The Etiopathogenesis and Genetic Factors in Idiopathic Inflammatory Myopathies: A Review Article

Gustavo-Esteban Lugo-Zamudio1, *, Rosa-Elda Barbosa-Cobos2, Lucía-Verónica Maya-Piña2, Dolores Delgado-Ochoa3, María-Mercedes López-Mayorga2, Ivonne Arenas-Silva2, Diana-Sarai Arellano-Álvarez4
1 General Direction, Hospital Juárez de México, Mexico City, Mexico
2 Department of Rheumatology, Hospital Juárez de México, Mexico City, Mexico
3 Histocompatibility laboratory, Research Unit, Hospital Juárez de México, Mexico City, Mexico
4 Clinical laboratory, Hospital Juárez de México, Mexico City, Mexico

Article Metrics

CrossRef Citations:
Total Statistics:

Full-Text HTML Views: 242
Abstract HTML Views: 227
PDF Downloads: 118
ePub Downloads: 66
Total Views/Downloads: 653
Unique Statistics:

Full-Text HTML Views: 137
Abstract HTML Views: 92
PDF Downloads: 104
ePub Downloads: 56
Total Views/Downloads: 389

Creative Commons License
© 2023 Lugo-Zamudio et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Av. Instituto Politécnico Nacional, 5160 Col. Magdalena de las Salinas, Alcaldía Gustavo A. Madero C.P. 06770, Ciudad de México, México; E-mail:



Idiopathic inflammatory myopathies (IIM) are a group of heterogeneous systemic autoimmune diseases characterized by muscle inflammation from unknown causes resulting in chronic weakness. Recent studies have shown the role of the cellular immune response affecting muscle fibers in polymyositis (PM), inclusion body myositis, and to a lesser extent, dermatomyositis (DM), wherein humoral immunity is more involved. The value of genetic factors of the class II major histocompatibility complex (MHC II) has also been highlighted. In studies of murine models, the presence of HLA-DR3 favors a higher risk of developing inflammatory muscle disease, including PM and juvenile DM. In recent years, few studies have provided timely information regarding this, thus the researchers initially proposed a review of existing literature to broaden the context regarding what was described and to visualize proposals that may enhance the understanding of this group of inflammatory pathologies.


The design, implementation, analysis, and reporting of this study were followed according to the search with MeSH terms (Autoimmune myopathy, Inflammatory myopathies, Idiopathic inflammatory myopathies AND Major histocompatibility complex and genetics). We analyzed 12 articles for this review article.


In the etiopathogenesis of IIM, both humoral and cellular immunity are observed, considering the presence of a trigger that causes the immune response. As for the immunogenetics, this review highlights what has been reported in Chinese and Mexican populations, where HLADRB1*09:01 is related to the presence of DM, and is observed as the first variant identified in various populations. This increases interest in this allele in the particular case to study DM and strengthens research that proposes the study of IIM independently for each nosological entity.

Keywords: Autoimmune myopathy, Dermatomyositis, Inflammatory myopathies, Idiopathic inflammatory myopathies, Major histocompatibility complex, Myositis, Myositis idiopathic.


Idiopathic inflammatory myopathies (IIM) are a group of heterogeneous systemic autoimmune diseases characterized by muscle inflammation from unknown causes resulting in chronic weakness. Different causes and pathogenic mechanisms are responsible for inflammation and muscle damage; infectious agents, vaccines, neoplasms, drugs, and some immunological abnormalities, both cellular and humoral, have been considered in etiopathogenesis. Recent studies have highlighted the role of the cellular immune response in the affectation of muscle fibers in polymyositis, inclusion body myositis, and to a lesser degree, dermatomyositis, wherein there is greater humoral immunity involvement [1-4].

Two observations have supported the hypothesis that IIM are autoimmune disorders. The first is the association with other autoimmune diseases, including Hashimoto's thyroiditis, Graves' disease, myasthenia gravis, type I diabetes mellitus, primary biliary cholangitis, and connective tissue diseases [5-8]. The second is the high prevalence of circulating autoantibodies [9-14]. Histopathological findings in the striated muscle of patients with inflammatory myopathies have discovered the involvement of several pathologic mechanisms. These include microangiopathies and muscle ischemia, as well as inflammatory infiltration of the endomysium, mostly by B lymphocytes but also by CD4+ T cells and macrophages. This emphasizes the involvement of the humoral immune response in dermatomyositis (DM) [15-18].

It also highlights the importance of genetic factors located in the immune histocompatibility class II antigen [19, 20]. This has been demonstrated in studies of murine models, where the presence of HLA-DR3 favors an increased risk of developing inflammatory muscle disease, including polymyositis (PM) and juvenile DM. Similarly, the presence of anti-Jo-1 antibodies and HLA-DR52 appears to be correlated; there is also a reported association between HLA-DR1, DR6, and DQ1 and inclusion body myositis [21-25]. These elements together provide valuable data on immunogenetic, cellular, and humoral lines in the development of inflammatory myositis that allow for a better understanding of the genesis of IIM [26-28]. However, more studies are required to expand these concepts and validate the results, in addition to identifying possible population variants. In recent years, few studies have provided timely information regarding this. Therefore, this study initially proposed a review of the published literature to broaden the context of what has been described and to visualize proposals that allow for a better understanding of this group of inflammatory pathologies.

Idiopathic inflammatory myopathies are classified according to the EULAR/ACR (European League Against Rheumatism)/(American College of Rheumatology) in Dermatomyositis (DM), Amyopathic Dermatomyositis (ADM), Polymyositis (PM) and Inclusion Body Myositis (IBM) [29]. Recently, IIM was related to clinical manifestations and specific antibodies according to phenotypic, biological and immunological criteria that describe subgroups and established risk factors for mortality [30-32].

The genetic relationship of IIM is variable and depends on the age group; in the European population, it was identified that the heritability ranges from 22-24% for first-degree relatives and siblings, the family risk of Systemic Lupus Erythematosus and Rheumatoid Arthritis is higher in patients with Dermatomyositis or Polymyositis. The genes involved in the innate and adaptive immune response beyond the HLA region are STATA 4 (signal transducer and activator of transcription 4), TRAF6 (TNF receptor associated factor 6) and PTPN22 (Protein Tyrosine Phosphatase Non- Receiver Type 22). PTPN22 and STAT4 affect T-cell signaling, while TRAF6 affects B-cell and nuclear factor kappa-β (NF-κB) signaling [33-35].

Other pathogenic mechanisms include the NLRP3/caspase-1/IL-1β axis because it induces the class I Major Histocompatibility Complex in PM, and invitro, its inhibition reduces the expression of IL-1β and MHC-I, and the use of IL-1β neutralizing monoclonal antibody decreases muscle enzymes and C-reactive protein, and for this reason, it proposed a therapeutic target in PM [36-38]. On the another hand, complement involvement has been demonstrated in studies in patients with Juvenile Dermatomyositis (JDM). C4A deficiency is a genetic risk factor for patients with HLA*DR [39], and patients with anti-Jo antibodies or anti-Pm/ScL have lower plasma concentrations of complement [40].

In Dermatomyositis, some associated antibodies are posited to establish: anti-Mi-2, anti-TIF-1, anti-NXP2, anti-SAE y anti-MDA-5 [41]. Currently, phenotypes of Dermatomyositis associated with the anti-MDA-5 antibody are described as a systemic syndrome different from other patients with myositis, 3 subgroups with manifestations from mild to severe and variable prognosis [42-44]. The genetic component is related to nucleotide polymorphisms (SNP) in the Major Histocompatibility Complex (MHC) and with others outside the HLA, without differences according to gender or age [45].

The association of antibodies in the Caucasian population suggests that HLA DRB1*0301 is associated with anti-Jo-1 y anti-PL-12 antibodies, and in the African-American population, the antibody anti-Mi-2 is associated with HLA DRB1*0302 [46, 47].

HLA-DRB1 is associated with the specific anti-MDA-5 antibody in patients with DM in the population of Japan. The signal transducer and activator of the transcription 4 (STAT4) gene is related to some autoimmune diseases such as Systemic Lupus Erythematosus. STAT 4 is a transcription factor to trigger Th1 and Th17 responses, considering a risk factor for the development of IIM [48]. There is evidence of the genetic association with environmental factors such as smoking with HLA-DRB1*03 and anti-histidyl tRNA synthetase, on the other hand, HLA-DRB1*11:01 and statins for the development of anti-histidyl tRNA synthetase antibodies [49].

Myositis specific autoantibodies (MSAs) associated with genetic factors are: HLA-DRB1*12:02 associated with anti-MDA5, HLA-DRB1*14:03 with anti-SRP, HLA-DRB1*07:01 with anti-Mi-2, HLA-DRB1* 13:01 with anti-TIF1γ [18], and HLA-DRB1*11:01 with anti-Hydroxy methyl glutaryl coenzyme A reductase antibody [50].

In inclusion body myositis (IBM), genetic factors may influence susceptibility to disease. The strongest association is with amino acids 26 and 11 of the HLA-DRB1 molecule [51-53]. In muscle biopsies, inflammatory and degenerative alterations are found; there is inflammation of the endomysium and positive regulation of the class I MHC. Degenerative aspects include the formation of tubulofilamentous vacuoles seen in electron microscopy, mitochondrial changes and deposition of myotoxic proteins such as amyloid p62 and DNA-binding protein TAR-43 (TDP-43) [54].


2.1. Search Method

The design, implementation, analysis, and reporting of this study were followed according to the search with MeSH terms. We analyzed observational studies that were published from February 10, 2014 to December 08, 2020, using the following terms in titles, abstracts, and keywords: myositis, idiopathic myositis, inflammatory myopathies, idiopathic inflammatory myopathies, dermatomyositis, autoimmune myopathy, genetics and HLA. The literature search was not subject to language restrictions. The retrieved literature was reviewed for the following criteria: Patients over 18 years of age, diagnosis of IIM according to Bohan and Peter’s criteria, observational genetic characterization studies evaluating the association of HLA and MII (DM and PM subtypes) were considered, the study of cases and controls and years of publication since February 2014 to December 2020.


We identified twelve articles that were thus selected for full-text analysis. Table 1 shows the studies that were included in the review. All the material was published during the search period.


Among the findings described in several publications, microangiopathy and muscle ischemia, together with inflammatory infiltrates composed mainly of B lymphocytes [62-64], and smaller proportions of CD4+ T cells and macrophages in the endomysium suggest that the participation of the humoral immune response is crucial in DM. Moreover, the activation of the complement membrane attack complex C5b-9 is an early element of utmost importance that triggers the release of pro-inflammatory cytokines and chemokines by endothelial cells. [65-67] These facilitate the migration of activated lymphocytes to the perimysial and endomysial spaces, resulting in necrosis of endothelial cells and a decrease in the number of endomysial capillaries, as well as ischemia and destruction of muscle fibers like those found in microinfarcts [68-70]. Another important finding is the response observed in capillaries “unaffected by the inflammatory process” that usually show dilation of their inner diameter in reactivity to the ischemic picture [71-77].

Polymyositis and inclusion body myopathy (IBM), T-lymphocyte-mediated cytotoxicity and necroptosis are the predominant pathogenic mechanisms. [78, 79] Initially, CD8+ T lymphocytes and macrophages surround, invade, and destroy healthy non-necrotic muscle fibers, and cytokines are produced apoptosis that induce overexpression of MHC class I (MHC-I) molecules [80-82]. The CD8/MHC-I complex is a characteristic of these two diseases, and its detection has become necessary to confirm the histological diagnosis. [83-86] Cytotoxic CD8+ T lymphocytes contain perforin and granzyme granules targeted against the surface of muscle fibers and are capable of inducing muscle cell necrosis [56].

Table 1.
Articles included for review.
Author, Year Type Population Outcome Remarks
Gao X, et al. (2014) [ 55] Cases and controls Chinese HLA susceptibility DM and PM HLA and DM association
Miller F, et al. (2015) [52] Cases and controls Caucasians HLA and phenotype correlation HLA 8.1 defines the genetic risk of the MII phenotype
Rothwell S, et al. (2016) [56] Cases and controls Caucasians Association of HLA susceptibility to MII No differences were found in the overall analysis, but differences were found in the analysis by subgroups
Zhang CE, et al. (2016) [57] Cases and controls Chinese HLA susceptibility DM HLA SNP associated with DM
Lin JM, et al. (2017) [23] Cases and controls Chinese HLA and pathogenesis of DM HLA associated with DM
Chen Z, et al. (2017) [58] Cases and controls Chinese HLA and susceptibility to anti-MDA5 in DM HLA, Anti-MDA5, ILD and DM association
Houtman M, et al. (2018) [2] Cases and controls Swedes T cell, HLA and association of PM/DM PM and DM are two clinical phenotypes that differ in T-cell phenotypes related to gene expression
Peng QL, et al. (2018) [13] Cases and controls Caucasians HLA Susceptibility to MII HLA association with AS.

Other pathogenic mechanisms, such as the interferon signature, have been analyzed [87-89]. The expression of IFN α and β inducible genes was high in DM, moderate in antisynthetase syndrome (AS), and low in IBM. In contrast, the expression of IFN γ inducible genes was high in IBM; these differences propose potential therapeutic targets [90]. Class I and II MHC upregulation is an early finding in the skeletal muscle in PM; IFN-γ transcript expression has been shown up-regulated in PM muscle compared to other IIM and involved in the induction of MHC class II molecules. [91-93].

Human leukocyte antigen (HLA) genetic variability is crucial in the pathogenesis of DM and PM; this may be attributed in part to the influence of HLA molecules on T-cell receptor development, peripheral tolerance, and immune response to environmental agents. It has been established that geographic location and ethnicity may affect susceptibility to autoimmune disease; HLA-DRB1*03:01 and HLA-DQA1*05:01 alleles have been described as risk factors for myositis in Western populations [71, 72], while DRB1*08:03 may increase PM susceptibility among the Japanese population. [2, 6, 15, 62] DRB1*01:01, DRB1*04:10, and DRB1*15:02 were high in the Japanese patients with IBM [19, 94]. In other populations in northern China, positive associations between HLA-DRB1*04, HLA-DRB1*07, and HLA-DRB1*12 and the development of DM have been reported, while HLA-DQB1*04:01 [26, 27] is a risk factor for both DM and PM in this same population. Studies also show that HLA class II alleles may influence DM and PM susceptibility of adults in the Han Chinese population [2], particularly HLA-DRB1*09:01 and HLA-DRB1*12:01 [14, 16-18].

Furthermore, three studies involving the Mexican population have been published on the association of IIM and HLA. In 1996, Arnett F found no association between HLA alleles and susceptibility to present IIM [6]. Subsequently, Ejaz A. Shamim et al. described the association of different HLA-DRB1 and DQA1 with anti-Mi-2 antibodies [73]. In 2018, Lugo G. et al. also reported positive and negative associations between HLA polymorphisms and DM subtypes and found that HLA-A*01:01, HLA-A*03:01, HLA-B*07:02, HLA-DRB1*01:02, and HLADRB1*09:01 are significantly associated with susceptibility to this disease, the latter being similar to that reported in the Chinese population [8, 12]. Meanwhile, DRB1*16:01 and DQB1* 03:02 alleles are considered protective factors in the Mexican population [12].


In the etiopathogenesis of IIM, the participation of different mechanisms is observed, involving humoral and cellular immunity, following an underlying trigger that would set off the immune response. The immunogenetic participation highlights the presence of HLA DRB1*09:01 in Chinese and Mexican populations, wherein it is related to the presence of DM in both studies, and is observed as the first variant identified in different populations. Therefore, interest in this allele in the case of this myopathy is increased. The independent study of the different diseases encompassed by IIM is also strengthened since no results identifying similar alleles associated with the presentation of IIM as a whole in different populations have been identified, unlike the evidence documented regarding DM.


Dr. Gustavo Esteban Lugo Zamudio, Rosa Elda Barbosa Cobos, and Lucia Verónica Maya Piña contributed to the coordination of the project, analysis of the information and structure of the manuscript.

Dr. María Mercedes López Mayorga, Ivonne Arenas Silva and Diana Sarai Arellado Álvarez contributed to the search for scientific information and review of case information.

Magister Scientiae Dolores Delgado Ochoa contributed to histocompatibility tests.


ACR = American College of Rheumatology
ADM Amyopathic Dermatomyositis
AS = Antisynthetase Syndrome
DM = Dermatomyositis
EULAR = European League Against Rheumatism
HLA = Human Leukocyte Antigen
IIM = Idiopathic Inflammatory Myopathies
IBM = Inclusion Body Myopathy
JDM = Juvenile Dermatomyositis
MCH = Major Histocompatibility Complex
MSAs = Myositis Specific Autoantibodies
PM = Polymyositis
PTPN22 = Protein Tyrosine Phosphatase Non- Receiver Type 22
STATA 4 = Signal Transducer and Activator of Transcription 4
TRAF6 = TNF Receptor Associated Factor 6


Not applicable.


We confirm that the data supporting the findings of this study are available within the article and its supplementary materials.




The author declares no conflict of interest, financial or otherwise.


Declared none.


[1] Rider LG, Aggarwal R, Machado PM, et al. Update on outcome assessment in myositis. Nat Rev Rheumatol 2018; 14(5): 303-18.
[2] Houtman M, Ekholm L, Hesselberg E, et al. T-cell transcriptomics from peripheral blood highlights differences between polymyositis and dermatomyositis patients. Arthritis Res Ther 2018; 20(1): 188.
[3] Schiffenbauer A, Faghihi-Kashani S, O’Hanlon TP, et al. The effect of cigarette smoking on the clinical and serological phenotypes of polymyositis and dermatomyositis. Semin Arthritis Rheum 2018; 48(3): 504-12.
[4] Mandel D, Malemud C, Askari A. Idiopathic inflammatory myopathies: A review of the classification and impact of pathogenesis. Int J Mol Sci 2017; 18(5): 1084.
[5] Lundberg IE, de Visser M, Werth VP. Classification of myositis. Nat Rev Rheumatol 2018; 14(5): 269-78.
[6] Krassas GE, Wiersinga W. Smoking and autoimmune thyroid disease: The plot thickens. Eur J Endocrinol 2006; 154(6): 777-80.
[7] McHugh NJ, Tansley SL. Autoantibodies in myositis. Nat Rev Rheumatol 2018; 14(5): 290-302.
[8] Perricone C, Versini M, Ben-Ami D, et al. Smoke and autoimmunity: The fire behind the disease. Autoimmun Rev 2016; 15(4): 354-74.
[9] Miller FW. Non-infectious environmental agents and autoimmunity. Autoimmune Dis 2014; 283-95.
[10] Mahid SS, Minor KS, Soto RE, Hornung CA, Galandiuk S. Smoking and inflammatory bowel disease: A meta-analysis. Mayo Clin Proc 2006; 81(11): 1462-71.
[11] Chinoy H, Adimulam S, Marriage F, et al. Interaction of HLA-DRB1*03 and smoking for the development of anti-Jo-1 antibodies in adult idiopathic inflammatory myopathies: A European-wide case study. Ann Rheum Dis 2012; 71(6): 961-5.
[12] Colafrancesco S, Priori R, Valesini G. Inflammatory myopathies and overlap syndromes: Update on histological and serological profile. Best Pract Res Clin Rheumatol 2015; 29(6): 810-25.
[13] Remuzgo-Martínez S, Atienza-Mateo B, Ocejo-Vinyals JG, et al. HLA association with the susceptibility to anti-synthetase syndrome. Joint Bone Spine 2021; 88(3): 105115.
[14] Riebeling-Navarro C, Nava A. Pathogenesis of idiopathic inflammatory myopathies. Reumatol Clin 2009; 5(Suppl. 3): 6-8.
[15] Dalakas MC. Muscle biopsy findings in inflammatory myopathies. Rheum Dis Clin North Am 2002; 28(4): 779-798, vi.
[16] Callen JP. Dermatomyositis. Lancet 2000; 355(9197): 53-7.
[17] Tournadre A, Lenief V, Miossec P. Expression of Toll-like receptor 3 and Toll-like receptor 7 in muscle is characteristic of inflammatory myopathy and is differentially regulated by Th1 and Th17 cytokines. Arthritis Rheum 2010; 62(7): 2144-51.
[18] Kang EH, Go DJ, Mimori T, et al. Novel susceptibility alleles in HLA region for myositis and myositis specific autoantibodies in Korean patients. Semin Arthritis Rheum 2019; 49(2): 283-7.
[19] Oyama M, Ohnuki Y, Inoue M, et al. HLA-DRB1 allele and autoantibody profiles in Japanese patients with inclusion body myositis. PLoS One 2020; 15(8): e0237890.
[20] Zamudio GL, Barbosa Cobos RE, Solorzano Ruiz A, Morales EL, DelgadoOchoa D. HLA class I and II alleles may influence susceptibility to adult dermatomyositis in a Mexican mestizo population. Int J Clin Rheumatol 2018; 13(2): 71-81.
[21] Wu Q, Wedderburn LR, McCann LJ. Juvenile dermatomyositis: Latest advances. Best Pract Res Clin Rheumatol 2017; 31(4): 535-57.
[22] Miller FW, Lamb JA, Schmidt J, Nagaraju K. Risk factors and disease mechanisms in myositis. Nat Rev Rheumatol 2018; 14(5): 255-68.
[23] Lin JM, Zhang YB, Peng QL, et al. Genetic association of HLA-DRB1 multiple polymorphisms with dermatomyositis in Chinese population. HLA 2017; 90(6): 354-9.
[24] Rothwell S, Lamb JA, Chinoy H. New developments in genetics of myositis. Curr Opin Rheumatol 2016; 28(6): 651-6.
[25] Rothwell S, Lilleker JB, Lamb JA. Genetics in inclusion body myositis. Curr Opin Rheumatol 2017; 29(6): 639-44.
[26] Flåm ST, Gunnarsson R, Garen T, Lie BA, Molberg Ø. The HLA profiles of mixed connective tissue disease differ distinctly from the profiles of clinically related connective tissue diseases. Rheumatology 2015; 54(3): 528-35.
[27] Sugiura T, Kawaguchi Y, Goto K, et al. Association between a C8orf13-BLK polymorphism and polymyositis/dermatomyositis in the Japanese population: An additive effect with STAT4 on disease susceptibility. PLoS One 2014; 9(3): e90019.
[28] Zhu B, Yang G, Shen C, et al. Distributions of HLA-A and -B alleles and haplotypes in the Yi ethnic minority of Yunnan, China: relationship to other populations. J Zhejiang Univ Sci B 2010; 11(2): 127-35.
[29] Bottai M, Tjärnlund A, Santoni G, et al. EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups: A methodology report. RMD Open 2017; 3(2): e000507.
[30] Zheng S, Chen S, Wu L, et al. Classification of idiopathic inflammatory myopathies based on clinical manifestations and myositis-specific antibodies. Nan Fang Yi Ke Da Xue Xue Bao 2020; 40(7): 1029-35.
[31] Alenzi F. Myositis specific autoantibodies: A clinical perspective. Open Access Rheumatol 2020; 12: 9-14.
[32] Mariampillai K, Granger B, Amelin D, et al. Development of a new classification system for idiopathic inflammatory myopathies based on clinical manifestations and myositis-specific autoantibodies. JAMA Neurol 2018; 75(12): 1528-37.
[33] Lamb JA. The genetics of autoimmune myositis. Front Immunol 2022; 13: 886290.
[34] Che WI, Westerlind H, Lundberg IE, Hellgren K, Kuja-Halkola R, Holmqvist M. Familial aggregation and heritability: A nationwide family-based study of idiopathic inflammatory myopathies. Ann Rheum Dis 2021; 80(11): 1461-6.
[35] Thomsen H, Li X, Sundquist K, Sundquist J, Försti A, Hemminki K. Familial associations for rheumatoid autoimmune diseases. Rheumatol Adv Pract 2020; 4(2): rkaa048.
[36] Xia P, Shao YQ, Yu CC, Xie Y, Zhou ZJ. NLRP3 inflammasome up-regulates major histocompatibility complex class I expression and promotes inflammatory infiltration in polymyositis. BMC Immunol 2022; 23(1): 39.
[37] Kong R, Sun L, Li H, Wang D. The role of NLRP3 inflammasome in the pathogenesis of rheumatic disease. Autoimmunity 2022; 55(1): 1-7.
[38] You R, He X, Zeng Z, Zhan Y, Xiao Y, Xiao R. Pyroptosis and its role in autoimmune disease: A potential therapeutic target. Front Immunol 2022; 13: 841732.
[39] Lintner KE, Patwardhan A, Rider LG, et al. Gene copy-number variations (CNVs) of complement C4 and C4A deficiency in genetic risk and pathogenesis of juvenile dermatomyositis. Ann Rheum Dis 2016; 75(9): 1599-606.
[40] Zhou D, King EH, Rothwell S, et al. for MYOGEN Investigators. Low copy numbers of complement C4 and C4A deficiency are risk factors for myositis, its subgroups and autoantibodies. Ann Rheum Dis 2022; 1-11.
[41] Bolko L, Gitiaux C, Allenbach Y. Dermatomyosites Nouveaux anticorps, nouvelle classification. Med Sci 2019; 35(2): 18-23.
[42] Allenbach Y, Uzunhan Y, Toquet S, et al. Different phenotypes in dermatomyositis associated with anti-MDA5 antibody. Neurology 2020; 95(1): e70-8.
[43] Yang Q, Lyu K, Li J, et al. Anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis exhibit three clinical phenotypes with different prognoses. Clin Exp Rheumatol 2022; 40(2): 304-8.
[44] Collado MV, Gargiulo MLÁ, Gómez R, et al. Dermatomiositis asociada al autoanticuerpo anti-MDA5. Medicina 2018; 78(5): 360-3.
[45] Miller FW, Cooper RG, Vencovský J, et al. Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders. Arthritis Rheum 2013; 65(12): 3239-47.
[46] Chinoy H, Lamb JA, Ollier WER, Cooper RG. Recent advances in the immunogenetics of idiopathic inflammatory myopathy. Arthritis Res Ther 2011; 13(3): 216.
[47] Shamim EA, Rider LG, Miller FW. Update on the genetics of the idiopathic inflammatory myopathies. Curr Opin Rheumatol 2000; 12(6): 482-91.
[48] Rothwell S, Cooper RG, Lamb JA, Chinoy H. Strategies for evaluating idiopathic inflammatory myopathy disease susceptibility genes. Curr Rheumatol Rep 2014; 16(10): 446.
[49] Rothwell S, Cooper RG, Lamb JA, Chinoy H. Entering a new phase of immunogenetics in the idiopathic inflammatory myopathies. Curr Opin Rheumatol 2013; 25(6): 735-41.
[50] Mammen AL, Gaudet D, Brisson D, et al. Increased frequency of DRB1*11:01 in anti-hydroxymethylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Arthritis Care Res 2012; 64(8): 1233-7.
[51] Rothwell S, Cooper RG, Lundberg IE, et al. Immune‐array analysis in sporadic inclusion body myositis reveals HLA–DRB1 amino acid heterogeneity across the myositis spectrum. Arthritis Rheumatol 2017; 69(5): 1090-9.
[52] Miller FW, Chen W, O’Hanlon TP, et al. Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as major genetic risk factors for myositis phenotypes. Genes Immun 2015; 16(7): 470-80.
[53] Rojana-udomsart A, James I, Castley A, et al. High-resolution HLA-DRB1 genotyping in an Australian inclusion body myositis (s-IBM) cohort: An analysis of disease-associated alleles and diplotypes. J Neuroimmunol 2012; 250(1-2): 77-82.
[54] Gang Q, Bettencourt C, Machado P, Hanna MG, Houlden H. Sporadic inclusion body myositis: The genetic contributions to the pathogenesis. Orphanet J Rare Dis 2014; 9(1): 88.
[55] Gao X, Han L, Yuan L, et al. HLA class II alleles may influence susceptibility to adult dermatomyositis and polymyositis in a Han Chinese population. BMC Dermatol 2014; 14(1): 9.
[56] Rothwell S, Cooper RG, Lundberg IE, et al. Dense genotyping of immune-related loci in idiopathic inflammatory myopathies confirms HLA alleles as the strongest genetic risk factor and suggests different genetic background for major clinical subgroups. Ann Rheum Dis 2016; 75(8): 1558-66.
[57] Zhang CE, Li Y, Wang ZX, et al. Variation at HLA-DPB1 is associated with dermatomyositis in Chinese population. J Dermatol 2016; 43(11): 1307-13.
[58] Chen Z, Wang Y, Kuwana M, et al. HLA-DRB1 alleles as genetic risk factors for the development of anti-MDA5 antibodies in patients with dermatomyositis. J Rheumatol 2017; 44(9): 1389-93.
[59] Peng QL, Lin JM, Zhang YB, et al. Targeted capture sequencing identifies novel genetic variations in Chinese patients with idiopathic inflammatory myopathies. Int J Rheum Dis 2018; 21(8): 1619-26.
[60] Parkes JE, Rothwell S, Oldroyd A, Chinoy H, Lamb JA. Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis. Arthritis Res Ther 2018; 20(1): 117.
[61] Rothwell S, Chinoy H, Lamb JA, et al. Focused HLA analysis in Caucasians with myositis identifies significant associations with autoantibody subgroups. Ann Rheum Dis 2019; 78(7): 996-1002.
[62] Coutant F, Bachet R, Pin JJ, Alonzo M, Miossec P. Monoclonal antibodies from B cells of patients with anti-MDA5 antibody-positive dermatomyositis directly stimulate interferon gamma production. J Autoimmun 2022; 130: 102831.
[63] Tang Q, Ramsköld D, Krystufkova O, et al. Effect of CTLA4‐Ig (abatacept) treatment on T cells and B cells in peripheral blood of patients with polymyositis and dermatomyositis. Scand J Immunol 2018; 89(1): e12732.
[64] Aggarwal R, Oddis CV, Goudeau D, et al. Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab. Rheumatology 2016; 55(6): 991-9.
[65] Cong L, Pu CQ, Shi Q, Wang Q, Lu XH. Complement membrane attack complex is related with immune-mediated necrotizing myopathy. Int J Clin Exp Pathol 2014; 7(7): 4143-9.
[66] Duchesne M, Leonard-Louis S, Landon-Cardinal O, et al. Edematous myositis: A clinical presentation first suggesting dermatomyositis diagnosis. Brain Pathol 2020; 30(5)
[67] Milisenda JC, Doti PI, Prieto-González S, Grau JM. Dermatomyositis presenting with severe subcutaneous edema: Five additional cases and review of the literature. Semin Arthritis Rheum 2014; 44(2): 228-33.
[68] Yasin SA, Schutz PW, Deakin CT, et al. Histological heterogeneity in a large clinical cohort of juvenile idiopathic inflammatory myopathy: Analysis by myositis autoantibody and pathological features. Neuropathol Appl Neurobiol 2019; 45(5): 495-512.
[69] Song J, Kim D, Hong J, et al. Meta-analysis of polymyositis and dermatomyositis microarray data reveals novel genetic biomarkers. Genes 2019; 10(11): 864.
[70] Liu W, Zhao WJ, Wu YH. Study on the differentially expressed genes and signaling pathways in dermatomyositis using integrated bioinformatics method. Medicine 2020; 99(34): e21863.
[71] O’Hanlon TP, Carrick DM, Targoff IN, et al. Immunogenetic risk and protective factors for the idiopathic inflammatory myopathies: distinct HLA-A, -B, -Cw, -DRB1, and -DQA1 allelic profiles distinguish European American patients with different myositis autoantibodies. Medicine 2006; 85(2): 111-27.
[72] Arnett FC, Targoff IN, Mimori T, Goldstein R, Warner NB, Reveille JD. Interrelationship of major histocompatibility complex class II alleles and autoantibodies in four ethnic groups with various forms of myositis. Arthritis Rheum 1996; 39(9): 1507-18.
[73] Shamim EA, Rider LG, Pandey JP, et al. Differences in idiopathic inflammatory myopathy phenotypes and genotypes between Mesoamerican Mestizos and North American Caucasians: Ethnogeographic influences in the genetics and clinical expression of myositis. Arthritis Rheum 2002; 46(7): 1885-93.
[74] Cavalli S, Lonati PA, Gerosa M, Caporali R, Cimaz R, Chighizola CB. Beyond systemic lupus erythematosus and anti-phospholipid syndrome: the relevance of complement from pathogenesis to pregnancy outcome in other systemic rheumatologic diseases. Front Pharmacol 2022; 13: 841785.
[75] Carstens PO, Schmidt J. Diagnosis, pathogenesis and treatment of myositis: Recent advances. Clin Exp Immunol 2014; 175(3): 349-58.
[76] Baig S, Paik JJ. Inflammatory muscle disease-an update. Best Pract Res Clin Rheumatol 2020; 34(1): 101484.
[77] Tanboon J, Nishino I. Classification of idiopathic inflammatory myopathies: Pathology perspectives. Curr Opin Neurol 2019; 32(5): 704-14.
[78] Kamiya M, Mizoguchi F, Kawahata K, et al. Targeting necroptosis in muscle fibers ameliorates inflammatory myopathies. Nat Commun 2022; 13(1): 166.
[79] Kamiya M, Mizoguchi F, Takamura A, Kimura N, Kawahata K, Kohsaka H. A new in vitro model of polymyositis reveals CD8+ T cell invasion into muscle cells and its cytotoxic role. Rheumatology 2020; 59(1): 224-32.
[80] Danielsson O, Häggqvist B, Gröntoft L, Öllinger K, Ernerudh J. Apoptosis in idiopathic inflammatory myopathies with partial invasion; a role for CD8+ cytotoxic T cells? PLoS One 2020; 15(9): e0239176.
[81] Peng QL, Zhang YM, Liu YC, et al. Contribution of necroptosis to myofiber death in idiopathic inflammatory myopathies. Arthritis Rheumatol 2022; 74(6): 1048-58.
[82] Shu X, Chen F, Peng Q, et al. Potential role of autophagy in T-cell survival in polymyositis and dermatomyositis. Mol Med Rep 2017; 16(2): 1180-8.
[83] Nagy S, Khan A, Machado PM, Houlden H. Inclusion body myositis: From genetics to clinical trials. J Neurol 2022; 1-11.
[84] Snedden AM, Kellett KAB, Lilleker JB, Hooper NM, Chinoy H. The role of protein aggregation in the pathogenesis of inclusion body myositis. Clin Exp Rheumatol 2022; 40(2): 414-24.
[85] Huang PL, Hou MS, Wang SW, Chang CL, Liou YH, Liao NS. Skeletal muscle interleukin 15 promotes CD8+ T-cell function and autoimmune myositis. Skelet Muscle 2015; 5(1): 33.
[86] Zhang J, Khasanova E, Zhang L. Bioinformatics analysis of gene expression profiles of Inclusion body myositis. Scand J Immunol 2020; 91(6): e12887.
[87] Rigolet M, Hou C, Baba Amer Y, et al. Distinct interferon signatures stratify inflammatory and dysimmune myopathies. RMD Open 2019; 5(1): e000811.
[88] Bolko L, Jiang W, Tawara N, et al. The role of interferons type I, II and III in myositis: A review. Brain Pathol 2021; 31(3): e12955.
[89] Ll Wilkinson MG, Deakin CT, Papadopoulou C, Eleftheriou D, Wedderburn LR. JAK inhibitors: A potential treatment for JDM in the context of the role of interferon-driven pathology. Pediatr Rheumatol Online J 2021; 19(1): 146.
[90] Pinal-Fernandez I, Casal-Dominguez M, Derfoul A, et al. Identification of distinctive interferon gene signatures in different types of myositis. Neurology 2019; 93(12): e1193-204.
[91] Radziszewska A, Moulder Z, Jury EC, Ciurtin C. CD8+ T cell phenotype and function in childhood and adult-onset connective tissue disease. Int J Mol Sci 2022; 23(19): 11431.
[92] Atluri RB. Inflammatory myopathies. Mo Med 2016; 113(2): 127-30.
[93] Haq SA, Tournadre A. Idiopathic inflammatory myopathies: From immunopathogenesis to new therapeutic targets. Int J Rheum Dis 2015; 18(8): 818-25.
[94] Britson KA, Yang SY, Lloyd TE. New developments in the genetics of inclusion body myositis. Curr Rheumatol Rep 2018; 20(5): 26.