Nature Reviews Disease Primers最新文献

Alopecia areata is a common cause of non-scaring autoimmune hair loss, associated with substantial psychosocial burden. Alopecia areata is an autoimmune disease in which loss of immune privilege in hair follicles leads to local hair follicle-associated inflammation. A chronic disease with uncertain course that is estimated to affect 2% of people over their lifetime, alopecia areata can present with a range of clinical features, from a single small round patch of hair loss to full scalp and body hair loss, and is associated with atopic, autoimmune and psychological comorbidities. Alopecia areata also has a major negative impact on quality of life, with a greater mental burden than physical burden. Since the 2010s, advances in understanding of disease pathogenesis have led to the identification of inflammatory pathways that can be successfully inhibited to produce substantial clinical responses. The therapeutic landscape has been transformed, with FDA approval of the first treatment for adults with severe alopecia areata in 2022 and for adolescents with severe alopecia areata in 2023, with multiple investigational treatments currently in phase II and phase III clinical trials.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory pathogen that emerged in December 2019 and caused a global pandemic by March 2020, with >7 million deaths due to coronavirus disease 2019 (COVID-19) globally as of September 2025. The clinical syndrome of COVID-19 ranges from asymptomatic infection to severe disease with pneumonia and death. SARS-CoV-2 variant type, inoculum, previous exposure and host factors influence the clinical trajectory. Identification of key structural proteins of SARS-CoV-2 and insights into the pathophysiology of the immune response to infection led to the development of effective preventive (vaccines and monoclonal antibodies) and therapeutic (antivirals and immunomodulatory agents) agents. Antiviral agents, such as remdesivir and nirmatrelvir-ritonavir, inhibit viral replication and immunomodulatory agents, such as tocilizumab and baricitinib, act to reduce a dysregulated immune response to SARS-CoV-2. The pandemic had economic and socio-cultural consequences that affected the quality of life and overall life expectancy of individuals. As the emergency phase of the pandemic concludes, robust monitoring and surveillance systems must be sustained and research to improve vaccines and therapeutics must continue to maintain control of SARS-CoV-2 in the population and be prepared for emerging pathogens with pandemic potential.

Androgenetic alopecia (AGA) is a condition of scalp hair growth characterized by progressive miniaturization of hair follicles and a reduction in the number of active follicles. In general, frontal, mid-scalp and crown hair follicles in postpubescent men and in postmenopausal women are susceptible to AGA. In rare cases, premenopausal women and prepubescent individuals are affected. In men, AGA is hypothesized to be caused by increased androgen signalling within susceptible hair follicles, altering the levels of locally produced signalling factors that sustain hair growth, whereas the molecular basis of AGA in women remains undetermined. AGA displays variability in its time of onset, severity and distribution patterns, and genome-wide association studies have uncovered more than 380 genomic loci associated with AGA, including genes involved in androgen and WNT pathways. Furthermore, epidemiological studies support substantial ancestral variation in AGA. Effective therapies for AGA include autologous transplantation of androgen-resistant occipital hair follicles, oral finasteride and topical minoxidil. Not all individuals with AGA respond to these therapies or comply with daily use of medicines, creating a need for new approaches. Emerging therapies for AGA include hair follicle-activating peptides, mRNA-containing liposomes, as well as bioengineering of new hair follicles. AGA has a negative socioemotional effect on affected individuals, and its prompt diagnosis and treatment can improve self-reported quality of life.

Listeriosis is a serious food-borne bacterial infection caused by Listeria monocytogenes. L. monocytogenes is a facultative intracellular bacterial species that can replicate inside human cells, as well as thrive in a variety of environments, including soil, decaying vegetation, animal intestines and foods such as unpasteurized dairy products, soft cheese, raw meat, fish, seafood, vegetables and fruits. Clinically, L. monocytogenes can cause gastroenteritis in healthy individuals or serious invasive infections in at-risk populations. For example, maternal-fetal infections during pregnancy can lead to adverse pregnancy outcomes. In the elderly and immunosuppressed, listeriosis can cause septicaemia and central nervous system infections (also known as neurolisteriosis) with high mortality and risk of long-term sequelae. Genomic studies have identified four lineages of L. monocytogenes, with lineage I comprising the most virulent strains. The pathogenicity of L. monocytogenes reflects its ability to resist gastric and bile acids, colonize the intestinal lumen, cross the intestinal barrier, survive intracellularly in the bloodstream, evade immune responses, and cross the placental and blood-brain barriers. Diagnosis of listeriosis (septicaemia, neurolisteriosis, maternal-neonatal listeriosis or focal listeriosis) involves clinical observations and microbiological testing based on bacterial culture or DNA detection in individuals with prior antimicrobial therapy. Treatment typically involves aminopenicillins and aminoglycosides, with no evidence of clinically meaningful acquired antimicrobial resistance. Although listeriosis is a well-studied infection, a clearer picture of its global burden, its pathophysiology, the dynamics of the L. monocytogenes population and transmission routes is needed. On the host side, new risk factors, including genetics, and new treatment regimens to improve patient outcomes need to be identified.

Lupus nephritis (LN) is a type of glomerulonephritis and one of the most serious complications of systemic lupus erythematosus (SLE). LN affects 25-60% of patients with SLE, with incidence and prevalence varying by age, sex, ethnicity and socioeconomic factors. LN predominantly develops within 5 years of an SLE diagnosis and, for many patients, it is the initial manifestation that leads to the recognition of SLE. In some patients, LN may develop late in the disease course, highlighting the importance of persistent awareness of its symptoms and signs. Despite an increasing understanding of disease biology and more effective treatment options, LN remains a substantial cause of morbidity and mortality as it can lead to irreversible kidney failure and associated complications. Risk factors for progression to kidney failure include persistent proteinuria, low glomerular filtration rate, hypertension at diagnosis and frequent disease flares. LN pathogenesis involves complex immune dysregulation, with key pathways including type I interferon signalling, calcineurin activation, and B and T cell dysfunction. Several immunomodulatory drugs are used for the management of LN, and treatment paradigms are increasingly shifting towards multi-agent regimens. Along with appropriate pharmacotherapy, multidisciplinary care tailored to the patient's individual needs, involving rheumatologists, nephrologists, social workers and other health professionals, is crucial for holistically addressing both the immune and non-immune risk factors for progressive kidney function loss and for maximizing kidney lifespan in LN.