Myositis Autoantibodies Research Articles

Brief Report: Ultraviolet Radiation Exposure Is Associated With Clinical and Autoantibody Phenotypes in Juvenile Myositis

Genetic and environmental factors may contribute to the etiology of the juvenile idiopathic inflammatory myopathies (IIMs), which are systemic autoimmune diseases that are characterized by muscle and skin inflammation. We undertook this study to investigate the association between ultraviolet radiation (UVR) exposure and the clinical and autoantibody expression of juvenile IIM. The relationship between UVR exposure in the month before symptom onset and the prevalence of juvenile dermatomyositis (DM), compared to juvenile polymyositis (PM), was assessed in 298 juvenile IIM patients. Among the patients with juvenile DM, the association between UVR exposure and presence of myositis autoantibodies was assessed. Regression models were stratified by sex and race. The association between the regional UV index in US geoclimatic zones and the clinical and autoantibody subgroups was examined by weighted least squares regression analysis. Among girls in this population, the odds of having juvenile DM, compared to juvenile PM, increased per unit increase in the patients' highest UV index in the month before symptom onset (odds ratio [OR] 1.18, 95% confidence interval 1.00-1.40). Moreover, both the mean and highest UV indices were associated with increasing odds of having anti-p155/140 autoantibodies, with the strongest odds in white males (ORs of 1.30 and 1.23, respectively). No association was observed between the UV index and presence of anti-MJ autoantibodies or lack of any myositis autoantibodies. Across all 9 US geoclimatic regions, the mean UV index was associated with increasing odds of having juvenile DM and anti-p155/140 autoantibodies, but decreasing odds of having anti-MJ autoantibodies. Short-term UVR exposure prior to illness onset may have a role in the clinical and serologic expression of juvenile myositis. Further research examining the mechanisms of action of UVR in the pathogenesis of juvenile IIM is suggested from these findings.

SAT0031 Anti-RO52 autoantibody epitope mapping in european cohort of myositis patients

BackgroundThe most frequent myositis associated autoautoantibodies are directed to Ro52-kd protein (12-26%). Antibodies to the immunodominant epitope (p200) of Ro52 are associated with SLE and Sjögren’s syndrome (SjS) with suggestion...

AB0493 Association between antiviral igm antibodies and myositis autoantibodies in patients with autoimmune myositis in bulgarian population

BackgroundConsiderable evidences indicate that the viruses may be important environmental factors in the pathogenesis of the connective tissue diseases – systemic lupus erythematodes, systemic sclerosis, myositis, etc.1 Viruses activate a...

Autoantibodies in Polymyositis and Dermatomyositis

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.

The Clinical Phenotypes of the Juvenile Idiopathic Inflammatory Myopathies

The juvenile idiopathic inflammatory myopathies (JIIM) are systemic autoimmune diseases characterized by skeletal muscle weakness, characteristic rashes, and other systemic features. Although juvenile dermatomyositis (JDM), the most common form of JIIM, has been well studied, the other major clinical subgroups of JIIM, including juvenile polymyositis (JPM) and juvenile myositis overlapping with another autoimmune or connective tissue disease (JCTM), have not been well characterized, and their similarity to the adult clinical subgroups is unknown. We enrolled 436 patients with JIIM, including 354 classified as JDM, 33 as JPM, and 49 as JCTM, in a nationwide registry study. The aim of the study was to compare demographics; clinical features; laboratory measures, including myositis autoantibodies; and outcomes among these clinical subgroups, as well as with published data on adult patients with idiopathic inflammatory myopathies (IIM) enrolled in a separate natural history study.We used random forest classification and logistic regression modeling to compare clinical subgroups, following univariate analysis. JDM was characterized by typical rashes, including Gottron papules, heliotrope rash, malar rash, periungual capillary changes, and other photosensitive and vasculopathic skin rashes. JPM was characterized by more severe weakness, higher creatine kinase levels, falling episodes, and more frequent cardiac disease. JCTM had more frequent interstitial lung disease, Raynaud phenomenon, arthralgia, and malar rash. Differences in autoantibody frequency were also evident, with anti-p155/140, anti-MJ, and anti-Mi-2 seen more frequently in patients with JDM, anti-signal recognition particle and anti-Jo-1 in JPM, and anti-U1-RNP, PM-Scl, and other myositis-associated autoantibodies more commonly present in JCTM. Mortality was highest in patients with JCTM, whereas hospitalizations and wheelchair use were highest in JPM patients. Several demographic and clinical features were shared between juvenile and adult IIM subgroups. However, JDM and JPM patients had a lower frequency of interstitial lung disease, Raynaud phenomenon, “mechanic’s hands” and carpal tunnel syndrome, and lower mortality than their adult counterparts. We conclude that juvenile myositis is a heterogeneous group of illnesses with distinct clinical subgroups, defined by varying clinical and demographic characteristics, laboratory features, and outcomes.

Quoi de neuf en médecine interne ?

This paper summarizes a review of the medical literature focused on the field of internal medicine and dermatology, particularly cutaneous lupus erythematosus, dermatomyositis, cutaneous sarcoidosis, systemic sclerosis and cutaneous scleroderma, from September 2011 to October 2012. Our objective was to select the main articles that bring new information and significant advances useful for the dermatologist and internist in their daily practice and for the pathophysiological understanding of these affections. Thus, recent advances in the field of the following diseases were selected: cutaneous lupus erythematosus, sarcoidosis and systemic sclerosis treatments, neutrophilic dermatosis associated with lupus erythematosus, NETosis mechanism and myositis autoantibodies associated with dermatomyositis.

Novel autoantibodies and clinical phenotypes in adult and juvenile myositis

Autoantibodies targeting intracellular proteins involved in key processes are detected in patients with idiopathic inflammatory myopathies. These myositisspecific autoantibodies have been increasingly demonstrated to correlate with distinct clinical phenotypes within the myositis spectrum. This review highlights the clinical associations of the myositisspecific autoantibodies, with particular attention to the recently identified and characterized novel myositis autoantibodies: p155/140, p140 (MJ), CADM-140 (MDA5), SAE, and 200/100.

Myositis autoantibodies in Korean patients with inflammatory myositis: Anti-140-kDa polypeptide antibody is primarily associated with rapidly progressive interstitial lung disease independent of clinically amyopathic dermatomyositis

BackgroundTo investigate the association between myositis autoantibodies and clinical subsets of inflammatory myositis in Korean patients.MethodsImmunoprecipitation was performed using the sera of classic polymyositis (PM) (n = 11) and dermatomyositis (DM) (n = 38) patients who met the Bohan and Peter criteria for definite inflammatory myositis. A panel of defined myositis autoantibodies was surveyed to investigate the association between each autoantibody and clinical subsets of inflammatory myositis.ResultsEither MSAs, anti-p140, or anti-p155/140 antibodies were found in 63.3% (31/49) of the study subjects. Anti-140-kDa-polypeptide (anti-p140) (18.4%, 9/49) and anti-155/140-kDa polypeptide (anti-p155/140) (16.3%, 8/49) antibodies were the most common, followed by anti-Mi2 (14.3%, 7/49), anti-ARS (12.2%, 6/49) and anti-SRP (2.0%, 1/49) antibodies. All MSAs and anti-p140 and anti-p155/140 antibodies were mutually exclusive. Anti-p140 (23.7%, 9/38), anti-p155/140 (21.1%, 8/38), and anti-Mi2 (18.4%, 3/38) antibodies were found exclusively in DM patients. Anti-p140 antibody was associated with rapidly progressive interstitial lung disease (ILD) (p = 0.001), with a sensitivity of 100.0% (4/4) and a specificity of 85.3% (29/34) in DM patients. Anti-p155/140 antibody was associated with cancer-associated DM (p = 0.009), with a sensitivity of 55.6% (5/9) and a specificity of 89.7% (26/29). Cancer-associated survival was significantly worse when anti-p155/140 antibody was present (19.2 ± 7.6 vs. 65.0 ± 3.5 months, p = 0.032). Finally, anti-ARS antibodies were associated with stable or slowly progressive ILD in PM and DM patients (p = 0.005).ConclusionsAnti-p140 and anti-p155/140 antibodies were commonly found autoantibodies in Korean patients with inflammatory myositis. Despite the lack of clinically amyopathic DM patients in the study subjects, a strong association was observed between anti-p140 antibody and rapidly progressive ILD. Anti-p155/140 antibody was associated with cancer-associated myositis and poor survival.

Environmental factors preceding illness onset differ in phenotypes of the juvenile idiopathic inflammatory myopathies

Objective. To assess whether certain environmental factors temporally associated with the onset of juvenile idiopathic inflammatory myopathies (JIIMs) differ between phenotypes. Methods. Physicians completed questionnaires regarding documented infections, medications, immunizations and an open-ended question about other noted exposures within 6 months before illness onset for 285 patients with probable or definite JIIM. Medical records were reviewed for 81% of the patients. Phenotypes were defined by standard clinical and laboratory measures. Results. Sixty per cent of JIIM patients had a reported exposure within 6 months before illness onset. Most patients (62%) had one recorded exposure, 26% had two and 12% had three to five exposures. Patients older than the median age at diagnosis, those with a longer delay to diagnosis and those with anti-signal recognition particle autoantibodies had a higher frequency of documented exposures [odds ratios (ORs) 95% CI 3.4, 31]. Infections were the most common exposure and represented 44% of the total number of reported exposures. Non-infectious exposures included medications (18%), immunizations (11%), stressful life events (11%) and unusual sun exposure (7%). Exposures varied by age at diagnosis, race, disease course and the presence of certain myositis autoantibodies. Conclusion. The JIIMs may be related to multiple exposures and these appear to vary among phenotypes.

Cancer-Associated Myositis and Anti-p155 Autoantibody in a Series of 85 Patients With Idiopathic Inflammatory Myopathy

A new autoantibody against a 155-kDa protein has been described in patients with myositis. We conducted a study to determine the occurrence and types of cancer occurring in a cohort of patients with polymyositis (PM) or dermatomyositis (DM) and analyzed the value of this autoantibody as a serologic marker of cancer-associated myositis (CAM). Serum samples from all patients were examined by protein immunoprecipitation assays with HeLa cells to determine the presence of a 155-kDa protein band. HLA-DRB1 and DQA1 typing was performed by polymerase chain reaction-reverse sequence specific oligonucleotide. Statistical analyses were carried out with the Mann Whitney U and Fisher exact tests. Associations were determined using odds ratios (ORs) with 95% confidence intervals (CI). Eighty-five patients with myositis (20 PM and 65 DM) were included. CAM was detected in 16 patients (19%), 14 with DM. The shawl sign rash was significantly more frequent in patients with CAM than in those without (p < 0.01). Adenocarcinoma was the most frequent type of cancer (87.5%). Anti-p155 autoantibody was found in 1 of the 20 (5%) patients with PM and in 15 of the 65 (23%) patients with DM. A relationship between anti-p155 and CAM was found in DM patients (OR, 23; 95% CI, 5.23-101.2). The HLA-DQA1*0102 allele was not found in any of the anti-p155-positive patients. The prevalence of CAM in our cohort was 19%. Autoantibody against p155 was highly related to CAM and could be a reliable marker of cancer in patients with DM.

Cancer-associated myositis and anti-p155 autoantibody in a series of 85 patients with idiopathic inflammatory myopathy

Cancer-associated myositis and anti-p155 autoantibody in a series of 85 patients with idiopathic inflammatory myopathy

Ultraviolet radiation intensity predicts the relative distribution of dermatomyositis and anti–Mi‐2 autoantibodies in women

Because studies suggest that ultraviolet (UV) radiation modulates the myositis phenotype and Mi-2 autoantigen expression, we conducted a retrospective investigation to determine whether UV radiation may influence the relative prevalence of dermatomyositis and anti-Mi-2 autoantibodies in the US. We assessed the relationship between surface UV radiation intensity in the state of residence at the time of onset with the relative prevalence of dermatomyositis and myositis autoantibodies in 380 patients with myositis from referral centers in the US. Myositis autoantibodies were detected by validated immunoprecipitation assays. Surface UV radiation intensity was estimated from UV Index data collected by the US National Weather Service. UV radiation intensity was associated with the relative proportion of patients with dermatomyositis (odds ratio [OR] 2.3, 95% confidence interval [95% CI] 0.9-5.8) and with the proportion of patients expressing anti-Mi-2 autoantibodies (OR 6.0, 95% CI 1.1-34.1). Modeling of these data showed that these associations were confined to women (OR 3.8, 95% CI 1.3-11.0 and OR 17.3, 95% CI 1.8-162.4, respectively) and suggests that sex influences the effects of UV radiation on autoimmune disorders. Significant associations were not observed in men, nor were UV radiation levels related to the presence of antisynthetase or anti-signal recognition particle autoantibodies. This first study of the distribution of myositis phenotypes and UV radiation exposure in the US showed that UV radiation may modulate the clinical and immunologic expression of autoimmune disease in women. Further investigation of the mechanisms by which these effects are produced may provide insights into pathogenesis and suggest therapeutic or preventative strategies.

Ethnic Influence on Disease Manifestations and Autoantibodies in Chinese-Descent Patients with Systemic Sclerosis

To investigate ethnic influence on disease manifestations and autoantibody profile in patients of Chinese descent with systemic sclerosis (SSc). In a retrospective study of a multiethnic SSc cohort followed over a 17-year period, disease manifestations and autoantibody profile of patients of European and Chinese descent were compared. There were 300 patients of European descent and 36 of Chinese descent, with similar proportions of women (81% and 72%, respectively) and patients with diffuse SSc (50% and 56%). Patients of Chinese descent [mean age+/-standard deviation (SD) 52+/-16 yrs; p=0.05] were diagnosed at an older age compared to patients of European descent (mean+/-SD 46+/-12 yrs). Patients of Chinese descent compared to those of European descent had less frequent joint (69% vs 86%; p=0.01) and gastrointestinal involvement (78% vs 94%; p=0.004), but increased prevalence of myositis (17% vs 5%; p=0.01). Patients of Chinese descent had less frequent digital ulceration (36% vs 55%; p=0.04), and an absence of renal crisis. The frequency of cardiac and pulmonary involvement was similar in both groups. More patients of Chinese than of European descent were positive for anti-topoisomerase-I (47% vs 27%; p=0.02), anti-Ro (36% vs 10%; p=0.001), and anti-U1RNP (17% vs 5%; p=0.03) antibodies. The observed differences for anti-topoisomerase-I, anti-Ro, and joint and gastrointestinal manifestations persisted in the subgroup analysis of patients matched for sex, disease subtype, and age at diagnosis. Patients of Chinese descent have milder SSc disease with less frequent joint and gastrointestinal manifestations, less severe vasculopathy, but increased prevalence of myositis and certain autoantibodies. Research is needed to identify determinants (genetic, environmental, and cultural factors) of the relationship between ethnicity and disease.

Autoantibodies and their significance in myositis

Myositis autoantibodies continue to be the subject of substantial interest, with several significant recent developments. Recent studies have emphasized that anti-Jo-1 or other antisynthetases can be associated with interstitial lung disease, even in the absence of myositis. Anti-Jo-1 autoantibody levels were shown to correlate with disease activity over time. Immunization of mice with anti-Jo-1 led to muscle and lung inflammation, reminiscent of human disease. The complexity of the antibody picture in myositis continues to increase. Several new autoantibodies have been described or better characterized. Among these were a new antisynthetase reactive with phenylalanyl-transfer RNA synthetase (anti-Zo); an autoantibody that immunoprecipitates 155- and 140-kD proteins and was common in children but seemed to be associated with malignancy in adults; and an autoantibody to a small ubiquitin-like modifier--activating enzyme associated with dermatomyositis and interstitial lung disease. These findings have significant clinical implications and suggest promising areas of further research.

The diagnostic utility of myositis autoantibody testing for predicting the risk of cancer-associated myositis

Objectives:There is a known association between myositis and cancer. The risk is greater in dermatomyositis (DM) than polymyositis (PM), although reliable methods to predict cancer risk in specific patients with...

Autoantibodies in Canine Masticatory Muscle Myositis Recognize a Novel Myosin Binding Protein-C Family Member

Inflammatory myopathies are a group of autoimmune diseases that affect muscles. In humans, the most common inflammatory myopathies are polymyositis, dermatomyositis, and inclusion body myositis. Autoantibodies may be found in humans with inflammatory myopathies, and these play an important role in diagnosis and disease classification. However, these Abs are typically not muscle specific. Spontaneously occurring canine inflammatory myopathies may be good parallel disorders and provide insights into human myositis. In dogs with inflammatory myopathy, muscle-specific autoantibodies have been found, especially in masticatory muscle myositis. We have identified the major Ag recognized by the autoantibodies in canine masticatory muscle myositis. This Ag is a novel member of the myosin binding protein-C family, which we call masticatory myosin binding protein-C (mMyBP-C). mMyBP-C is localized not only within the masticatory muscle fibers, but also at or near their cell surface, perhaps making it accessible as an immunogen. The gene for mMyBP-C also exists in humans, and mMyBP-C could potentially play a role in certain human inflammatory myopathies. Understanding the role of mMyBP-C in this canine inflammatory myopathy may advance our knowledge of mechanisms of autoimmune inflammatory muscle diseases, not only in dogs, but also in humans.

Rituximab for the treatment of juvenile dermatomyositis: A report of four pediatric patients

Juvenile dermatomyositis (DM) is a chronic inflammatory myopathy of childhood primarily affecting the muscles and skin. Treatment for juvenile DM is often difficult, and conventional therapies include corticosteroids and other immune suppressants. We reviewed the records of 4 patients with juvenile DM who received the B cell-depleting anti-CD20 monoclonal antibody rituximab to determine whether this therapy resulted in improved control of their juvenile DM. This is a retrospective review of 4 pediatric patients ages 10-17 years with juvenile DM who were treated with rituximab. All patients were tested for myositis autoantibodies and received weekly rituximab infusions for a total of 4 doses. Two patients received repeat courses of rituximab 1 year after their first dose. Patients were followed up between 12 and 24 months after their first course of rituximab, and their strength, muscle enzymes, and rash were reviewed. One patient was positive for a myositis-specific antibody, anti-Mi-2, and demonstrated striking reductions in her muscle enzyme levels for 1 year after rituximab therapy. Following a second course of rituximab, this patient remained disease free for 14 months before requiring a third course of rituximab. Two myositis antibody-negative patients showed clinical improvement and tolerated lower doses of corticosteroids following treatment with rituximab. Finally, 1 patient had worsening of her disease following rituximab. These cases highlight the potential for anti-B cell therapies in the treatment of juvenile DM in both myositis-specific autoantibody-positive and -negative patients.

Heterogeneity of autoantibodies in 100 patients with autoimmune myositis: insights into clinical features and outcomes

The objective of this study was to determine the prevalence, mutual associations, clinical manifestations, and diagnoses associated with serum autoantibodies, as detected using recently available immunoassays, in patients with autoimmune myositis (AIM). Sera and clinical data were collected from 100 patients with AIM followed longitudinally. Sera were screened cross-sectionally for 21 autoantibodies by multiplex addressable laser bead immunoassay, line blot immunoassay, immunoprecipitation of in vitro translated recombinant protein, protein A assisted immunoprecipitation, and enzyme-linked immunosorbent assay. Diagnoses were determined using the Bohan and Peter classification as well as recently proposed classifications. Relationships between autoantibodies and clinical manifestations were analyzed by multiple logistic regression. One or more autoantibodies encompassing 19 specificities were present in 80% of the patients. The most common autoantibodies were anti-Ro52 (30% of patients), anti-Ku (23%), anti-synthetases (22%), anti-U1RNP (15%), and anti-fibrillarin (14%). In the presence of autoantibodies to Ku, synthetases, U1RNP, fibrillarin, PM-Scl, or scleroderma autoantigens, at least one more autoantibody was detected in the majority of sera and at least two more autoantibodies in over one-third of sera. The largest number of concurrent autoantibodies was six autoantibodies. Overall, 44 distinct combinations of autoantibodies were counted. Most autoantibodies were unrestricted to any AIM diagnostic category. Distinct clinical syndromes and therapeutic responses were associated with anti-Jo-1, anti-fibrillarin, anti-U1RNP, anti-Ro, anti-Ro52, and autoantibodies to scleroderma autoantigens. We conclude that a significant proportion of AIM patients are characterized by complex associations of autoantibodies. Certain myositis autoantibodies are markers for distinct overlap syndromes and predict therapeutic outcomes. The ultimate clinical features, disease course, and response to therapy in a given AIM patient may be linked to the particular set of associated autoantibodies. These results provide a rationale for patient profiling and its application to therapeutics, because it cannot be assumed that the B-cell response is the same even in the majority of patients in a given diagnostic category.

HLA polymorphisms in African Americans with idiopathic inflammatory myopathy: Allelic profiles distinguish patients with different clinical phenotypes and myositis autoantibodies

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. 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). 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. 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.

Idiopathic inflammatory myopathy: autoantibody update.

Several defined, specific autoantibodies have been associated with polymyositis and dermatomyositis. These include autoantibodies to at least six of the aminoacyl-transfer-ribonucleic-acid synthetases; to the signal recognition particle; to the protein complexes labeled Mi-2 and PM-Scl; and several autoantibodies, such as anti-U1nRNP and anti-Ro/SSA, that have recognized associations with other conditions. These autoantibodies are a continuing area of interest. Recent studies have involved the clinical implications of these autoantibodies, and their potential significance for etiology and pathogenesis of the disease. This report will review recent studies of myositis autoantibodies and their clinical associations, both extramuscular features, such as interstitial lung disease and aspects of the myositis itself. New myositis autoantibodies continue to emerge, which may have clinical utility. Several have been associated with dermatomyositis, including juvenile dermatomyositis, which has a low frequency of traditional myositis autoantibodies. There is also new information regarding the antigenic targets of anti-Mi-2 and anti-PM-Scl, two of the earliest recognized myositis autoantibodies. New evidence over the past few years has challenged old concepts of the relationship of autoantibodies to the pathogenesis of myositis, and has suggested potential new mechanisms for the origin of the associated autoantibodies. Despite this progress, the reason for production of the autoantibodies and their role in tissue injury remain unknown.