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1.
O'Hanlon TP Carrick DM Arnett FC Reveille JD Carrington M Gao X Oddis CV Morel PA Malley JD Malley K Dreyfuss J Shamim EA Rider LG Chanock SJ Foster CB Bunch T Plotz PH Love LA Miller FW 《Medicine》2005,84(6):338-349
The idiopathic inflammatory myopathies (IIM) are systemic connective tissue diseases in which autoimmune pathology is suspected to promote chronic muscle inflammation and weakness. We have performed low to high resolution genotyping to characterize the allelic profiles of HLA-A, -B, -Cw, -DRB1, and -DQA1 loci in a large population of North American Caucasian patients with IIM representing the major clinicopathologic groups (n = 571). We confirmed that alleles of the 8.1 ancestral haplotype were important risk markers for the development of IIM, and a random forests classification analysis suggested that within this haplotype, HLA-B*0801, DRB1*0301 and/ or closely linked genes are the principal HLA risk factors. In addition, we identified several novel HLA factors associated distinctly with 1 or more clinicopathologic groups of IIM. The DQA1*0201 allele and associated peptide-binding motif (KLPLFHRL) were exclusive protective factors for the CD8+ T cell-mediated IIM forms of polymyositis (PM) and inclusion body myositis (IBM) (pc < 0.005). In contrast, HLA-A*68 alleles were significant risk factors for dermatomyositis (DM) (pc = 0.0021), a distinct clinical group thought to involve a humorally mediated immunopathology. While the DQA1*0301 allele was detected as a possible risk factor for IIM, PM, and DM patients (p < 0.05), DQA1*03 alleles were protective factors for IBM (pc = 0.0002). Myositis associated with malignancies was the most distinctive group of IIM wherein HLA Class I alleles were the only identifiable susceptibility factors and a shared HLA-Cw peptide-binding motif (AGSHTLQWM) conferred significant risk (pc = 0.019). Together, these data suggest that HLA susceptibility markers distinguish different myositis phenotypes with divergent pathogenetic mechanisms. These variations in associated HLA polymorphisms may reflect responses to unique environmental triggers resulting in the tissue pathospecificity and distinct clinicopathologic syndromes of the IIM. 相似文献
2.
Vidya S. LIMAYE Sue LESTER Peter BLUMBERGS Peter J. ROBERTS‐THOMSON 《International journal of rheumatic diseases》2010,13(2):132-137
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. 相似文献
3.
Ya-Mei Zhang Han-Bo Yang Jing-Li Shi He Chen Xiao-Ming Shu Xin Lu Guo-Chun Wang Qing-Lin Peng 《Clinical rheumatology》2018,37(6):1573-1580
Autoantibodies against poly-U-binding factor 60 kDa protein (PUF60) have been reported in Caucasian dermatomyositis (DM) patients. However, their clinical significance in idiopathic inflammatory myopathy (IIM) remains to be fully clarified. Our objective was to analyze the prevalence and clinical significance of anti-PUF60 antibodies in a large cohort of Chinese IIM patients. In our study, 388 IIM patients, 301 disease controls, and 167 healthy controls (HCs) were involved. An enzyme-linked immunosorbent assay (ELISA) was developed to detect serum anti-PUF60 levels and was validated using immunoblotting methods. Unpaired Mann-Whitney U test and Spearman correlation analysis were used when appropriate. Anti-PUF60 antibodies were observed in IIM patients at a frequency of 10.6% (41/388). Subgrouping analysis revealed that the prevalence of anti-PUF60 antibodies was 10% in DM, 5.5% in polymyositis (PM), 10% in immune-mediated necrotizing myositis (IMNM), and 26.5% in myositis-overlap syndrome. Anti-PUF60 antibodies were also observed in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren’s syndrome (SS) patients at a positive rate of 17.3, 14.5, and 10.1% respectively. Intriguingly, anti-PUF60 antibodies were frequently observed in clinically amyopathic dermatomyositis (CADM) patients and DM patients without currently known myositis autoantibodies. Furthermore, DM patients with anti-PUF60 antibodies had higher prevalence of skin ulcerations. Moreover, longitudinal investigation in eight DM patients with anti-PUF60 antibodies revealed that the antibodies levels decreased with disease remission. Anti-PUF60 antibodies were nonspecific for myositis, since they could be detected in other rheumatic diseases. Further investigation of anti-PUF60 antibodies may reveal shared pathogenic pathways in systemic autoimmune disorders. 相似文献
4.
Frank C. Arnett Ira N. Targoff Tsuneyo Mimori Rose Goldstein Noranna B. Warner John D. Reveille 《Arthritis \u0026amp; Rheumatology》1996,39(9):1507-1518
Objective. To examine interrelationships among myositis subsets, autoantibodies, and major histocompatibility complex (MHC) class II alleles across ethnic lines, and to localize genetic susceptibility (presence of HLA–DR versus DQ) to myositis within the MHC class II region. Methods. MHC class II alleles (HLA–DRB1, DQA1, and DQB1, detected by DNA oligotyping) and myositis-specific autoantibodies (MSA) were determined in 224 patients with various myositis syndromes, including 89 whites, 89 African-Americans, 25 Mexican-Americans, and 21 Japanese. Results. Anti–Jo-1 (histidyl–transfer RNA [tRNA] synthetase) and other MSAs (anti–PL-12, anti–PL-7, anti-OJ, anti-EJ, anti-KJ, anti-tRNA, and anti–signal recognition particle) were equally distributed among the races, but occurred more often in patients with polymyositis (PM) than in those with dermatomyositis (DM) or other myositis syndromes. MSA frequencies were significantly positively associated with anti–Ro (SS-A) (P = 0.002), and significantly negatively associated with anti–U1 RNP (P = 0.003). Frequencies of the HLA–DRB1*0301 (DR3), DQA1*0501, and DQB1*0201 (DQ2) alleles (and haplotype) were each increased in white patients with myositis, especially those with PM, but most strikingly in those with MSAs. However, in the other ethnic groups, except the Japanese group, only frequencies of HLA–DQA1*0501 and the structurally similar DQA1*0401 alleles were significantly increased. The presence of HLA–DQA1*0501 or *0401 was most significantly associated with anti–Jo-1, anti–PL-12, and other MSAs, compared with myositis patients without MSAs (P = 0.0008, Pcorr = 0.01, odds ratio [OR] = 3.7), and with normal, ethnically matched controls (P = 3 × 10−7, Pcorr = 1 × 10−6, OR = 6.5). Among MSA-positive patients who were negative for HLA–DQA1*0501 and *0401, including Japanese patients, the HLA–DQA1*0101 and *0103 alleles predominated. In addition, there appeared to be a negative association of the HLA–DR2 alleles (DRB1*1501 and *1503) with PM (P = 0.007, Pcorr not significant, OR = 0.39), but not with DM or myositis overall. Conclusion. By transracial gene mapping, genetic susceptibility to anti–Jo-1 and other MSAs in patients with myositis can be localized within the MHC region to the HLA–DQA1 locus. 相似文献
5.
Brouwer R Hengstman GJ Vree Egberts W Ehrfeld H Bozic B Ghirardello A Grøndal G Hietarinta M Isenberg D Kalden JR Lundberg I Moutsopoulos H Roux-Lombard P Vencovsky J Wikman A Seelig HP van Engelen BG van Venrooij WJ 《Annals of the rheumatic diseases》2001,60(2):116-123
OBJECTIVE: To determine the prevalence of myositis specific autoantibodies (MSAs) and several myositis associated autoantibodies (MAAs) in a large group of patients with myositis. METHODS: A total of 417 patients with myositis from 11 European countries (198 patients with polymyositis (PM), 181 with dermatomyositis (DM), and 38 with inclusion body myositis (IBM)) were serologically analysed by immunoblot, enzyme linked immunosorbent assay (ELISA) and/or immunoprecipitation. RESULTS: Autoantibodies were found in 232 sera (56%), including 157 samples (38%) which contained MSAs. The most commonly detected MSA was anti-Jo-1 (18%). Other anti-synthetase, anti-Mi-2, and anti-SRP autoantibodies were found in 3%, 14%, and 5% of the sera, respectively. A relatively high number of anti-Mi-2 positive PM sera were found (9% of PM sera). The most commonly detected MAA was anti-Ro52 (25%). Anti-PM/Scl-100, anti-PM/Scl-75, anti-Mas, anti-Ro60, anti-La, and anti-U1 snRNP autoantibodies were present in 6%, 3%, 2%, 4%, 5%, and 6% of the sera, respectively. Remarkable associations were noticed between anti-Ro52 and anti-Jo-1 autoantibodies and, in a few sera, also between anti-Jo-1 and anti-SRP or anti-Mi-2 autoantibodies. CONCLUSIONS: The incidence of most of the tested autoantibody activities in this large group of European patients is in agreement with similar studies of Japanese and American patients. The relatively high number of PM sera with anti-Mi-2 reactivity may be explained by the use of multiple recombinant fragments spanning the complete antigen. Furthermore, our data show that some sera may contain more than one type of MSA and confirm the strong association of anti-Ro52 with anti-Jo-1 reactivity. 相似文献
6.
M. Hirakata 《Modern rheumatology / the Japan Rheumatism Association》2000,10(4):199-206
Evidence of the involvement of systemic autoimmunity has been observed in polymyositis/dermatomyositis (PM/DM). Autoantibodies
directed against various cellular constituents have been detected in most patients with PM/DM, and about one-third of patients
have autoantibodies (myositis-specific antibodies: MSAs) that are found specifically in myositis patients. These autoantibodies
are closely associated with a characteristic clinical subgroup, and therefore help in establishing the correct diagnosis,
classifying the myositis patients in a homogeneous subset, and facilitating the clinical and treatment follow-up. Autoantibodies
to six of the aminoacyl tRNA synthetases are each associated with a similar syndrome marked by myositis, interstitial lung
disease, arthritis, and other features constituting an "antisynthetase syndrome." Antibodies to other cytoplasmic antigens
that are involved in protein synthesis or translation factors are seen in a small proportion of patients. Antisignal recognition
particles are associated with severe, refractory myositis that differs significantly from antisynthetase syndrome. Antibodies
to the nuclear antigen are specifically seen in patietnts with DM. Several autoantibodies, including anti-U1 RNP, anti-U2
RNP, anti-Ku, and anti-PM-Scl, have been associated with scleroderma–PM overlap. In recent years, these MSAs and their antigens
have been characterized using molecular biology approaches. It is not known if the MSAs are involved in tissue injury or the
pathogenesis of PM/DM. However, an understanding of the production mechanisms of these autoantibodies can provide insight
into the etiology of this disorder. 相似文献
7.
《Modern rheumatology / the Japan Rheumatism Association》2013,23(4):199-206
AbstractEvidence of the involvement of systemic autoimmunity has been observed in polymyositis/dermatomyositis (PM/DM). Autoantibodies directed against various cellular constituents have been detected in most patients with PM/DM, and about one-third of patients have autoantibodies (myositis-specific antibodies: MSAs) that are found specifically in myositis patients. These autoantibodies are closely associated with a characteristic clinical subgroup, and therefore help in establishing the correct diagnosis, classifying the myositis patients in a homogeneous subset, and facilitating the clinical and treatment follow-up. Autoantibodies to six of the aminoacyl tRNA synthetases are each associated with a similar syndrome marked by myositis, interstitial lung disease, arthritis, and other features constituting an "antisynthetase syndrome." Antibodies to other cytoplasmic antigens that are involved in protein synthesis or translation factors are seen in a small proportion of patients. Antisignal recognition particles are associated with severe, refractory myositis that differs significantly from antisynthetase syndrome. Antibodies to the nuclear antigen are specifically seen in patietnts with DM. Several autoantibodies, including anti-U1 RNP, anti-U2 RNP, anti-Ku, and anti-PM-Scl, have been associated with scleroderma–PM overlap. In recent years, these MSAs and their antigens have been characterized using molecular biology approaches. It is not known if the MSAs are involved in tissue injury or the pathogenesis of PM/DM. However, an understanding of the production mechanisms of these autoantibodies can provide insight into the etiology of this disorder. 相似文献
8.
We aimed to study the prevalence and clinical associations of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) in a large cohort of Indian patients with idiopathic inflammatory myositis (IIM). Clinical details and serum samples were collected from patients with IIM (satisfying Bohan and Peter Criteria, 1975) and CTD-associated myositis. Sera were analysed for antibodies against SRP, Mi2, Jo1, PL7, PL12, EJ, OJ, Ro52, Ku, Pm-Scl 75 and PM-Scl 100, using immunoblot assay. The cohort comprised 124 patients with IIM (M:F = 1:3.6). Fifty-five of them had dermatomyositis (DM), 22 had juvenile dermatomyositis (JDM), 25 had polymyositis (PM) and 22 had connective tissue disease-associated myositis (CTD myositis). Mean disease duration was 10.9 months. ANA was positive in 84 (68.9 %), and MSAs in 61 (49.2 %) patients. Among MSAs, autoantibodies to Mi2, synthetase (Jo1, PL7, PL12, EJ) and SRP were present in 26 (20.9 %), 29 (23.4 %) and 6 (4.8 %) patients, respectively. Prevalence of MAAs was as follows: antibodies to Ro52 in 45 (36.3 %), Ku and PM-Scl 75 in 13 (10.5 %) and PM-Scl 100 in 5 (4 %) patients. Anti-Mi2 antibodies were positively associated with DM (21/55, 38.2 %; p < 0.0001) and pharyngeal weakness (13/34, 38.2 %; p = 0.004) and negatively associated with ILD (0/28; p = 0.001). ILD and mechanics’ hands were significantly more in patients with anti-synthetase antibodies (16/28, 57 % and 14/22, 63.6 %; p < 0.0001). Four of six patients with anti-SRP antibody showed poor response to multiple drugs. Higher prevalence of anti-Mi2 is probably related to higher proportion of patients with DM. Absence of ILD in patients with anti-Mi2 antibody suggests that it may protect against ILD. In Indian population also, anti-synthetase antibodies are associated with ILD, and anti-SRP antibodies with poor response to treatment. 相似文献
9.
O'Hanlon TP Rider LG Mamyrova G Targoff IN Arnett FC Reveille JD Carrington M Gao X Oddis CV Morel PA Malley JD Malley K Shamim EA Chanock SJ Foster CB Bunch T Reed AM Love LA Miller FW 《Arthritis and rheumatism》2006,54(11):3670-3681
OBJECTIVE: To investigate possible associations of HLA polymorphisms with idiopathic inflammatory myopathy (IIM) in African Americans, and to compare this with HLA associations in European American IIM patients with IIM. METHODS: Molecular genetic analyses of HLA-A, B, Cw, DRB1, and DQA1 polymorphisms were performed in a large population of African American patients with IIM (n = 262) in whom the major clinical and autoantibody subgroups were represented. These data were compared with similar information previously obtained from European American patients with IIM (n = 571). RESULTS: In contrast to European American patients with IIM, African American patients with IIM, in particular those with polymyositis, had no strong disease associations with HLA alleles of the 8.1 ancestral haplotype; however, African Americans with dermatomyositis or with anti-Jo-1 autoantibodies shared the risk factor HLA-DRB1*0301 with European Americans. We detected novel HLA risk factors in African American patients with myositis overlap (DRB1*08) and in African American patients producing anti-signal recognition particle (DQA1*0102) and anti-Mi-2 autoantibodies (DRB1*0302). DRB1*0302 and the European American-, anti-Mi-2-associated risk factor DRB1*0701 were found to share a 4-amino-acid sequence motif, which was predicted by comparative homology analyses to have identical 3-dimensional orientations within the peptide-binding groove. CONCLUSION: These data demonstrate that North American IIM patients from different ethnic groups have both shared and distinct immunogenetic susceptibility factors, depending on the clinical phenotype. These findings, obtained from the largest cohort of North American minority patients with IIM studied to date, add additional support to the hypothesis that the myositis syndromes comprise multiple, distinct disease entities, perhaps arising from divergent pathogenic mechanisms and/or different gene-environment interactions. 相似文献
10.
Idiopathic inflammatory myopathies: epidemiology,classification, and diagnostic criteria 总被引:3,自引:0,他引:3
Epidemiologic studies have helped to define the prevalence and incidence of PM, DM, and IBM and have highlighted differences in risk between men and women and in the age at onset for the different forms of myositis. Additionally, these studies have shown that there is a substantially higher risk of PM and DM in certain racial groups which is likely to be genetically determined. These differences are all likely to be fundamental in terms of the pathogenesis of these diseases but, as yet, their full significance remains uncertain. They do, however, suggest that the interplay between genetic and environmental initiating factors is different in the three disorders. Additional population-based studies in homogeneous racial groups, in parallel with studies of susceptibility genes for autoimmune disease, such as those encoding the MHC and inflammatory cytokines, are needed to throw further light on the role of genetic factors in the pathogenesis of the IIMs [47]. Because of the paucity of epidemiologic data on IBM, further studies are required to determine the degree of variation in prevalence in different populations and racial groups, as well as the consistency of the male association and age spectrum of manifestations of the disease. The particularly strong association with DR3 in this form of IIM [48] clearly points to the importance of genetic factors in pathogenesis, but further studies of DR3-associated genes in the MHC and of other candidate genes are needed to define more precisely the genes that convey susceptibility to the disease in different racial groups. Epidemiologic studies also have the potential to identify environmental factors that may play a part in disease initiation in genetically susceptible individuals. Seasonal patterns of disease onset have been reported, particularly in patients with DM [49-51] as well as seasonal variation in the frequency of relapses [52], pointing to the probable involvement of intercurrent infections, ultraviolet light exposure, or other environmental factors in disease initiation and reactivation. Further prospective studies are required to determine the contribution of environmental exposures and how they interact with genetic susceptibility factors to lead to myositis. One of the major limitations of a number of the previous epidemiologic studies is the lack of precision in the diagnostic criteria used and the classification of cases of IIM. The Bohan and Peter criteria [1] which were used in most studies after 1975, were introduced before IBM was recognized as an entity distinct from PM; most of the published incidence and prevalence figures for PM are therefore likely to be inaccurate. Multicentered, interdisciplinary, prospective studies, incorporating comprehensive clinical, laboratory, and pathologic information, are needed to develop and validate better diagnostic and classification criteria and to determine the true prevalence and incidence of the many forms of IIM. 相似文献
11.
O'Hanlon TP Carrick DM Targoff IN Arnett FC Reveille JD Carrington M Gao X Oddis CV Morel PA Malley JD Malley K Shamim EA Rider LG Chanock SJ Foster CB Bunch T Blackshear PJ Plotz PH Love LA Miller FW 《Medicine》2006,85(2):111-127
The idiopathic inflammatory myopathies (IIM) are systemic connective tissue diseases defined by chronic muscle inflammation and weakness associated with autoimmunity. We have performed low to high resolution molecular typing to assess the genetic variability of major histocompatibility complex loci (HLA-A, -B, -Cw, -DRB1, and -DQA1) in a large population of European American patients with IIM (n = 571) representing the major myositis autoantibody groups. We established that alleles of the 8.1 ancestral haplotype (8.1 AH) are important risk factors for the development of IIM in patients producing anti-synthetase/anti-Jo-1, -La, -PM/Scl, and -Ro autoantibodies. Moreover, a random forests classification analysis suggested that 8.1 AH-associated alleles B*0801 and DRB1*0301 are the principal HLA risk markers. In addition, we have identified several novel HLA susceptibility factors associated distinctively with particular myositis-specific (MSA) and myositis-associated autoantibody (MAA) groups of the IIM. IIM patients with anti-PL-7 (anti-threonyl-tRNA synthetase) autoantibodies have a unique HLA Class I risk allele, Cw*0304 (pcorr = 0.046), and lack the 8.1 AH markers associated with other anti-synthetase autoantibodies (for example, anti-Jo-1 and anti-PL-12). In addition, HLA-B*5001 and DQA1*0104 are novel potential risk factors among anti-signal recognition particle autoantibody-positive IIM patients (pcorr = 0.024 and p = 0.010, respectively). Among those patients with MAA, HLA DRB1*11 and DQA1*06 alleles were identified as risk factors for myositis patients with anti-Ku (pcorr = 0.041) and anti-La (pcorr = 0.023) autoantibodies, respectively. Amino acid sequence analysis of the HLA DRB1 third hypervariable region identified a consensus motif, 70D (hydrophilic)/71R (basic)/74A (hydrophobic), conferring protection among patients producing anti-synthetase/anti-Jo-1 and -PM/Scl autoantibodies. Together, these data demonstrate that HLA signatures, comprising both risk and protective alleles or motifs, distinguish IIM patients with different myositis autoantibodies and may have diagnostic and pathogenic implications. Variations in associated polymorphisms for these immune response genes may reflect divergent pathogenic mechanisms and/or responses to unique environmental triggers in different groups of subjects resulting in the heterogeneous syndromes of the IIM. 相似文献
12.
Anna Ghirardello Nicola Bassi Lavinia Palma Elisabetta Borella Marta Domeneghetti Leonardo Punzi Andrea Doria 《Current rheumatology reports》2013,15(6):1-10
Inflammatory myopathies are a group of acquired diseases, characterized by immunoflogistic processes primarily involving the skeletal muscle. According to recent classification criteria, four major diseases have been identified: polymyositis (PM), dermatomyositis (DM), sporadic inclusion body myositis (IBM), and necrotizing autoimmune myositis (NAM). Autoantibodies can be found in the sera of most patients with myositis. Myositis-specific autoantibodies (MSAs) are markers of very specific disease entities within the spectrum of myositis, and target proteins involved in key processes of protein synthesis. Myositis autoantigens comprise the well-defined aminoacyl-tRNA synthetases, the Mi-2 helicase/histone deacetylase protein complex, and the signal recognition particle (SRP) ribonucleoprotein, together with novel targets such as TIF1-γ, MDA5, NXP2, SAE, and HMGCR. Recent studies suggest that autoantigens drive a B cell antigen-specific immune response in muscles. Interestingly, an increased expression of Jo-1 and Mi-2 in regenerating fibers in muscle biopsies from PM and DM patients compared to normal was demonstrated. Myositis autoantigen up-regulation was observed in neoplastic tissues, thus representing a potential link between cancer and autoimmunity in myositis. Non-immunological mechanisms seem to participate to the pathogenesis of inflammatory myopathies; induction of endoplasmic reticulum stress response in response to abnormal muscle regeneration and inflammation has recently been reported in patients with myositis. This review article provides an update of new emerging insights about the clinical and pathophysiologic role of principal autoantibodies in myositis. 相似文献
13.
Have recent immunogenetic investigations increased our understanding of disease mechanisms in the idiopathic inflammatory myopathies? 总被引:2,自引:0,他引:2
PURPOSE OF REVIEW: The idiopathic inflammatory myopathies (IIM) continue to provide a challenge given the variable effectiveness of the available treatments, and immunogenetic studies are ongoing to further elucidate IIM disease mechanisms. This review examines how recent research has improved our understanding of the mechanisms that lead to IIM. RECENT FINDINGS: HLA-DRB1 studies in a large homogenous cohort of UK Caucasian patients have confirmed that polymyositis (PM) and dermatomyositis (DM) are not genetically identical diseases while other studies have shown that tumor necrosis factor alpha is genetically implicated in disease susceptibility. Some remarkable results from an international collaboration, correlating gene-environment interactions, clearly suggest that ultraviolet light is capable of modulating both clinical and immunologic features of IIMs. Studies on microchimerism are unraveling interesting associations in juvenile DM patients, and bolstering the hypothesis that myositis may be an 'allo-immune' disease. mRNA gene expression profiling is helping to increase our understanding of myositis pathogenesis, whilst animal models have provided new information on the roles of Th1 responses and nitric oxide synthase in muscle disease. New candidate genes have been examined in inclusion body myositis (IBM), and a novel gene transfer experiment has been conducted, which led to significant changes in expression of the IBM phenotype. SUMMARY: Improving the understanding of the immunogenetics and immunopathogenesis of the IIMs may in the future provide novel therapeutic targets, and thus improve outcomes in these difficult diseases. 相似文献
14.
Shamim EA Rider LG Pandey JP O'Hanlon TP Jara LJ Samayoa EA Burgos-Vargas R Vazquez-Mellado J Alcocer-Varela J Salazar-Paramo M Kutzbach AG Malley JD Targoff IN Garcia-De la Torre I Miller FW 《Arthritis and rheumatism》2002,46(7):1885-1893
OBJECTIVE: As part of a larger, worldwide study of the ethnogeography of myositis, we evaluated the clinical, serologic, and immunogenetic features of Mestizo (Mexican and Guatemalan) and North American Caucasian patients with idiopathic inflammatory myopathy (IIM). METHODS: Clinical manifestations, autoantibodies, HLA-DRB1 and DQA1 alleles, and immunoglobulin Gm/Km allotypes were compared between 138 Mestizos with IIM and 287 Caucasians with IIM, using the same classification criteria and standardized questionnaires. RESULTS: IIM in Mestizo patients was characterized by a higher proportion of dermatomyositis (69% of adult Mestizos versus 35% of adult Caucasians; P < 0.001) and anti-Mi-2 autoantibodies (30% versus 7% of adults, respectively, and 32% versus 4% of children, respectively; P < 0.01). Genetic risk factors also differed in these populations. Whereas Mestizos had no HLA risk factors for IIM, HLA-DRB1*0301, the linked allele DQA1*0501, and DRB1 alleles sharing the first hypervariable region motif (9)EYSTS(13) were major risk factors in Caucasian patients with IIM. Furthermore, different HLA-DRB1 and DQA1 alleles were associated with anti-Mi-2 autoantibodies (DRB1*04 and DQA1*03 in Mestizos and DRB1*07 and DQA1*02 in Caucasians). Immunoglobulin gamma-chain allotypes Gm(1), Gm(17) (odds ratio for both 11.3, P = 0.008), and Gm(21) (odds ratio 7.3, P = 0.005) and kappa-chain allotype Km(3) (odds ratio 7.3, P = 0.005) were risk factors for IIM in Mestizos; however, no Gm or Km allotypes were risk or protective factors in Caucasians. In addition, Gm and Km phenotypes were unique risk factors (Gm 1,3,17 5,13,21 and Gm 1,17 23 21 and Km 3,3) or protective factors (Km 1,1) for the development of myositis and anti-Mi-2 autoantibodies (Gm 1,2,3,17 23 5,13,21) in adult Mestizos. CONCLUSION: IIM in Mesoamerican Mestizos differs from IIM in North American Caucasians in the frequency of phenotypic features and in the immune-response genes predisposing to and protecting from myositis and anti-Mi-2 autoantibodies at 4 chromosomal loci. These and other data suggest the likelihood that the expression of IIM is modulated by different genes and environmental exposures around the world. 相似文献
15.
Immunogenetic features in 120 Japanese patients with idiopathic inflammatory myopathy 总被引:3,自引:0,他引:3
Furuya T Hakoda M Tsuchiya N Kotake S Ichikawa N Nanke Y Nakajima A Takeuchi M Nishinarita M Kondo H Kawasaki A Kobayashi S Mimori T Tokunaga K Kamatani N 《The Journal of rheumatology》2004,31(9):1768-1774
OBJECTIVE: To examine the role of HLA-DRB1 and tumor necrosis factor (TNF) promoter genotypes in the development and the autoantibody profiles of idiopathic inflammatory myopathy (IIM) in Japanese patients. METHODS: HLA-DRB1 and TNF promoter genotypes were determined, and serum antinuclear autoantibodies were identified in 120 adult Japanese patients with IIM [72 with dermatomyositis (DM), 30 with polymyositis (PM), 18 with myositis overlapping with other collagen vascular diseases], as well as in 265 controls. RESULTS: Forty-two patients (35%) were positive for myositis-specific autoantibodies (MSA), including 37 (31%) for anti-aminoacyl-tRNA synthetase (ARS) autoantibodies. Allele carrier frequency of HLA-DRB1*0803 was increased in the patients with IIM [p = 0.02, corrected p (pc) NS, 23% vs 14%, odds ratio (OR) = 1.9 (95% confidence interval, CI = 1.1-3.2)], with PM [p = 0.006, pc NS, 33%, OR 3.1 (95% CI 1.3-7.1)], and with anti-ARS autoantibodies [27%, p = 0.04, OR 2.3 (95% CI 1.0-5.1)] compared with controls. DRB1*0405 was increased in patients with anti-ARS autoantibodies compared with controls [41% vs 25%, p = 0.04, pc NS, OR 2.1 (95% CI 1.0-4.3)]. TNF promoter genotype was associated with the presence of interstitial lung disease (ILD). The carriage of a TNF-a haplotype formed by -1031C, -863A, and -857C was increased in the patients with ILD versus those without ILD [33% vs 18%, p = 0.05, pc NS, OR 2.3 (95% CI 0.94-5.5)]. CONCLUSION: HLA-DRB1 alleles were associated with development of IIM and MSA in a Japanese population. 相似文献
16.
Ju Ann TAN Peter J. ROBERTS‐THOMSON Peter BLUMBERGS Paul HAKENDORF Sally R. COX Vidya LIMAYE 《International journal of rheumatic diseases》2013,16(3):331-338
Aim: To describe the epidemiology of biopsy‐proven idiopathic inflammatory myopathies (IIM) in South Australia (SA). Methods: Cases of IIM were ascertained by review of all muscle biopsy reports from the Neuropathology Laboratory, Hanson Institute (wherein all adult muscle biopsies in SA are reported) from 1980 to 2009. Clinical correlation of these patients by review of medical records was undertaken. SA population denominator numbers were obtained from the Australian Bureau of Statistics. Results: Three hundred and fifty‐two biopsy‐proven cases of IIM were identified between 1980 and 2009. The overall annual incidence of IIM appeared to be rising with a mean incidence of eight cases per million population (95% CI: 7.2–8.9). This corresponded with an increasing annual incidence of inclusion body myositis (IBM) (prevalence of 50.5 cases per million population in 2009, 95% CI: 40.2–62.7). A female preponderance was noted in both dermatomyositis (DM) (F : M = 2.75 : 1.00) and polymyositis (PM) (F : M = 1.55 : 1.00) but gender distribution was almost equal in IBM (F : M = 1.1 : 1.0). Mean age at diagnosis for IBM (67.5 years) was higher than for DM (55.1 years) and PM (59.0 years). A higher proportion of DM patients reported living in urban dwellings and DM patients tended to be predominantly professionals. Conclusions: In SA there is an increasing incidence of IBM and the prevalence is one of the highest reported to date. This may reflect an increase in the number of biopsies performed, improved histological techniques or a genuine increase in incidence. 相似文献
17.
《Best Practice & Research: Clinical Rheumatology》2020,34(1):101484
Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of inflammatory myopathies whose common feature is immune-mediated muscle injury. There are distinct subgroups including dermatomyositis (DM), polymyositis (PM), inclusion body myositis, and immune-mediated necrotizing myopathy. Antisynthetase syndrome is also emerging as a distinct subgroup with its unique muscle histopathological characteristic of perifascicular necrosis. While the newly updated EULAR/ACR Classification Criteria for IIM have brought advancements in diagnosis and the exclusion of mimickers, the use of only one autoantibody in the derivation of the schema limits its use. Similarly, while the advent of multiple novel therapeutics in the treatment of myositis has been exciting, it has also highlighted the scarcity of validated outcome measures. The purpose of our review is to highlight the updated classification criteria of myositis, newly reported clinical phenotypes associated with myositis autoantibodies, the measurement of outcomes, and emerging treatments in the field. 相似文献
18.
Takahisa Gono Yasushi Kawaguchi Tomoko Sugiura Takefumi Furuya Manabu Kawamoto Masanori Hanaoka Hisashi Yamanaka 《Modern rheumatology / the Japan Rheumatism Association》2010,20(5):466-470
The aim of the present study was to evaluate whether the interferon-induced helicase (IFIH1) Ala946Thr (rs1990760 A>G) polymorphism is associated with susceptibility to systemic lupus erythematosus (SLE) and dermatomyositis
(DM) or polymyositis (PM) in the Japanese population. The study population consisted of 243 SLE patients, 125 DM/PM patients,
and 268 healthy controls from Japan. A Taqman single nucleotide polymorphism genotyping assay was designed for rs1990760 by
Applied Biosystems. There were no significant differences between SLE and DM/PM patients and healthy controls regarding the
frequency of each genotype and allele. However, the frequency of the AA genotype and the A allele tended to be higher in PM
patients with interstitial lung disease (ILD). Additionally, when comparing the AA and AG + GG genotypes at rs1990760, the
AA genotype was significantly more frequent in PM patients with ILD than in healthy controls [odds ratio, 3.23 (95% confidence
interval, 1.06–9.81); P = 0.04] or in PM patients without ILD [odds ratio, 5.40 (95% confidence interval, 1.37–21.26); P = 0.027]. Our observations suggest that the G allele protects against the onset of ILD and that the AA genotype is a risk
factor for lung injury in PM patients. 相似文献
19.
IDIOPATHIC INFLAMMATORY MYOPATHY: CLINICOPATHOLOGICAL OBSERVATIONS IN THE INDIAN POPULATION 总被引:1,自引:0,他引:1
PRASAD M. L.; SARKAR C.; ROY S.; BAGCHI U.; SINGH R. R.; SINGH Y. N.; SHARMA S.; MALAVIYA A. N. 《Rheumatology (Oxford, England)》1992,31(12):835-839
The present study attempts to investigate the pathological basisof the two clinically different forms of idiopathic inflammatorymyopathy (IIM) namely, polymyositis (PM) and dermatomyositis(DM). Clinicopathological analysis of 73 cases showed that musclefibre necrosis and regeneration were more frequent in PM thanin DM, the latter being significantly so (P<0.05). On theother hand, vasculitis was more often associated with DM whileperifascicular atrophy of the muscle fibres was confined toit. Vasculitis was present in eight cases. Its incidence inpatients with myositis with systemic connective tissue disease(4/9) was significantly more than in other PM and DM patients(P<0.01). An equally significant higher frequency of perimysialinflammatory infiltrate was also seen in the former as comparedto the latter. Interestingly, idiopathic DM affected men asoften as women and juvenile IIM affected boys more frequentlythan girls. A female predilection was noted in the remaininggroups of IIM. These observations indicate that there may besome basic immunopathogenetic differences between polymyositisand dermatomyositis as well as between idiopathic PM<DM andthat associated with systemic connective tissue diseases. Thoughthe number of patients studied is small, the absence of femalepredilection in idiopathic DM and juvenile IIM may be peculiarto the IIM in the tropics. KEY WORDS: Dermatomyositis, Myositis, Polymyositis
Present address: Department of Pathology, G. B. Pant Hospital,New Delhi, India.
Present address: Department of Immunology, Sanjay Gandhi Post-GraduateInstitute of Medical Sciences, Lucknow, India.
|Present address: Hunter Immunology Unit, Royal Newcastle Hospital,Newcastle, New South Wales, Australia.
¶Present address: Department of Pathology, Rush PresbyterianHospital, Chicago, Illinois. 相似文献
20.
Yoshioki Yamasaki Hidehiro Yamada Toshiko Nozaki Jun Akaogi Cody Nichols Robert Lyons Anthony Chin Loy Edward K. L. Chan Westley H. Reeves Minoru Satoh 《Arthritis \u0026amp; Rheumatology》2006,54(6):2004-2009