国际风湿病杂志（原 APLAR 风湿病学杂志）是亚太地区风湿病学协会联盟的官方期刊。该杂志接受与风湿性疾病相关的临床或实验研究的原创文章，关于结缔组织疾病和其他免疫和过敏性疾病的工作。所有论文的接受标准是研究的质量和原创性及其对我们读者的意义。除非另有说明，否则稿件将由两名匿名审稿人和编辑进行同行评审。

The International Journal of Rheumatic Diseases, formerly known as the APLAR Journal of Rheumatology, is the official journal of the Asia Pacific League of Associations for Rheumatology. This journal accepts original clinical or experimental research articles related to rheumatic diseases, including work on connective tissue diseases and other immune and allergic disorders. The acceptance criteria for all submissions are based on the quality and originality of the research and its relevance to our readers. Unless otherwise specified, all manuscripts will undergo peer review by two anonymous reviewers and the editor.

国际风湿病杂志（International Journal of Rheumatic Diseases，原 APLAR 风湿病学杂志）是亚太地区风湿病学协会联盟的官方期刊。该杂志接受与风湿性疾病相关的原创临床或实验研究文章，涵盖结缔组织疾病及其他免疫和过敏性疾病的研究。所有稿件的接受标准基于研究的质量、原创性及其对读者的意义。除非另有说明，所有稿件将由两名匿名审稿人和编辑进行同行评审。

International Journal of Rheumatic Diseases

The Oxidative Balance Score (OBS) is a systematic tool to assess the effects of diet and lifestyle in relation to oxidative stress. The association between OBS and gout has not been reported previously. We conducted a cross‐sectional study to investigate the complex association between OBS and gout in US adults.
In all, 10 492 participants were included in this study. The exposure variable was OBS, which was scored by 16 dietary and four lifestyle factors. Multivariate logistic regression, subgroup analysis, and restricted cubic spline (RCS) regression were used to analyze the association between OBS and gout.
Compared with the lowest OBS quartile group (Q1), the multivariate corrected odds ratio (OR) (95% confidence interval [C]) for the highest quartile of OBS (Q4) was 0.72 (0.52–1.00) (p= .13 for trend); furthermore, the RCS showed a negative linear relationship between OBS and gout (p‐nonlinear = .606).
In conclusion, the risk of gout is higher with high OBS. The prevalence of gout decreased with higher OBS. Diabetes may alter this negative correlation.

Fanzhang Meng

Siyi Lu

Yingzi Li

Chen Zhang

Tianlun Kang

Tangliang Qian

Chao Tan

Xiaoping Liu

Xiujuan Hou

Int J of Rheum Dis

Association between oxidative balance score and risk of gout: The NHANES cross‐sectional study, 2007–2018

Despite the established negative regulatory effects observed in various diseases like cardiovascular disease and diabetes, the distinct impact of red cell distribution width (RDW) to albumin ratio (RAR) on mortality within the realm of rheumatoid arthritis (RA) remains obscure. This study sought to explore the relationship between RAR and mortality in RA patients.

Zhi Liu

Red cell distribution width/albumin ratio and mortality risk in rheumatoid arthritis patients: Insights from a <scp>NHANES</scp> study

红细胞分布宽度/白蛋白比值与类风湿性关节炎患者死亡风险：基于NHANES研究的见解

Oxidative stress is associated with risk of pathogenesis between rheumatoid arthritis. The Oxidative Balance Score (OBS) is a systematic tool to assess the effects of diet and lifestyle in relation to oxidative stress. However, the association between OBS and rheumatoid arthritis has not been reported previously. We conducted a cross‐sectional study to investigate the complex association between OBS and rheumatoid arthritis in US adults.
Overall, 9747 participants were included in this cross‐sectional study. The exposure variable was OBS, which was scored by 16 dietary and four lifestyle factors. Multivariate logistic regression, subgroup analysis, and restricted cubic spline (RCS) regression were used to analyze the association between OBS and rheumatoid arthritis.
Compared to the lowest OBS quartile group (Q1), the multivariate corrected odds ratio (OR) (95% confidence interval [CI]) for the highest quartile of OBS (Q4) was 0.69 (0.52–0.90) (p= .013 for trend); furthermore, the RCS showed a negative linear relationship between OBS and rheumatoid arthritis. According to subgroup and RCS analyses, there was a significant difference between the association of OBS and with rheumatoid arthritis in terms of gender (p= .049).
In conclusion, high OBS was negatively associated with the risk of rheumatoid arthritis. Gender has an effect on OBS in RA. Our results suggest that OBS can be used as a biomarker to predict rheumatoid arthritis.

Leqing Li

Different gender of oxidative balance score on the risk of rheumatoid arthritis in the US population from NHANES

美国NHANES人群中氧化平衡评分不同性别对类风湿性关节炎风险的影响

Abstract Gout and hyperuricemia are common metabolic diseases. Patients with purine metabolism disorder and/or decreased uric acid excretion showed increased uric acid levels in the blood. The increase of uric acid in the blood leads to the deposition of urate crystals in tissues, joints, and kidneys, and causes gout. Recent studies have revealed that imbalance of the intestinal microecology is closely related to the occurrence and development of hyperuricemia and gout. Disorder of the intestinal flora often occurs in patients with gout, and high purine and high fructose may induce the disorder of intestinal flora. Short‐chain fatty acids and endotoxins produced by intestinal bacteria are closely related to the inflammatory response of gout. This article summarizes the characteristics of intestinal microecology in patients or animal models with hyperuricemia or gout, and explores the relationship between intestinal microecology and gout or hyperuricemia from the aspect of the intestinal barrier, intestinal microorganisms, intestinal metabolites, and intestinal immune system. We also review the current status of hyperuricemia treatment by targeting intestinal microecology.

Kai Dang

Nan Zhang

Haiqi Gao

Guifa Wang

Hui Liang

Meilan Xue

Influence of intestinal microecology in the development of gout or hyperuricemia and the potential therapeutic targets

肠道微生态在痛风或高尿酸血症发展中的影响及潜在治疗靶点

A key issue in the response to the coronavirus disease 2019 (COVID-19) pandemic is the internationally recognized observation that COVID-19 disproportionally affects the Black and minority ethnic population (BAME).1 We focus predominantly on UK, USA, and India COVID-19 rheumatology challenges and examples. This unprecedented public health crisis started in China in December 2019, following an infection caused by a novel coronavirus strain, named as SARS-CoV2.2 The World Health Organization in March 2020 declared this public health emergency as a pandemic.2 COVID-19 pandemic has moved from country to country, peaking at different times despite implementation of strict preventive measures, including complete lockdown periods with varied success. Case mortality rates have been highly variable across nations as well as different ethnic groups.3 A number of observational studies from UK and USA indicated that the death rate of COVID-19 is disproportionately higher in BAME.4, 5 The plausible reasons for increased mortality could be poor socio-economic status, poor housing, pre-existing comorbidity, obesity, and vitamin D deficiency.6, 7 The ongoing observations even implicate genetic variation in BAME groups for increased mortality.5 Some genetic differences may in fact be relevant such as variations in angiotensin-converting enzyme receptor levels in BAME patients8 and undiagnosed metabolic syndrome in South Asian communities may also be contributory, given that diabetes is such a key predisposition in the UK.9 Even among healthcare workers (HCW), where most of these factors may not be operative, the mortality has been higher in HCW from BAME backgrounds.8 Although data from the Office of National Statistics in the UK linked the increase deaths of BAME to age, gender, co-morbidities and occupation,9 the data remain inadequate.6 The variation in COVID-19 testing among BAME, HCW and front-line workers maybe a possible reason for increased reported deaths, as patients not admitted to hospital were not included initially in mortality figures.6 These observations need further investigation and the UK Government has initiated inquiry by Public Health England.6, 7 The increased migration from India, Pakistan, Bangladesh and other South Asian countries to developed countries such as UK and USA, with the USA particularly benefiting from the influx of Hispanic individuals, have played an important role in economic growth of these countries. However, the gaps in health inequalities among minorities were always there.4 In the USA, analyses of COVID-19 deaths from different states that house various ethnic populations revealed more deaths in Asians, Hispanics and African-Americans than in White Americans.4, 6 Many people from ethnic minorities hold critical skilled or unskilled jobs in health and social care, retail, public transport, and other sectors, putting them on the front line and at risk of exposure to COVID-19.6 Data from Australia, though, showed low mortality in general, but had higher representation in migrant populations.3 Surprisingly the death rate due to COVID-19 in India and other Asian countries is low relative to Western countries.10 Furthermore, the majority of patients are asymptomatic or have milder symptoms and need for intensive care support is lower compared to developed countries.10 The population of India (1 387 297 452) is 4 times that of the USA (331 002 651); however, the number of cases as well as deaths due to COVID-19 has been very low in India. On May 18, the WHO reported 3029 deaths in India among 96 169 total cases, which contrasts with USA, where 87 180 deaths have been reported among 1 432 265 cases.2 While under-reporting of cases due to non-reporting, low testing figures, higher false negative rates due to improper training of healthcare staff, as well as collection and handling of samples, are likely to have contributed, large numbers of deaths could not have gone unnoticed. Moreover, case fatality rates vary between different states (0.0%-9.1%), and it is impossible to factor in the differences that might result in the variation.6 For example, states reporting less than 0.5% to gross domestic product (GDP; equivalent to some of the African nations' total GDP) have no mortality.11 This means socio-economic factors may not fully explain the differences. There is perceptible stigma among the patients as well as healthcare workers as they don't come forward for testing; how this will affect the incidence and case fatality rates is difficult to compound.12 This is something similar to minority ethnic populations across the world.13 For sure the discrepancy between higher deaths in BAME in developed countries compared to countries of origin remain complex.3 Socio-economic deprivation gaps are heightened during these challenging times.10, 14 The increased deaths are also linked with pre-existing respiratory diseases in developed countries; however, respiratory diseases are more common in India.10 Clearly, there is disparity in COVID-19 deaths among ethnic minorities between developing and developed countries. Other than these medical reasons, bureaucratic issues and political pressures go unaccounted for in most reports.4 These global patterns present challenges for rheumatology communities serving populations from BAME backgrounds.13 Certain rheumatic diseases are more common among BAME groups, such as systemic lupus erythematosus (SLE).15, 16 Previous studies from the UK identified health inequalities in managing chronic diseases, such rheumatoid arthritis and SLE.17, 18 Studies demonstrated patient-related factors may play a key role in adherence to treatments among BAME rheumatology patients.19, 20 The patient-related factors noted in studies are similar to those from developing and developed countries.21, 22 A significant analytical challenge is that these patients are on various immunosuppressive treatments, which also increase the risk of infections.23 However, data suggest the medications used in rheumatology, such as tocilizumab and anakinra, may have some beneficial effect in COVID-19 patients.24, 25 Although trials and registries have been set up, BAME patients are usually under-represented. The Global COVID-19 Rheumatology registry is trying to overcome this.26 Being a global alliance, this might help us comprehend the complex interactions between COVID-19, rheumatological diseases and ethnic diversity.27 In the UK, rheumatology colleagues, together with patient rheumatology charities, acted independently of governmental efforts to reach out to BAME communities where English language proved to be a problem in understanding the guidelines around COVID-19.13 Working closely with policy makers, such as the British Society for Rheumatology, to collect departmental data on patient shielding was also an initiative taken by some of the authors. The UK Government developed a screening formula to identify those "at risk" for taking immunosuppressive treatment to be directed to shield for 12 weeks. As the lockdowns across countries release, the challenges for each country will vary. For example, in the USA, Black or African American minorities and Hispanic groups are less likely to have health insurance, with consequent reduced healthcare access.4 Moreover, in some cases the insurance policy benefits may be lost due to unemployment. Of course, there are many factors influencing baseline health status and subsequent access to health care. The casualization of the workforce, particularly younger persons, and particular trades, for example hospitality, has meant that in any downturn they become unemployed, yet may not be eligible for the same support. Furthermore, in places like Australia if a business was closed because of a lockdown or insufficient work, even though people may not be unemployed and will return to the business when it resumes, people are unable to access their sick leave. In other countries, public health insurance is enmeshed with employment, and may not be part of casual employment. Similarly, in India, the challenges to accessing health care due to loss of wages and lack of health insurance as well as disability allowances, and long-distance travel to reach a hospital, are overwhelming. In addition, there is limited availability of hydroxychloroquine and immunosuppressive drugs at local medical shops and hospitalization is difficult for serious patients as most hospitals are working at lower capacity and some are wary of admitting patients due to fear of COVID-19 infections. This has been further complicated by the lockdown and inability to access health facilities at tertiary care centers due to lack of public transport. It is arduous to get permission from administration to travel under prevailing circumstances. However, the silver lining is that many of our rheumatic disease patients are relatively young, therefore at working age. It is difficult to contemplate how these services will resume once lockdowns are relaxed; rheumatologists working as private practitioners will be unsure how to start their services and administrations in government hospitals are busy reorganizing scarce resources around tackling COVID-19 and non-COVID-19 emergencies. From the spotlight on the data and discussion above, we consider there are at least 3 areas that merit global prioritization. First, there is an urgent need to understand more deeply the reasons behind and implications of a disproportionately high clinical impact of COVID-19 on certain ethnic groups; second, there is public policy and how this should be framed within individual countries to adapt to needs of diverse population groups; third, there is the issue about communication of intelligence about COVID-19 to ethnic groups. Understanding the reasons for the initial evidence of excess mortality in BAME and minority groups is essential for the successful implementation of mitigation strategies, particularly if substantial disease emerges in the future. Epidemiologic and scientific studies may lead to more targeted health interventions.14 A range of different studies is needed to investigate this from the scientific and treatment perspective and from a global public health viewpoint. In the USA the National Institute of Minority Health and Disparities (NIMHD) is soliciting such studies.26 In the UK the National Institute of Health Research (NIHR) and the UK Research and Innovation (UKRI) are jointly calling for research proposals to investigate the evidence and impact of COVID-19 on ethnicity.6 Concerns are being voiced about the particularly high risk of healthcare and other key workers who belong to BAME groups, as well as more generally, the evidence of a poorer outcome from COVID-19 infection in people from BAME backgrounds. These studies should provide us the results for effective control and treatment. In order to achieve health equity in vulnerable groups it is essential that trials should include diverse participants who may be at high risk, and take cognizance of the factors that may impose added vulnerability for risk stratification. This is particularly important for patients with rheumatic diseases, wherein many conditions are linked to the immune system, and patients may be on multiple medications that include immunomodulatory as well as immunosuppressive therapy.24, 28 Additionally, these patients may have disease-induced frailty, all of which taken together are relevant for risk stratification, that may be heightened by ethnicity. Public policy can enhance health but should also incorporate ethnic-specific adjustments if it is not to exacerbate differences in health care.6, 29 Culturally adapted mental health services have been shown to be more effective compared to standard services, when applied to persons of color.28 Optimal promotion of health equity in minority groups can be achieved only by policies that express a level of cultural competence for the target community.7 This requires reasonable adjustments to accommodate individual, family and community ethnic-specific differences in order to promote health equity, especially at a time of this COVID-19 pandemic.13 Implementation and messaging of such policies should chime with the values of all sectors of the population. The COVID-19 pandemic requires an understanding of its effects and how it is spread, as well as the acceptance of such intelligence by minority ethnic people in order for the population in this group to comfortably adopt positive measures for personal safety as well as to limit the spread of infection. Adequate knowledge of COVID-19 that is delivered in an understandable and acceptable format to the recipient is a determinant for such behavior.12 It is through the communication of such knowledge in a way that is culturally competent, that is vital to its acceptance, with the assurance that minority populations may adapt to such positive behaviors as are required in this time of global crisis. Some of the authors have already developed partnerships of joined-up thinking between the National Rheumatoid Arthritis Society and Ambassadors for Ethnicity Health, in the UK, to communicate, disseminate and raise awareness of COVID-19 among the BAME populations.13 Similar interventions in other nations may prove to be of value. Looking into the future with COVID-19, 2021 and beyond, interdisciplinary and international collaborative research projects to investigate the impacts are required as it is difficult to extrapolate the findings to different societies. Furthermore, there is much to be learned from comparing and contrasting between different countries that will better inform the approach individual countries may take as well as our global response. Collaborative datasets, as well as exploiting existing data, are also necessary to better bridge the health inequalities in rheumatology and beyond.

Arumugam Moorthy

Shirish Dubey

Ash Samanta

Ade Adebajo

Amita Aggarwal

Avinash Jain

Nibha Jain

S. Sam Lim

Gail S. Kerr

Kanta Kumar

COVID‐19 and ethnicity: Spotlight on the global rheumatology issues in developing and developed countries

COVID‐19与种族：聚焦发展中和发达国家中的全球风湿病学问题

ABSTRACT Objective To use ultrasound technology to assess the deposition of urate crystals in the common lower limb tendons of patients with gout, providing additional imaging information for the management of these patients. Methods High‐frequency ultrasound was retrospectively used to evaluate urate crystal deposition in common lower limb tendons—quadriceps, patellar, and Achilles—in patients with gouty arthritis. Comparative statistical analysis was conducted among asymptomatic hyperuricemia patients and healthy individuals during the same period. Results Aggregates were detected in the tendons of all three groups, whereas tophi were found exclusively in tendons of asymptomatic hyperuricemia and gout groups. The prevalence of intratendinous aggregates and tophi in gout was significantly higher than the other groups ( p &lt; 0.05). The Achilles tendon showed the highest involvement, followed by the quadriceps and patellar tendons. Conclusion Tendons are common sites of urate deposition in patients with gout and asymptomatic hyperuricemia. Aggregates and tophi are frequently observed in and around large tendons such as the quadriceps, patellar, and Achilles tendons in gout patients. Ultrasonography proves useful in highly sensitive and specific evaluation of urate deposition within and around tendons.

Si‐Hui Deng

Jie Wang

Jing Hu

Bin Tu

Wan‐Tai Dang

Jian Liu

Ultrasonographic Evaluation of Urate Crystal Deposition in Tendons With Gout Patients

痛风患者肌腱尿酸盐晶体沉积的超声评估

Wenbo Zhang

Huihua Yuan

Xing Lv

Chunlin Huang

Haisheng Zeng

Dexin Liu

Nicola Ruperto

Huasong Zeng

Int J Rheum Dis

<scp>JIA</scp>, Today and Tomorrow

《交大》，昨天、今天和明天

Shi‐Hang Chen

Yuan Tang

Harry Asena Musonye

Hai‐Feng Pan

Global Burden of Diseases Dataset, Methodology and Its Use in Rheumatic and Musculoskeletal Diseases

全球疾病负担数据集、方法学及其在风湿性和肌肉骨骼疾病中的应用

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by the presence of autoantibodies against nuclear antigens and immune complex deposition. The pathogenesis of SLE is not fully understood; however, there are alterations in neutrophils and lymphocytes. Recent parameters assessing both neutrophil activations (Neut-RI, Neut-GI, IG) and activated lymphocytes (Re-Lymp, As-Lymp) can be used to assess the activation of immune cells. The aim of this study was to explore the potential role of this parameter in detecting active SLE.

Andri Iskandar Mardia

Laniyati Hamijoyo

Evan Susandi

Delita Prihatni

Bachti Alisjahbana

Amaylia Oehadian

The Potential Role of Neutrophil Reactivity Intensity and Reactive Lymphocytes as Extended Hematological Parameters to Detect Active Systemic Lupus Erythematosus

中性粒细胞反应强度和反应性淋巴细胞作为扩展血液学参数在检测活动性系统性红斑狼疮中的潜在作用

First reported in 2005, anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (anti-MDA5+) dermatomyositis (anti-MDA5+ DM) is thought to be rare and is often complicated by rapidly progressive interstitial lung disease (RP-ILD), resulting in poor prognosis [1]. Anti-MDA5+ DM has mainly been reported in Asian populations, mostly in China and Japan, but has been gaining increased attention worldwide, especially after the COVID-19 pandemic. The crucial problems in anti-MDA5+ DM management are stratifying patients according to their prognosis and exploring optimal therapeutics. This mini-review focuses on prognostic factors, the frontier of therapeutic strategies, and the recent progress in understanding their pathophysiology. Two recent meta-analyses showed similar results for the prognostic factors of anti-MDA5+ DM [2, 3]. The mortality risk associated with anti-MDA5+ DM increases with age. Many patients with anti-MDA5+ DM exhibit little muscle involvement but are characterized by skin and lung involvement. RP-ILD is a unique phenotype of anti-MDA5+ DM with a poor prognosis. However, skin lesions (heliotrope rash, Gottron's sign, skin erosions, and ulcers) were not associated with poor prognosis in anti-MDA5+ DM. Elevated lactate dehydrogenase (LDH), creatinine kinase, ferritin, C-reactive protein, lymphocytopenia, and anti-Ro 52 positivity predict mortality in patients with anti-MDA5+ DM. Studies have also reported the predictive value of several pro-inflammatory cytokines, including interleukin (IL)-6, IL-15, and IL-18 [2, 4]. Anti-MDA5 antibody serves not only as a diagnosis biomarker; quantification of anti-MDA5 antibody levels also appears to be useful for disease activity assessment and predicting treatment response [4]. Several prognostic models have been proposed to predict the mortality of patients with myositis and interstitial lung disease, including the FLAIR and MCK models [1, 5]. Additionally, the CROSS model effectively predicted the incidence of RP-ILD in patients with anti-MDA5+ DM [6]. Factors comprising these models, such as ferritin, LDH, C-reactive protein, and anti-Ro 52-antibody positivity, can be adopted for the mortality prediction of anti-MDA5+ DM. However, other aforementioned factors could also serve as supplements and should further be investigated in prospective studies. Immunosuppressive therapy is the mainstay treatment for MDA5 + DM patients, showing variable efficacy. Triple combination therapy comprising high-dose glucocorticoids, calcineurin inhibitors, and intravenous cyclophosphamide has demonstrated favorable survival rates in anti-MDA5+ DM patients compared with dual therapy (glucocorticoids in combination with calcineurin inhibitors or cyclophosphamide) or step-wise addition of these two immunosuppressants on the basis of high-dose glucocorticoids [7]. The effectiveness of triple combination therapy indicates the need to target lymphocytes with different functions and comprehensively block the inflammatory responses in patients with anti-MDA5+ DM. Therapies targeting autoantibody production or enhancing its clearance, including rituximab and therapeutic plasma exchange (TPE), have also been used in these patients. Several case series have reported clinical improvement in anti-MDA5+ DM patients, mostly with RP-ILD, after administration of rituximab [8]. However, the reported efficacy of rituximab varied in anti-MDA5+ DM between studies. Shirakashi et al. [9] reported that among 13 anti-MDA5+ DM patients who were resistant to the triple combination therapy, five of eight patients who received TPE survived, while untreated five patients died (p = 0.04) at an average of 2.4 months. Since then, TPE has been introduced as an adjuvant treatment [8]. Biological agents targeting inflammatory pathways, including IL-6 receptor antagonists and Janus kinase inhibitors (JAKi), have been used to treat patients with anti-MDA5+ DM, and successful results have been reported occasionally [10]. In a Chinese study, the JAKi protocol, using tofacitinib at a dose of 5 mg twice daily combined with glucocorticoids, significantly improved the survival of early-stage anti-MDA5+ DM patients [11]. However, direct comparisons between triple combination therapy and biological agents are lacking. The outcomes of patients with severe MDA5+ DM are still far from ideal. Effective therapeutic strategies should be explored in prospective trials. Anti-MDA5 dermatomyositis has occasionally been reported in patients with viral infections or malignant tumors. In addition, anti-MDA5 autoantibody positivity is not limited to dermatomyositis [12]. The presence of anti-MDA5 antibodies and clinical symptoms similar to those of anti-MDA5+ DM, including RP-ILD and lung injury, have been reported in severe COVID-19 patients [13]. Recently, we also reported an immune-related adverse event (irAE) case presenting as RP-ILD with anti-MDA5 antibody positivity in a patient with lung cancer, indicating that immune checkpoint inhibitors could be a trigger for the development of anti-MDA5+ RP-ILD [14]. Based on this evidences, autoantibodies directed against MDA5 likely connect different disease domains and endow patients with similar features, especially RP-ILD and poor prognosis. As a cytosolic pattern recognition receptor for viral RNA, MDA5 plays an essential role in anti-viral immune response by activating the IFN pathway. Plasma IFN-α levels were found to be increased in anti-MDA5+ DM patients, compared with patients suffering from other types of DM. Recently, Ye et al. [15] reported that type I IFN signaling is overstimulated in peripheral B cells and T cells obtained from patients with anti-MDA5+ DM, using single-cell RNA sequencing. Moreover, they identified pro-fibrotic response via type I IFN signaling in the affected lung tissue samples [15]. Besides, the IFN signature has been identified in the skin, and muscle of patients with anti-MDA5+ DM [16]. These findings suggest a crucial role of type I IFN pathway in the pathogenesis of anti-MDA5+ DM. This common pathway may explain the similar presentations observed in different clinical scenarios. The pathogenic effect of the anti-MDA5 antibody has not been fully established. A recent study identified lung injury after treating human MDA5 transgenic mice with rabbit anti-human MDA5 polyclonal antibodies [17]. Meanwhile, Ichimura et al. recently demonstrated in a mouse model, that the combination of MDA5-immunization and administration of poly (I:C), a mimicker of viral infection, but not MDA5-immunization alone, resulted in the development of ILD [18]. Therefore, we speculate that anti-MDA5 antibodies could trigger the ILD development in the presence of several factors, such as infections and drugs in genetically susceptible patients. Type I IFN activation in sequence aims at fighting against these triggers but also triggers uncontrolled immune responses, including dysregulated biomarkers and immune cells, resulting in damage to different organs (lung, skin, and muscle), as seen in anti-MDA5+ DM (Figure 1). Studies have shown that a considerable number of patients with anti-MDA5+ DM die during the first 6 months of onset, and survivors could anticipate extended survival, which is supposed to be related to fluctuations in Type I IFN signaling pathway activation [2]. In conclusion, anti-MDA5 antibody positivity may be shared among patients with inflammatory diseases, infectious diseases, and cancer. Anti-MDA5+ autoantibodies could represent overly uncontrolled activation of the IFN pathway. This might expand our understanding of this syndrome and its underlying mechanisms, which will shed light on the lives of patients with anti-MDA5+ DM. All authors contributed to the conception of this article. Huaiya Xie drafted the manuscript. Junping Fan critically revised the manuscript. Luo Wang and Xinlun Tian provided significant revisions to the manuscript. All authors approved the final version of the manuscript and agreed to be accountable for all aspects of the work. The authors have nothing to report. The authors declare no conflicts of interest. The authors confirm that the data supporting the findings of this study are available within the article.

Huaiya Xie

Luo Wang

Junping Fan

Xinlun Tian

Behind Anti‐<scp>MDA5</scp> Antibody: Symbol of A Specific Disease or A Phenomenon?

抗-MDA5抗体背后：特定疾病的标志还是一种现象？

Abbreviation	Int J of Rheum Dis
Journal Impact	2.55
Quartiles(Global)	RHEUMATOLOGY(Q2)

ISSN	1756-1841, 1756-185X
h-index	57

Publication Information	Publisher: John Wiley and Sons Inc，Publishing cycle: Quarterly，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2008，Proportion of original research papers: 79.08%，Self Citation Rate:20.80%， Gold OA Rate: 9.08%
Average review cycle	网友分享经验：平均3月
Average recruitment ratio	网友分享经验：较易

International Journal of Rheumatic Diseases

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