Inborn errors of immunity (IEI) are immune system disorders caused by genetic mutations, often presenting with varying degrees of infection, immune dysregulation, lymphoproliferation, and tumor susceptibility. Initially, IEIs were typically diagnosed in patients with recurrent and unusual infections. However increasing research has shown that noninfectious manifestations can also be the initial or even primary presentation of IEI. Over the past ten years, more and more IEIs associated with autoinflammatory symptoms have been identified. Although these diseases are rare, relevant research suggests that immune deficiency and autoinflammation are not opposing conditions but rather interconnected aspects of the immune system, influencing each other in a complementary and inseparable manner. This article reviews the mechanisms involved in IEI with autoinflammation, and proposes some clues for identifying IEI manifested as autoinflammation. It also summarizes the current progress in the diagnosis and treatment of IEI manifested as autoinflammation, and presents prospects for future research on IEI.

Immuno-actinopathies are hereditary diseases characterized by immunodeficiency and immune dysregulation due to the mutations in single genes which are regulating actin remodeling. Mutations in actin-related regulatory genes can lead to functional defects in actin activation, extension, branching, transcription and others. The mutations also affect the cytoskeleton and pseudopod formation; then they further affect the functions of immune cell, resulting in cell deformation, motility, phagocytosis, and adhesion. The clinical manifestations vary, including infection, autoimmunity, autoinflammatory, and susceptibility to tumors, making the detection and diagnosis difficult. The pathogenic mechanisms of some of the related diseases have been preliminarily elucidated. Future research will focus on the identification of new immunoactinopathy-caused genes and its mechanism, discovery of new precision therapeutic target, development of drugs, improvement of hematopoietic stem cell transplantation strategies, and discovery of new gene therapy. Immuno-actinopathies have a low incidence rate with diversified clinical manifestations so that they are easy to be misdiagnosed and missed. This article reviews the pathogenic gene defects of actinopathies and their clinical manifestations in detail that are valuable to clinical reference.

Kidney is one of the key target organs involved in autoinflammatory diseases (AIDs). The clinical manifestations of renal impairment associated with AIDs are diverse, including hematuria, proteinuria, nephrotic syndrome, hypertension, renal artery stenosis, renal insufficiency, and others. The pathogenesis is mostly renal amyloidosis and/or renal vasculitis/vasculopathy caused by inflammasome activation. Whether or not the kidney is involved and its degree is closely related to the prognosis of AIDs patients. This article introduces the pathogenesis of AIDs-related renal impairmen and highlights the clinical characteristics of renal damage in some AIDs, aiming to enhance clinicians′ understanding of AIDs-related renal damage, and to implement early diagnosis and treatment to improve patients′ quality of life and prognosis.

Signal transduction and activator of transcription factor 1(STAT1), one of the important members of the STAT family, is a key cytoplasmic transcription factor and an important component of the JAK-STAT signaling pathway. Gain-of-function mutations in STAT1 (STAT1-GOF) impaired the dephosphorylation of STAT1 protein, mediated the enhancement of cell signaling pathways such as type Ⅰ, Ⅱ, and Ⅲ interferon(IFN) and interleukins-27 (IL-27), IL-6, IL-10, and IL-17, and inhibited Th17 cells. The clinical manifestations of STAT1-GOF are diverse, including chronic mucocutaneous candidiasis and autoimmune diseases. For the treatment of STAT1-GOF, such as targeted therapy with ruxolitinib for STAT1 hyperphosphorylation, immunomodulatory therapy and hematopoietic stem cell transplantation for different self-immune systems, certain curative effects can be obtained. With the understanding of disease mechanisms and the discovery of new clinical phenotypes, this review focuses on the diseases caused by gain-of-function mutations of STAT1, and introduces the clinical manifestations and treatment progress of STAT1-GOF to promote the understanding of such diseases and their future diagnosis, treatment and research works.

Rare diseases have a significant and profound impact on society, the economy, and the healthcare system. The path to developing drugs for rare diseases is particularly arduous. Due to the small number of patients and limited market demand, pharmaceutical companies don′t have enough incentives and resources to invest in drug research and development. Additionally, the long development cycles, high costs, and high risks have led to a number of potential therapeutic drug failures at the early stages of development. This article summarizes a series of encouraging policies adopted by the National Medical Products Administration for rare diseases, which is an important public health issue, as well as the achievements in the review and approval of rare disease drugs in recent years. These policies have accelerated the approval process. Meanwhile, the policies ensure the safety and effectiveness of drugs and offer more treatment options and hopes to patients with rare diseases. With the continuous effort at optimizing the policy environment and the advancement of research and development technologies, China′s drug regulatory authorities will continue to focus on the clinical needs of rare diseases, to implement " patient-centered " approach to drug development, inject new vitality into the research and development of drugs of rare diseases, and offer more precise and effective treatment choices for patients with rare diseases.

Schimke immuno-osseous dysplasia (SIOD)caused by SMARCAL1 gene mutations is a rare genetic disorder characterized by multi-system involvement, including T-cell dysfunction, skeletal dysplasia, disproportionate short stature, nephrotic syndrome, and kidney failure. This multidisciplinary consultation involved a 9-year-old boy with intrauterine growth retardation, presenting with short stature, T-cell lymphopenia, proteinuria, and degenerative bone and joint disease. Treatment primarily focused on symptomatic and supportive care. Through the multidisciplinary rare disease consultation, holistic support was provided to the patient, offering comprehensive care from various specialtiesx.We also aim to use this case report to enhance clinicians′ under-standing of SIOD and improve the management and treatment of rare diseases.

Type Ⅰ interferonopathy is an autoinflammatory disease that affects multiple systems, with a high disability and mortality rate. It profoundly impacts the quality of life of patients and poses a considerable burden on their families and society. Due to the broad spectrum of clinical phenotypes associated with this condition, early identification remains challenging. Delays in diagnosis and treatment can exacerbate the disease, making it difficult to reverse the conditions and adversely affecting the prognosis. Therefore, the Chinese Alliance of Pediatric Rheumatic & Immunologic Diseases and Chinese Pharmacists Association Rare Diseases Medication Working Committee has developed this consensus document to offer detailed recommendations pertaining to the definition, genetic categorization, clinical presentations, diagnostic approaches, and therapeutic management of type Ⅰ interferonopathy.