Using social risks to predict unplanned hospital readmission and emergency care among hospitalized Veterans.

OBJECTIVES: (1) To estimate the association of social risk factors with unplanned readmission and emergency care after a hospital stay. (2) To create a social risk scoring index. DATA SOURCES AND SETTING: We analyzed administrative data from the Department of Veterans Affairs (VA) Corporate Data Warehouse. Settings were VA medical centers that participated in a national social work staffing program. STUDY DESIGN: We grouped socially relevant diagnoses, screenings, assessments, and procedure codes into nine social risk domains. We used logistic regression to examine the extent to which domains predicted unplanned hospital readmission and emergency department (ED) use in 30 days after hospital discharge. Covariates were age, sex, and medical readmission risk score. We used model estimates to create a percentile score signaling Veterans' health-related social risk. DATA EXTRACTION: We included 156,690 Veterans' admissions to a VA hospital with discharged to home from 1 October, 2016 to 30 September, 2022. PRINCIPAL FINDINGS: The 30-day rate of unplanned readmission was 0.074 and of ED use was 0.240. After adjustment, the social risks with greatest probability of readmission were food insecurity (adjusted probability = 0.091 [95% confidence interval: 0.082, 0.101]), legal need (0.090 [0.079, 0.102]), and neighborhood deprivation (0.081 [0.081, 0.108]); versus no social risk (0.052). The greatest adjusted probabilities of ED use were among those who had experienced food insecurity (adjusted probability 0.28 [0.26, 0.30]), legal problems (0.28 [0.26, 0.30]), and violence (0.27 [0.25, 0.29]), versus no social risk (0.21). Veterans with social risk scores in the 95th percentile had greater rates of unplanned care than those with 95th percentile Care Assessment Needs score, a clinical prediction tool used in the VA. CONCLUSIONS: Veterans with social risks may need specialized interventions and targeted resources after a hospital stay. We propose a scoring method to rate social risk for use in clinical practice and future research.

Building Tailored Resource Guides to Address Social Risks and Advance Health Equity in the Veterans Health Administration.

Background: Health care organizations, including the Veterans Health Administration (VHA), are increasingly adopting programs to address social determinants of health. As part of a comprehensive social risk screening and referral model, tailored resource guides can support efforts to address unmet social needs. However, limited guidance is available on best practices for the development of resource guides in health care settings. Observations: This article describes the development of geographically tailored resource guides for a national VHA quality improvement initiative, Assessing Circumstances and Offering Resources for Needs (ACORN), which aims to systematically screen for and address social needs among veterans. We outline the rationale for using resource guides as a social needs intervention and provide a pragmatic framework for resource guide development and maintenance. We offer guidance based on lessons learned from the development of ACORN resource guides, emphasizing a collaborative approach with VHA social workers and other frontline clinical staff, as well as with community-based organizations. Our how-to guide provides steps for identifying high-yield resources along with formatting considerations to maximize accessibility and usability among patients. Conclusions: Resource guides can serve as a valuable cross-cutting component of health care organizations' efforts to address social needs. We provide a practical approach to resource guide development that may support successful implementation within the VHA and other clinical settings.

The potential of artificial intelligence to revolutionize health care delivery, research, and education in cardiac electrophysiology.

The field of electrophysiology (EP) has benefited from numerous seminal innovations and discoveries that have enabled clinicians to deliver therapies and interventions that save lives and promote quality of life. The rapid pace of innovation in EP may be hindered by several challenges including the aging population with increasing morbidity, the availability of multiple costly therapies that, in many instances, confer minor incremental benefit, the limitations of healthcare reimbursement, the lack of response to therapies by some patients, and the complications of the invasive procedures performed. To overcome these challenges and continue on a steadfast path of transformative innovation, the EP community must comprehensively explore how artificial intelligence (AI) can be applied to healthcare delivery, research, and education and consider all opportunities in which AI can catalyze innovation; create workflow, research, and education efficiencies; and improve patient outcomes at a lower cost. In this white paper, we define AI and discuss the potential of AI to revolutionize the EP field. We also address the requirements for implementing, maintaining, and enhancing quality when using AI and consider ethical, operational, and regulatory aspects of AI implementation. This manuscript will be followed by several perspective papers that will expand on some of these topics.

Multisystemic Effects of Elexacaftor-Tezacaftor-Ivacaftor in Adults with Cystic Fibrosis and Advanced Lung Disease.

Rationale: Limited data exist on the safety and effectiveness of elexacaftor-tezacaftor-ivacaftor (ETI) in people with cystic fibrosis (pwCF) and advanced lung disease. Objectives: To evaluate the effects of ETI in an unselected population of pwCF and advanced lung disease. Methods: A prospective observational study, including all adults aged 18 years and older with percentage predicted forced expiratory volume in 1 second (ppFEV1) ⩽ 40 who initiated ETI from December 2019 to June 2021 in France, was conducted. PwCF were followed until August 8, 2022. Results: ETI was initiated in 434 pwCF with a median ppFEV1 of 30 (interquartile range, 25-35), including 27 with severe cystic fibrosis liver disease and 183 with diabetes. PwCF were followed for a median of 587 (interquartile range, 396-728) days after ETI initiation. Discontinuation of ETI occurred in 12 (2.8%) pwCF and was due mostly to lung transplantation (n = 5) or death (n = 4). Absolute increase in ppFEV1 by a mean of +14.2% (95% confidence interval, 13.1-15.4%) occurred at 1 month and persisted throughout the study. Increase in ppFEV1 in the youngest age quartile was almost twice that of the oldest quartile (P < 0.001); body mass index < 18.5 kg/m2 was found in 38.6% at initiation versus 11.3% at 12 months (P = 0.0001). Increases in serum concentrations of vitamins A and E, but not 25-hydroxy vitamin D3, were observed. Significant reductions in the percentages of pwCF using oxygen therapy, noninvasive ventilation, nutritional support, and inhaled and systemic therapies (including antibiotics) were observed; insulin was discontinued in 12% of patients with diabetes. Conclusions: ETI is safe in pwCF and advanced lung disease, with multisystem pulmonary and extrapulmonary benefits.

Artificial Intelligence in Cardiovascular Care-Part 2: Applications: JACC Review Topic of the Week.

Recent artificial intelligence (AI) advancements in cardiovascular care offer potential enhancements in effective diagnosis, treatment, and outcomes. More than 600 U.S. Food and Drug Administration-approved clinical AI algorithms now exist, with 10% focusing on cardiovascular applications, highlighting the growing opportunities for AI to augment care. This review discusses the latest advancements in the field of AI, with a particular focus on the utilization of multimodal inputs and the field of generative AI. Further discussions in this review involve an approach to understanding the larger context in which AI-augmented care may exist, and include a discussion of the need for rigorous evaluation, appropriate infrastructure for deployment, ethics and equity assessments, regulatory oversight, and viable business cases for deployment. Embracing this rapidly evolving technology while setting an appropriately high evaluation benchmark with careful and patient-centered implementation will be crucial for cardiology to leverage AI to enhance patient care and the provider experience.

Artificial Intelligence for Cardiovascular Care-Part 1: Advances: JACC Review Topic of the Week.

Recent artificial intelligence (AI) advancements in cardiovascular care offer potential enhancements in diagnosis, treatment, and outcomes. Innovations to date focus on automating measurements, enhancing image quality, and detecting diseases using novel methods. Applications span wearables, electrocardiograms, echocardiography, angiography, genetics, and more. AI models detect diseases from electrocardiograms at accuracy not previously achieved by technology or human experts, including reduced ejection fraction, valvular heart disease, and other cardiomyopathies. However, AI's unique characteristics necessitate rigorous validation by addressing training methods, real-world efficacy, equity concerns, and long-term reliability. Despite an exponentially growing number of studies in cardiovascular AI, trials showing improvement in outcomes remain lacking. A number are currently underway. Embracing this rapidly evolving technology while setting a high evaluation benchmark will be crucial for cardiology to leverage AI to enhance patient care and the provider experience.

Advancing Wearable Biosensors for Congenital Heart Disease: Patient and Clinician Perspectives: A Science Advisory From the American Heart Association.

Wearable biosensors (wearables) enable continual, noninvasive physiologic and behavioral monitoring at home for those with pediatric or congenital heart disease. Wearables allow patients to access their personal data and monitor their health. Despite substantial technologic advances in recent years, issues with hardware design, data analysis, and integration into the clinical workflow prevent wearables from reaching their potential in high-risk congenital heart disease populations. This science advisory reviews the use of wearables in patients with congenital heart disease, how to improve these technologies for clinicians and patients, and ethical and regulatory considerations. Challenges related to the use of wearables are common to every clinical setting, but specific topics for consideration in congenital heart disease are highlighted.

The gut microbiota posttranslationally modifies IgA1 in autoimmune glomerulonephritis.

Mechanisms underlying the disruption of self-tolerance in acquired autoimmunity remain unclear. Immunoglobulin A (IgA) nephropathy is an acquired autoimmune disease where deglycosylated IgA1 (IgA subclass 1) auto-antigens are recognized by IgG auto-antibodies, forming immune complexes that are deposited in the kidneys, leading to glomerulonephritis. In the intestinal microbiota of patients with IgA nephropathy, there was increased relative abundance of mucin-degrading bacteria, including Akkermansia muciniphila. IgA1 was deglycosylated by A. muciniphila both in vitro and in the intestinal lumen of mice. This generated neo-epitopes that were recognized by autoreactive IgG from the sera of patients with IgA nephropathy. Mice expressing human IgA1 and the human Fc α receptor I (α1KI-CD89tg) that underwent intestinal colonization by A. muciniphila developed an aggravated IgA nephropathy phenotype. After deglycosylation of IgA1 by A. muciniphila in the mouse gut lumen, IgA1 crossed the intestinal epithelium into the circulation by retrotranscytosis and became deposited in the glomeruli of mouse kidneys. Human α-defensins-a risk locus for IgA nephropathy-inhibited growth of A. muciniphila in vitro. A negative correlation observed between stool concentration of α-defensin 6 and quantity of A. muciniphila in the guts of control participants was lost in patients with IgA nephropathy. This study demonstrates that gut microbiota dysbiosis contributes to generation of auto-antigens in patients with IgA nephropathy and in a mouse model of this disease.

Reversal of cylindrical bronchial dilatations in a subset of adults with cystic fibrosis treated with elexacaftor-tezacaftor-ivacaftor.

BACKGROUND: This study sought to evaluate the impact of elexacaftor-tezacaftor-ivacaftor (ETI) on lung structural abnormalities in adults with cystic fibrosis (awCF) with a specific focus on the reversal of bronchial dilatations. METHODS: Chest computed tomography (CT) performed prior to, and ≥12 months after initiation of ETI were visually reviewed for possible reversal of bronchial dilatations. AwCF with and without reversal of bronchial dilatation (the latter served as controls with 3 controls per case) were selected. Visual Brody score, bronchial and arterial diameters, and lung volume were measured on CT. RESULTS: Reversal of bronchial dilatation was found in 12/235 (5%) awCF treated with ETI. Twelve awCF with and 36 without reversal of bronchial dilatations were further analyzed (male=56%, mean age=31.6±8.5 years, F508del/F508del CFTR =54% and mean %predicted forced expiratory volume in 1 s=58.8%±22.3). The mean±sd Brody score improved overall from 79.4±29.8 to 54.8±32.3 (p<0.001). Reversal of bronchial dilatations was confirmed by a decrease in bronchial lumen diameter in cases from 3.9±0.9 mm to 3.2±1.1 mm (p<0.001), whereas it increased in awCF without reversal of bronchial dilatation (from 3.5±1.1 mm to 3.6±1.2 mm, p=0.002). Reversal of bronchial dilatations occurred in cylindrical (not varicose or saccular) bronchial dilatations. Lung volumes decreased by -6.6±10.7% in awCF with reversal of bronchial dilatation but increased by +2.3±9.6% in controls (p=0.007). CONCLUSION: Although bronchial dilatations are generally considered irreversible, ETI was associated with reversal, which was limited to the cylindrical bronchial dilatations subtype, and occurred in a small subset of awCF. Initiating ETI earlier in life may reverse early bronchial dilatations.

Patient Priorities Care Increases Long-Term Service and Support Use: Propensity Match Cohort Study.

OBJECTIVES: Patient priorities care (PPC) is an evidence-based approach designed to help patients achieve what matters most to them by identifying their health priorities and working with clinicians to align the care they provide to the patient's priorities. This study examined the impact of the PPC approach on long-term service and support (LTSS) use among veterans. DESIGN: Quasi-experimental study examining differences in LTSS use between veterans exposed to PPC and propensity-matched controls not exposed to PPC adjusting for covariates. SETTING AND PARTICIPANTS: Fifty-six social workers in 5 Veterans Health Administration (VHA) sites trained in PPC in 2018, 143 veterans who used the PPC approach, and 286 matched veterans who did not use the PPC approach. METHODS: Veterans with health priorities identified through the PPC approach were the intervention group (n = 143). The usual care group included propensity-matched veterans evaluated by the same social workers in the same period who did not participate in PPC (n = 286). The visit with the social worker was the index date. We examined LTSS use, emergency department (ED), and urgent care visits, 12 months before and after this date for both groups. Electronic medical record notes were extracted with a validated natural language processing algorithm (84% sensitivity, 95% specificity, and 92% accuracy). RESULTS: Most participants were white men, mean age was 76, and 30% were frail. LTSS use was 48% higher in the PPC group compared with the usual care group [odds ratio (OR), 1.48; 95% CI, 1.00-2.18; P = .05]. Among those who lived >2 years after the index date, new LTSS use was higher (OR, 1.69; 95% CI, 1.04-2.76; P = .036). Among nonfrail individuals, LTSS use was also higher in the PPC group (OR, 1.70; 95% CI, 1.06-2.74; P = .028). PPC was not associated with higher ED or urgent care use. CONCLUSIONS AND IMPLICATIONS: PPC results in higher LTSS use but not ED or urgent care in these veterans. LTSS use was higher for nonfrail veterans and those living longer. The PPC approach helps identify health priorities, including unmet needs for safe and independent living that LTSS can support.

Promises and Perils of Consumer Mobile Technologies in Cardiovascular Care: JACC Scientific Statement.

Direct-to-consumer (D2C) wearables are becoming increasingly popular in cardiovascular health management because of their affordability and capability to capture diverse health data. Wearables may enable continuous health care provider-patient partnerships and reduce the volume of episodic clinic-based care (thereby reducing health care costs). However, challenges arise from the unregulated use of these devices, including questionable data reliability, potential misinterpretation of information, unintended psychological impacts, and an influx of clinically nonactionable data that may overburden the health care system. Further, these technologies could exacerbate, rather than mitigate, health disparities. Experience with wearables in atrial fibrillation underscores these challenges. The prevalent use of D2C wearables necessitates a collaborative approach among stakeholders to ensure effective integration into cardiovascular care. Wearables are heralding innovative disease screening, diagnosis, and management paradigms, expanding therapeutic avenues, and anchoring personalized medicine.

Update on Cardiovascular Implantable Electronic Device Infections and Their Prevention, Diagnosis, and Management: A Scientific Statement From the American Heart Association: Endorsed by the International Society for Cardiovascular Infectious Diseases.

The American Heart Association sponsored the first iteration of a scientific statement that addressed all aspects of cardiovascular implantable electronic device infection in 2010. Major advances in the prevention, diagnosis, and management of these infections have occurred since then, necessitating a scientific statement update. An 11-member writing group was identified and included recognized experts in cardiology and infectious diseases, with a career focus on cardiovascular infections. The group initially met in October 2022 to develop a scientific statement that was drafted with front-line clinicians in mind and focused on providing updated clinical information to enhance outcomes of patients with cardiovascular implantable electronic device infection. The current scientific statement highlights recent advances in prevention, diagnosis, and management, and how they may be incorporated in the complex care of patients with cardiovascular implantable electronic device infection.

Estudo da ativação e modulação da resposta imune contra a esporotricose experimental, a partir de vesículas extracelulares purificadas de células dendríticas / Study of the activation and modulation of the immune response against experimental sporotrichosis, using extracellular vesicles purified from dendritic cells

A esporotricose é uma zoonose micótica emergente e subcutânea, que afeta a pele, o sistema linfático e outros órgãos de humanos e animais. Assim como outras doenças infecciosas fúngicas, se torna ainda mais grave quando acomete pacientes imunossuprimidos. Essa infecção possui distribuição global e é endêmica em algumas regiões do Brasil e de outros países tropicais e subtropicais, sendo um problema de saúde pública importante em nosso país. A doença é causada por um complexo de pelo menos quatro espécies patogênicas, incluindo o Sporothrix brasiliensis (S. brasiliensis). A resposta imunológica contra estas espécies ainda não é completamente elucidada, mas estruturas como as vesículas extracelulares (VEs) poderiam transportar componentes importantes que podem contribuir na modulação e no controle desta importante infecção. Assim, o objetivo deste trabalho, é analisar a participação das VEs de células dendríticas (DCs) naive e VEs de DCs previamente primadas com leveduras de S. brasiliensis e primadas com VEs do fungo, na resposta imune contra a esporotricose experimental em modelos murinos. Para isso, as DCs obtidas da medula óssea de camundongos, foram cultivadas com leveduras de S. brasiliensis ou com VEs do fungo e posteriormente, VEs totais das DCs foram purificadas a partir de ultracentrifugação e analisadas quanto a sua participação na modulação da resposta imunológica. Essas VEs foram utilizadas em protocolo profilático em modelos murinos, previamente a infecção subcutânea experimental. Foi observado o diâmetro médio das lesões no decorrer de 35 dias de infecção e a carga fúngica da lesão na pele. Os resultados obtidos mostram que as VEs de DCs naive, e VEs de DCs previamente cultivadas com leveduras do fungo ou com VEs fúngicas, são capazes de modular a carga fúngica. Os grupos que receberam VEs de DCs de forma profilática, de modo geral apresentaram diminuição significativa da carga fúngica em relação ao grupo controle. Na análise comparativa apenas dos grupos que receberam a profilaxia, observa-se que o uso de VEs de DCs naive, resultam em uma carga fúngica maior que o uso de VEs de DCs previamente ativadas, e quando as DCs são ativadas com levedura, essa carga fúngica é a menor. Quando analisamos o perfil de citocinas na pele de camundongos tratados com as VEs previamente a infecção, observamos aumento de IFN-γ, TNF-α, IL-17 e IL-10 principalmente nos animais previamente tratados com VEs de DCs que foram ativadas com leveduras. Em relação às citocinas produzidas, podemos sugerir até o momento, uma resposta imunológica mista, mas que de alguma maneira, ainda não esclarecida, devem contribuir para melhor controle do processo infeccioso in vivo. Em relação a linfoproliferação, observa-se principalmente um aumento de linfócitos T CD4+ quando acrescentamos VEs de DCs que não foram previamente ativadas, mostrando uma ação de uma resposta mais inespecífica. Vale ressaltar que todos os protocolos profiláticos foram capazes de modular e minimizar o crescimento fúngico, quando comparados ao controle, ou seja, as VEs contribuíram com o controle da infecção e agiram a favor do hospedeiro, demonstrando um caráter protetivo

Sporotrichosis is an emerging subcutaneous mycotic zoonosis that affects the skin, lymphatic system, and other organs of humans and animals, and like other infectious fungal diseases, it becomes even more serious when it affects immunosuppressed patients. This infection has a global distribution and is endemic in some regions of Brazil and other tropicals and subtropicals countries, being an important public health problem in our country. The disease is caused by a complex of at least four pathogenic species, including Sporothrix brasiliensis (S. brasiliensis). The immunological response against these species has not yet been completely elucidated, but structures such as extracellular vesicles (EVs) could carry important components that can contribute to the modulation and control of this important infection. Thus, the objective of this work is to analyze the participation of EVs from naïve dendritic cells (DCs) and EVs from DCs previously primed with S. brasiliensis yeast and primed with EVs from the fungus, in the immune response against experimental sporotrichosis in murine models. For this, DCs obtained from the bone marrow of mice were cultivated with S. brasiliensis yeast or EVs from the fungus, and subsequently, total EVs from the DCs were purified through ultracentrifugation and analyzed for their participation in modulating the immune response. These EVs were used in a prophylactic protocol in murine models, before experimental subcutaneous infection. The average diameter of the lesions over 35 days of infection and the fungal load of the lesion on the skin were observed. The results obtained show that EVs from naïve DCs, and EVs from DCs previously cultured with yeast or fungal EVs, are capable of modulating the fungal load. The groups that received EVs from DCs prophylactically generally showed a significant decrease in fungal load compared to the control group. In the comparative analysis of only the groups that received prophylaxis, it was observed that the use of EVs from naïve DCs results in a higher fungal load than the use of EVs from previously activated DCs, and when the DCs are activated with yeast, this load fungal is smaller. When we analyzed the cytokine profile in the skin of mice treated with EVs before infection, we observed an increase in IFN-γ, TNF-α, IL-17, and IL-10, mainly in animals previously treated with EVs from DCs that were activated with yeast. About the cytokines produced, we can so far suggest a mixed immunological response, but in some way, not yet clear, they should contribute to better control of the infectious process in vivo. About lymphoproliferation, an increase in CD4+ T lymphocytes is mainly observed when we add EVs from DCs that were not previously activated, showing a more nonspecific response. It is worth highlighting that all prophylactic protocols were able to modulate and minimize fungal growth, when compared to the control, that is, EVs contributed to the control of the infection and acted in favor of the host, demonstrating a protective character

Benefits and challenges in the use of RE-AIM for evaluation of a national social work staffing program in the veterans health administration.

Background: In the Department of Veterans Affairs (VA) Veterans Health Administration (VHA), social workers embedded in primary care teams address social and emotional needs that are associated with health outcomes. The mission of the National Social Work PACT Staffing Program is to improve access to social work services for rural Veterans by supporting additional social work staffing in VA medical centers serving rural areas. Methods: We obtained data from the VA corporate data warehouse on Veterans' characteristics and health care use from 2016 to 2022 for all Veterans who received primary care at a Veterans Affairs Medical Center (VAMC) or associated clinic that received funding from the program. We evaluated the program according to RE-AIM constructs as follows: Reach [total number of Veterans who engaged with PACT social work and representativeness with regard to race, rural residence, chronic conditions and health behaviors, and hospital and emergency department (ED) use in the previous 12 months]; Effectiveness (impact of the program on key health care use outcomes which include hospitalizations, emergency department visits, and palliative care); Adoption (number of VA medical centers and outpatient clinics serving rural Veterans that have participated in the program, and number and representativeness of sites eligible for program participation that have not yet received funding); Implementation (adherence to standardized note templates), and Maintenance (permanent social work positions created by the program and continued technical support). Results: In 2022, the program engaged with 30,982 Veterans, 65% of whom lived in rural areas. The program increased social work encounters, reduce hospital and emergency department use, and increase use of palliative care services among Veterans. Key elements of implementation include proactive outreach to Veterans with high-risk indicators and assessment for social risk factors using standardized, national note templates. In terms of maintenance, the program continues to provide data and technical assistance to 23 sites and has created 171 permanent social work positions. Conclusions and implications: The Social Work PACT Staffing Program demonstrates positive outcomes and program sustainment. The RE-AIM framework was a useful tool to evaluate the program, but additional adaption was needed to fit the program's needs.

Frequency, Markers and Costs of Secondary Bacterial Infection in Pediatric Dengue.

BACKGROUND: Secondary bacterial infection (SBI) occurs in a proportion of individuals with dengue and results in longer hospitalization, higher mortality, and increased health-related costs. However, the frequency, risk factors and predictive biomarkers of this comorbidity in pediatric dengue is partially known. METHODS: We conducted a retrospective multicenter study in a dengue hyperendemic region of Colombia, analyzing 1597 children from two pediatric cohorts. We included children with confirmed dengue (mild to severe disease) and evaluated the rate of SBI, their clinical characteristics, diagnostic predictors and attention costs. We also assessed the diagnostic performance of plasma interleukin (IL)-6 for detecting SBI in pediatric dengue. RESULTS: The frequency of SBI in children with dengue with warning signs in cohorts 1 and 2 was 2.4% and 7.3%, respectively, and this rate reached 30.7% and 38.2% in children with severe disease. Staphylococcus aureus and Escherichia coli were the more frequent infectious agents. Increased total leukocytes and C-reactive protein levels, as well as high IL-6 at hospital admission, in children <48 months of age were early indications of SBI in dengue. Higher rates of organ dysfunction, the requirement of a longer hospitalization and a 2.3-fold increase in attention costs were observed in SBI. CONCLUSIONS: An important proportion of children with dengue course with SBI and exhibit higher morbidity. Elevated leukocytes, C-reactive protein and IL-6 in young children are early markers of SBI. Physicians should identify children with dengue and risk factors for SBI, microbiologically confirm the bacterial infection, and rationally and timely provide antimicrobial therapy.

MAIT cells altered phenotype and cytotoxicity in lupus patients are linked to renal disease severity and outcome.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease in which circulating immune complexes can cause different types of glomerulonephritis, according to immune deposits and to the type of glomerular cell injury. Proliferative lesions represent the most severe form of lupus nephritis (LN) and often lead to kidney failure and death. Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells that recognize microbial-derived ligands from the riboflavin synthesis pathway. Although abundant in peripheral blood, MAIT cells are enriched in mucosal and inflamed tissues. While previous studies have reported concordant results concerning lower MAIT cell frequencies in the blood of SLE patients, no information is known about MAIT cell function and LN severity and outcome. Methods: In the current study, we analyzed the baseline phenotype and function of peripheral blood MAIT cells by flow cytometry in 26 patients with LN and in a control group of 16 healthy individuals. Results: We observe that MAIT cell frequencies are markedly reduced in blood of LN patients. MAIT cells from patients have an altered phenotype in terms of migration, proliferation and differentiation markers, notably in most severe forms of LN. Frequencies of PMA/ionomycin stimulated MAIT cells secreting effector molecules, such as proinflammatory IL-17 and cytotoxic protein granzyme B, are higher in LN patients. Patients undergoing a complete renal remission after immunosuppressive therapy had higher MAIT cell frequency, lower expression of proliferation marker Ki-67 and granzyme B (GzB) at inclusion. Remarkably, GzB production defines a predictive model for complete remission. Discussion: We report here that blood MAIT cells display proinflammatory and cytotoxic function in severe lupus nephritis which may play a pathogenesis role, but without association with systemic lupus activity. Finally, low cytotoxic profile of MAIT cells may represent a promising prognostic factor of lupus nephritis remission one year after induction therapy.