anti-Mi-2 with prominent muscle fiber damage (score 4.9 ± 2.1; p < 0.001), inflammatory cell infiltration (score 8.0 ± 3.0; p = 0.002), perifascicular atrophy (67.5%; p = 0.02), perifascicular necrosis (52.5%; p < 0.001), increased perimysial alkaline phosphatase activity (70.0%; p < 0.001), central necrotic peripheral regenerating fibers (45.0%; p = 0.002), and sarcolemmal membrane attack complex deposition (67.5%; p < 0.001); anti-MDA5 with scattered/diffuse staining pattern of MxA (65.5%; p < 0.001) with less muscle pathology and inflammatory features; anti-NXP-2 with microinfarction (26.5%; p < 0.001); and anti-SAE and seronegative dermatomyositis with HLA-DR expression (50.0%; p = 0.02 and 57.1%; p = 0.02, respectively). DISCUSSION: We describe a comprehensive serologic-pathologic correlation of dermatomyositis primarily using MxA expression as an inclusion criterion. In our study, DMSAs were associated with distinctive myopathologic features suggesting different underlying pathobiologic mechanisms in each subtype.

Deep convolutional neural network-based algorithm for muscle biopsy diagnosis.

Histopathologic evaluation of muscle biopsy samples is essential for classifying and diagnosing muscle diseases. However, the numbers of experienced specialists and pathologists are limited. Although new technologies such as artificial intelligence are expected to improve medical reach, their use with rare diseases, such as muscle diseases, is challenging because of the limited availability of training datasets. To address this gap, we developed an algorithm based on deep convolutional neural networks (CNNs) and collected 4041 microscopic images of 1400 hematoxylin-and-eosin-stained pathology slides stored in the National Center of Neurology and Psychiatry for training CNNs. Our trained algorithm differentiated idiopathic inflammatory myopathies (mostly treatable) from hereditary muscle diseases (mostly non-treatable) with an area under the curve (AUC) of 0.996 and achieved better sensitivity and specificity than the diagnoses done by nine physicians under limited diseases and conditions. Furthermore, it successfully and accurately classified four subtypes of the idiopathic inflammatory myopathies with an average AUC of 0.958 and classified seven subtypes of hereditary muscle disease with an average AUC of 0.936. We also established a method to validate the similarity between the predictions made by the algorithm and the seven physicians using visualization technology and clarified the validity of the predictions. These results support the reliability of the algorithm and suggest that our algorithm has the potential to be used straightforwardly in a clinical setting.

Anti-nuclear matrix protein 2 antibody-positive inflammatory myopathies represent extensive myositis without dermatomyositis-specific rash.

OBJECTIVES: Myositis-specific autoantibodies (MSAs) define distinct clinical subsets of idiopathic inflammatory myopathies (IIMs). The anti-nuclear matrix protein 2 (NXP2) antibody, a MSA detected in juvenile/adult IIMs, has been reported to be associated with a high risk of subcutaneous calcinosis, subcutaneous oedema and internal malignancies. The study aimed to clarify the clinical features of anti-NXP2 antibody-positive IIMs in detail. METHODS: This was a multicentre retrospective observational study on 76 anti-NXP2 antibody-positive patients. The antibody was detected via a serological assay using immunoprecipitation and western blotting. The patients were selected from 162 consecutive Japanese patients with IIMs. RESULTS: The cohort of anti-NXP2 antibody-positive IIMs included 29 juvenile patients and 47 adult patients. Twenty-seven (35.5%) patients presented with polymyositis phenotype without dermatomyositis-specific skin manifestations (heliotrope rash or Gottron sign/papules); this was more common in the adults than children (48.9% vs 15.8%, P < 0.01). Nine (11.8%) patients had subcutaneous calcinosis, and 20 (26.3%) patients had subcutaneous oedema. In addition, the proportion of patients with muscle weakness extending to the distal limbs was high (36 patients [47.4%]) in this cohort. Adult patients had a higher prevalence of malignancy than the general population (age-standardized incidence ratio of malignancies: 22.4). CONCLUSION: Anti-NXP2 antibody-positive IIMs, which include dermatomyositis sine dermatitis, are characterized by atypical skin manifestations and extensive muscular involvement.

Inflammatory features in sporadic late-onset nemaline myopathy are independent from monoclonal gammopathy.

Sporadic late-onset nemaline myopathy (SLONM) is a rare adult-onset non-hereditary disease with subacute proximal muscle and often axial muscle weakness, characterized by the presence of nemaline bodies in skeletal muscle biopsies. Considering its association with concurrent monoclonal gammopathy of undetermined significance (MGUS), the disease is classified into two major subtypes (1) SLONM without MGUS (SLONM-noMGUS) and (2) with MGUS (SLONM-MGUS) association. SLONM associated with HIV infection (SLONM-HIV) is also reported. SLONM-MGUS has been shown to be associated with poorer prognosis and required aggressive treatment including high-dose melphalan and autologous stem cell transplantation. The approach is currently debatable as recent reports suggested effectiveness of intravenous immunoglobulin as initial treatment with indifference of overall survival despite the presence of MGUS. Our study aimed to find an underlying basis by review of pathological features in 49 muscle biopsy proven-SLONM from two large tertiary centers in Japan and Germany (n = 49: SLONM-noMGUS = 34, SLONM-MGUS = 13, SLONM-HIV = 2). We compared pathological findings in SLONM-noMGUS and SLONM-MGUS and focused on the presence of any detectable inflammatory features by immunohistochemistry. The clinical and histological features in SLONM-noMGUS and SLONM-MGUS were not distinctively different except for more common regenerating fibers (>5% of myofibers) present in SLONM-MGUS (p < 0.01). HLA-ABC expression and fine granular p62 were observed in 66.7% and 78.3% of SLONM, respectively. The predominant inflammatory cells were CD68+ cells. The inflammatory cells showed positive correlations with the percentage of nemaline-containing fibers (p < 0.001). In conclusion, inflammatory features are present although rather mild in SLONM. This finding contributes to the hypothesis of an acquired inflammatory disease pathogenesis and opens the possibility to offer immunotherapy in SLONM with inflammatory features regardless of the monoclonal gammopathy status.

Simplified approach for pathological diagnosis of diffuse gliomas in adult patients.

The most recent WHO classification (2016) for gliomas introduced integrated diagnoses requiring both phenotypic and genotypic data. This approach presents difficulties for countries with limited resources for laboratory testing. The present study describes a series of 118 adult Thai patients with diffuse gliomas, classified by the WHO 2016 classification. The purpose was to demonstrate how a diagnosis can still be achieved using a simplified approach that combines clinical, morphological, immunohistochemical, and fewer molecular assays than typically performed. This algorithm starts with tumor location (midline vs. non-midline) with diffuse midline glioma identified by H3 K27M immunostaining. All other tumors are placed into one of 6 categories, based on morphologic features rather than specific diagnoses. Molecular testing is limited to IDH1/IDH2 mutations, plus co-deletion of 1p/19q for cases with oligodendroglial features and TERT promoter mutation for cases without such features. Additional testing for co-deletion of 1p/19q, TERT promoter mutation and BRAF mutations are only used in selected cases to refine diagnosis and prognosis. With this approach, we were able to reach the integrated diagnosis in 117/118 cases, saving 50 % of the costs of a more inclusive testing panel. The demographic data and tumor subtypes were found to be similar to series from other regions of the world. To the best of our knowledge, this is to the first reported series of diffuse gliomas in South-East Asia categorized by the WHO 2016 classification system.

Biallelic variants in LIG3 cause a novel mitochondrial neurogastrointestinal encephalomyopathy.

Abnormal gut motility is a feature of several mitochondrial encephalomyopathies, and mutations in genes such as TYMP and POLG, have been linked to these rare diseases. The human genome encodes three DNA ligases, of which only one, ligase III (LIG3), has a mitochondrial splice variant and is crucial for mitochondrial health. We investigated the effect of reduced LIG3 activity and resulting mitochondrial dysfunction in seven patients from three independent families, who showed the common occurrence of gut dysmotility and neurological manifestations reminiscent of mitochondrial neurogastrointestinal encephalomyopathy. DNA from these patients was subjected to whole exome sequencing. In all patients, compound heterozygous variants in a new disease gene, LIG3, were identified. All variants were predicted to have a damaging effect on the protein. The LIG3 gene encodes the only mitochondrial DNA (mtDNA) ligase and therefore plays a pivotal role in mtDNA repair and replication. In vitro assays in patient-derived cells showed a decrease in LIG3 protein levels and ligase activity. We demonstrated that the LIG3 gene defects affect mtDNA maintenance, leading to mtDNA depletion without the accumulation of multiple deletions as observed in other mitochondrial disorders. This mitochondrial dysfunction is likely to cause the phenotypes observed in these patients. The most prominent and consistent clinical signs were severe gut dysmotility and neurological abnormalities, including leukoencephalopathy, epilepsy, migraine, stroke-like episodes, and neurogenic bladder. A decrease in the number of myenteric neurons, and increased fibrosis and elastin levels were the most prominent changes in the gut. Cytochrome c oxidase (COX) deficient fibres in skeletal muscle were also observed. Disruption of lig3 in zebrafish reproduced the brain alterations and impaired gut transit in vivo. In conclusion, we identified variants in the LIG3 gene that result in a mitochondrial disease characterized by predominant gut dysmotility, encephalopathy, and neuromuscular abnormalities.

Pathologic Features of Anti-Mi-2 Dermatomyositis.

OBJECTIVE: To identify the characteristic pathologic features of dermatomyositis (DM) associated with anti-Mi-2 autoantibodies (anti-Mi-2 DM). METHODS: We reviewed 188 muscle biopsies from patients (1) pathologically diagnosed with DM through the sarcoplasmic expression for the myxovirus-resistant protein A and (2) serologically positive for 1 of 5 DM-specific autoantibodies (DMSAs) (anti-Mi-2, n = 30; other DMSAs, n = 152) or negative for all 5 DMSAs (n = 6). We then compared the histopathologic and immunohistochemical features of patients with anti-Mi-2 DM to those with non-Mi-2 DM and patients with anti-synthetase syndrome (ASS) (n = 212) using the t test, Fisher exact test, and a logistic regression model. RESULTS: Patients with anti-Mi-2 DM showed significantly higher severity scores in muscle fiber and inflammatory domains than non-Mi-2 DM patients. The presence of perifascicular necrosis, increased perimysial alkaline phosphatase activity, and sarcolemmal membrane attack complex deposition was more frequent in patients with anti-Mi-2 DM (p < 0.01). After Bonferroni correction, there were no significant differences in the percentages of the features mentioned above between the patients with anti-Mi-2 DM and those with ASS (p > 0.01). CONCLUSION: Perifascicular necrosis and perimysial pathology, features previously reported in ASS, are common in patients with anti-Mi-2 DM. Our findings not only assist in differentiating anti-Mi-2 DM from other DM subtypes but also suggest the possibility of an overlapping mechanism between anti-Mi-2 DM and ASS. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the muscle biopsies of DM patients with anti-Mi-2 autoantibodies are more likely to demonstrate higher severity scores in muscle fiber and inflammatory domains.

Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores.

The myosin-directed chaperone UNC-45B is essential for sarcomeric organization and muscle function from Caenorhabditis elegans to humans. The pathological impact of UNC-45B in muscle disease remained elusive. We report ten individuals with bi-allelic variants in UNC45B who exhibit childhood-onset progressive muscle weakness. We identified a common UNC45B variant that acts as a complex hypomorph splice variant. Purified UNC-45B mutants showed changes in folding and solubility. In situ localization studies further demonstrated reduced expression of mutant UNC-45B in muscle combined with abnormal localization away from the A-band towards the Z-disk of the sarcomere. The physiological relevance of these observations was investigated in C. elegans by transgenic expression of conserved UNC-45 missense variants, which showed impaired myosin binding for one and defective muscle function for three. Together, our results demonstrate that UNC-45B impairment manifests as a chaperonopathy with progressive muscle pathology, which discovers the previously unknown conserved role of UNC-45B in myofibrillar organization.

A Cavernous Venous Malformation of the Orbit Mimicking an Idiopathic Orbital Inflammation.

Orbital cavernous venous malformations (CVMs) are usually slow progressing. Multiple CVMs, bilateral orbital CVMs, and acute presentations are rare. We present a rare, bilateral, orbital CVM with acute painful visual loss in the left eye. The initial clinical presentation mimicked an idiopathic orbital inflammation. Orbital magnetic resonance imaging revealed its rare location at the left orbital apex. Finally, pathology confirmed the presence of an intralesional hemorrhage of a CVM.

HLA-DRB1 allele and autoantibody profiles in Japanese patients with inclusion body myositis.

INTRODUCTION: Inclusion body myositis (IBM) is an idiopathic inflammatory myopathy, characterized by unique clinical features including finger flexor and quadriceps muscle weakness and a lack of any reliable treatment. The human leukocyte antigen (HLA)-DRB1 allele and autoantibody profiles in Japanese IBM patients have not been fully elucidated. METHODS: We studied 83 Japanese IBM patients with a mean age of 69 years (49 males and 34 females) who participated in the 'Integrated Diagnosis Project for Inflammatory Myopathies' from January 2011 to September 2016. IBM was diagnosed by histological diagnosis. Various autoantibodies were screened by RNA immunoprecipitation and enzyme-linked immunosorbent assays. HLA-DRB1 genotyping was performed using polymerase chain reaction-sequence based typing. A total of 460 unrelated healthy Japanese controls were also studied. RESULTS: The allele frequencies of DRB1*01:01, DRB1*04:10, and DRB1*15:02 were significantly higher in the IBM group than in the healthy control group (Corrected P = 0.00078, 0.00038 and 0.0046). There was a weak association between the DRB1*01:01 allele and severe leg muscle weakness and muscle atrophy. While hepatitis type C virus infection and autoantibodies to cytosolic 5'-nucleotidase 1A were found in 18 and 28 patients, respectively, no significant association with HLA-DRB1 alleles was observed. CONCLUSION: Japanese IBM patients had the specific HLA-DRB1 allele and autoantibody profiles.