Differences in management approaches for lupus nephritis within the UK.

Objectives: Outcomes of therapy for LN are often suboptimal. Guidelines offer varied options for treatment of LN and treatment strategies may differ between clinicians and regions. We aimed to assess variations in the usual practice of UK physicians who treat LN. Methods: We conducted an online survey of simulated LN cases for UK rheumatologists and nephrologists to identify treatment preferences for class IV and class V LN. Results: Of 77 respondents, 48 (62.3%) were rheumatologists and 29 (37.7%) were nephrologists. A total of 37 (48.0%) reported having a joint clinic between nephrologists and rheumatologists, 54 (70.0%) reported having a multidisciplinary team meeting for LN and 26 (33.7%) reported having a specialized lupus nurse. Of the respondents, 58 (75%) reported arranging a renal biopsy before starting the treatment. A total of 20 (69%) of the nephrologists, but only 13 (27%) rheumatologists, reported having a formal departmental protocol for treating patients with LN (P < 0.001). The first-choice treatment of class IV LN in pre-menopausal patients was MMF [41 (53.2%)], followed by CYC [15 (19.6%)], rituximab [RTX; 12 (12.5%)] or a combination of immunosuppressive drugs [9 (11.7%)] with differences between nephrologists' and rheumatologists' choices (P = 0.026). For class V LN, MMF was the preferred initial treatment, irrespective of whether proteinuria was in the nephrotic range or not. RTX was the preferred second-line therapy for non-responders. Conclusion: There was variation in the use of protocols, specialist clinic service provision, biopsies and primary and secondary treatment choices for LN reported by nephrologists and rheumatologists in the UK.

Everyone Wins: Vaccine Lotteries Can Cost-Effectively Increase COVID-19 Booster Vaccination Rates.

Booster vaccination remains a key strategy to address the ongoing threat of coronavirus disease 2019 (COVID-19). However, take-up has been slow. By the fall of 2022, less than 50% of eligible US residents had received a booster dose. It is a central tenet in health economics that incentives or penalties are necessary to reach optimal vaccination rates. Six rigorous real-world studies provide evidence that COVID-19 vaccine lotteries cost-effectively raised vaccination rates at an estimated cost of $49 to $82 per additional dose. The 5 studies that found no impact of lotteries used statistical methods that underestimated the impact: They were statistically underpowered to detect a small yet cost-effective impact and did not adequately address selection bias. Vaccine lotteries are cost-effective because they not only provide financial incentives but also influence the public via nonfinancial channels: They garner media attention, tap into social networks, combat procrastination, and signal the importance of sustaining high vaccination rates. In fact, vaccine lotteries are likely to be more effective for booster vaccination than for initial doses because barriers to vaccination are higher. The ongoing threat of COVID-19 presents a unique opportunity to develop and implement innovative, evidence-based public health policies like vaccine lotteries to address current challenges.

Data-driven COVID-19 policy is more effective than a one-size-fits-all approach.

The latest COVID-19 guidelines from the Centers for Disease Control and Prevention (CDC) discount the best data sources and rely too heavily on outdated, one-size-fits-all decision rules. Instead, the CDC should recommend data-driven guidelines, which are more accurate, adaptable, transparent about implicit tradeoffs, and tailored to the relevant context.

Real world treatment of juvenile-onset systemic lupus erythematosus: Data from the UK JSLE cohort study.

BACKGROUND: In the absence of clinical trials evidence, Juvenile-onset Systemic Lupus Erythematosus (JSLE) treatment plans vary. AIM: To explore 'real world' treatment utilising longitudinal UK JSLE Cohort Study data. METHODS: Data collected between 07/2009-05/2020 was used to explore the choice/sequence of immunomodulating drugs from diagnosis. Multivariate logistic regression determined how organ-domain involvement (pBILAG-2004) impacted treatment choice. RESULT: 349 patients met inclusion criteria, median follow-up 4-years (IQR:2,6). Mycophenolate mofetil (MMF) was most commonly used for the majority of organ-domains, and significantly associated with renal involvement (OR:1.99, 95% CI:1.65-2.41, pc < 0.01). Analyses assessing the sequence of immunomodulators focused on 197/349 patients (meeting relevant inclusion/exclusion criteria). 10/197 (5%) solely recieved hydroxychloroquine/prednisolone, 62/197 (31%) received a single-immunomodulator, 69/197 (36%) received two, and 36/197 patients (28%) received ≥three immunomodulators. The most common first and second line immunomodulator was MMF. Rituximab was the most common third-line immunomodulator. CONCLUSIONS: Most UK JSLE patients required ≥two immunomodulators, with MMF used most commonly.

Attainment of low disease activity and remission targets reduces the risk of severe flare and new damage in childhood lupus.

OBJECTIVES: To assess the achievability and effect of attaining low disease activity (LDA) or remission in childhood-onset SLE (cSLE). METHODS: Attainment of three adult-SLE derived definitions of LDA (LLDAS, LA, Toronto-LDA), and four definitions of remission (clinical-SLEDAI-defined remission on/off treatment, pBILAG-defined remission on/off treatment) was assessed in UK JSLE Cohort Study patients longitudinally. Prentice-Williams-Petersen gap recurrent event models assessed the impact of LDA/remission attainment on severe flare/new damage. RESULTS: LLDAS, LA and Toronto-LDA targets were reached in 67%, 73% and 32% of patients, after a median of 18, 15 or 17 months, respectively. Cumulatively, LLDAS, LA and Toronto-LDA was attained for a median of 23%, 31% and 19% of total follow-up-time, respectively. Remission on-treatment was more common (61% cSLEDAI-defined, 42% pBILAG-defined) than remission off-treatment (31% cSLEDAI-defined, 21% pBILAG-defined). Attainment of all target states, and disease duration (>1 year), significantly reduced the hazard of severe flare (P < 0.001). As cumulative time in each target increased, hazard of severe flare progressively reduced. LLDAS attainment reduced the hazard of severe flare more than LA or Toronto-LDA (P < 0.001). Attainment of LLDAS and all remission definitions led to a statistically comparable reduction in the hazards of severe flare (P > 0.05). Attainment of all targets reduced the hazards of new damage (P < 0.05). CONCLUSIONS: This is the first study demonstrating that adult-SLE-derived definitions of LDA/remission are achievable in cSLE, significantly reducing risk of severe flare/new damage. Of the LDA definitions, LLDAS performed best, leading to a statistically comparable reduction in the hazards of severe flare to attainment of clinical remission.

Neutrophils in the Pathogenesis of Rheumatoid Arthritis and Systemic Lupus Erythematosus: Same Foe Different M.O.

Dysregulated neutrophil activation contributes to the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Neutrophil-derived reactive oxygen species (ROS) and granule proteases are implicated in damage to and destruction of host tissues in both conditions (cartilage in RA, vascular tissue in SLE) and also in the pathogenic post-translational modification of DNA and proteins. Neutrophil-derived cytokines and chemokines regulate both the innate and adaptive immune responses in RA and SLE, and neutrophil extracellular traps (NETs) expose nuclear neoepitopes (citrullinated proteins in RA, double-stranded DNA and nuclear proteins in SLE) to the immune system, initiating the production of auto-antibodies (ACPA in RA, anti-dsDNA and anti-acetylated/methylated histones in SLE). Neutrophil apoptosis is dysregulated in both conditions: in RA, delayed apoptosis within synovial joints contributes to chronic inflammation, immune cell recruitment and prolonged release of proteolytic enzymes, whereas in SLE enhanced apoptosis leads to increased apoptotic burden associated with development of anti-nuclear auto-antibodies. An unbalanced energy metabolism in SLE and RA neutrophils contributes to the pathology of both diseases; increased hypoxia and glycolysis in RA drives neutrophil activation and NET production, whereas decreased redox capacity increases ROS-mediated damage in SLE. Neutrophil low-density granulocytes (LDGs), present in high numbers in the blood of both RA and SLE patients, have opposing phenotypes contributing to clinical manifestations of each disease. In this review we will describe the complex and contrasting phenotype of neutrophils and LDGs in RA and SLE and discuss their discrete roles in the pathogenesis of each condition. We will also review our current understanding of transcriptomic and metabolomic regulation of neutrophil phenotype in RA and SLE and discuss opportunities for therapeutic targeting of neutrophil activation in inflammatory auto-immune disease.

Does Access to Family Planning Increase Children's Opportunities? Evidence from the War on Poverty and the Early Years of Title X.

This paper examines the relationship between parents' access to family planning and the economic resources of their children. Using the county-level introduction of U.S. family planning programs between 1964 and 1973, we find that children born after programs began had 2.8% higher household incomes. They were also 7% less likely to live in poverty and 12% less likely to live in households receiving public assistance. A bounding exercise suggests that the direct effects of family planning programs on parents' resources account for roughly two-thirds of these gains.

Do Incarcerated Populations Serve as a Reservoir for Tuberculosis in South Africa?

Tuberculosis (TB) prevalence among incarcerated populations is as much as 1,000 times higher than in the general population. This study evaluates whether correctional facilities serve as a reservoir through which TB is transmitted to surrounding communities. Tuberculosis test data were extracted from the South African National Health Laboratory Service database for patients tested for TB between 2005 and 2011. We conducted graphical analysis to assess the relationship of TB rates between incarcerated and non-incarcerated populations over time. We performed generalized linear modeling with a log link function to assess TB risk in communities surrounding correctional facilities, net of confounders. We assessed linkages between incarcerated and non-incarcerated populations over time using Granger causality analysis. Tuberculosis prevalence among incarcerated populations was four times higher than in the general population. Tuberculosis incidence rates in incarcerated and non-incarcerated populations followed similar trends over time. The presence of a correctional facility in a municipality was associated with 34.9% more detected TB cases (confidence interval: 11.6-63.2; P < 0.01), controlling for potential confounders. Detected TB in incarcerated populations did not have predictive power in explaining detected TB rates in the non-incarcerated population after controlling for serial correlation in the time series data. Despite high TB prevalence, trends in correctional facilities do not appear to be driving temporal trends in the general population. However, correctional facilities still act as a TB reservoir that raises the overall TB risk in the vicinity. Intensified TB control policies for correctional facilities, formerly incarcerated individuals, and surrounding communities will reduce TB prevalence overall.

The Impact of Anti-Retroviral Therapy on Tuberculosis Detection at the National Level in South Africa.

Human immunodeficiency virus/tuberculosis (HIV/TB) coinfection is particularly prevalent in South Africa, where TB has been the leading cause of death for more than a decade. The 2004-2008 national rollout of antiretroviral therapy (ART) provides a unique opportunity to examine the population-level impact of ART on the TB epidemic. We performed longitudinal regression analysis to follow the evolution of TB outcomes before and after the introduction of ART using a large data set from the National Health Laboratory Service. This is the first study to produce estimates of the impact of the ART rollout by exploiting staggered timing and geographic variation in the rollout. After ART became available in a health facility, 3.7% (P < 0.0001) more patients were tested for TB and 3.2% (P < 0.0001) more received repeat testing; however, there was a steep rise in testing before the introduction of ART. Although the number of TB-positive patients increased by 4.3% (P = 0.0002) in the first year post-ART, the TB rate among tested patients fell by 2 percentage points (8%, P = 0.001) after 2 years. Sputum smear testing declined relative to more technologically advanced diagnostics post-ART. Antiretroviral therapy availability increased the attention to TB screening and drew new patients into the health-care system. Small increases in the numbers of repeat patients are indicative of retention in care. The decline in TB rates post-ART suggests that the reduction in TB risk due to improved immune functioning and health-care contact likely outweighed the increased TB risk because of the longer lifespan of ART initiators.

Cost effectiveness of medical devices to diagnose pre-eclampsia in low-resource settings.

BACKGROUND: Maternal mortality remains a major health challenge facing developing countries, with pre-eclampsia accounting for up to 17 percent of maternal deaths. Diagnosis requires skilled health providers and devices that are appropriate for low-resource settings. This study presents the first cost-effectiveness analysis of multiple medical devices used to diagnose pre-eclampsia in low- and middle-income countries (LMICs). METHODS: Blood pressure and proteinuria measurement devices, identified from compendia for LMICs, were included. We developed a decision tree framework to assess the cost-effectiveness of each device using parameter values that reflect the general standard of care based on a survey of relevant literature and expert opinion. We examined the sensitivity of our results using one-way and second-order probabilistic multivariate analyses. RESULTS: Because the disability-adjusted life years (DALYs) averted for each device were very similar, the results were influenced by the per-use cost ranking. The most cost-effective device combination was a semi-automatic blood pressure measurement device and visually read urine strip test with the lowest combined per-use cost of $0.2004 and an incremental cost effectiveness ratio of $93.6 per DALY gained relative to a baseline with no access to diagnostic devices. When access to treatment is limited, it is more cost-effective to improve access to treatment than to increase testing rates or diagnostic device sensitivity. CONCLUSIONS: Our findings were not sensitive to changes in device sensitivity, however they were sensitive to changes in the testing rate and treatment rate. Furthermore, our results suggest that simple devices are more cost-effective than complex devices. The results underscore the desirability of two design features for LMICs: ease of use and accuracy without calibration. Our findings have important implications for policy makers, health economists, health care providers and engineers.

An econometric method for estimating population parameters from non-random samples: An application to clinical case finding.

The problem of sample selection complicates the process of drawing inference about populations. Selective sampling arises in many real world situations when agents such as doctors and customs officials search for targets with high values of a characteristic. We propose a new method for estimating population characteristics from these types of selected samples. We develop a model that captures key features of the agent's sampling decision. We use a generalized method of moments with instrumental variables and maximum likelihood to estimate the population prevalence of the characteristic of interest and the agents' accuracy in identifying targets. We apply this method to tuberculosis (TB), which is the leading infectious disease cause of death worldwide. We use a national database of TB test data from South Africa to examine testing for multidrug resistant TB (MDR-TB). Approximately one quarter of MDR-TB cases was undiagnosed between 2004 and 2010. The official estimate of 2.5% is therefore too low, and MDR-TB prevalence is as high as 3.5%. Signal-to-noise ratios are estimated to be between 0.5 and 1. Our approach is widely applicable because of the availability of routinely collected data and abundance of potential instruments. Using routinely collected data to monitor population prevalence can guide evidence-based policy making.

Assessing healthcare quality using routine data: evaluating the performance of the national tuberculosis programme in South Africa.

OBJECTIVE: To assess the performance of healthcare facilities by means of indicators based on guidelines for clinical care of TB, which is likely a good measure of overall facility quality. METHODS: We assessed quality of care in all public health facilities in South Africa using graphical, correlation and locally weighted kernel regression analysis of routine TB test data. RESULTS: Facility performance falls short of national standards of care. Only 74% of patients with TB provided a second specimen for testing, 18% received follow-up testing and 14% received drug resistance testing. Only resistance testing rates improved over time, tripling between 2004 and 2011. National awareness campaigns and changes in clinical guidelines had only a transient impact on testing rates. The poorest performing facilities remained at the bottom of the rankings over the period of study. CONCLUSION: The optimal policy strategy requires both broad-based policies and targeted resources to poor performers. This approach to assessing facility quality of care can be adapted to other contexts and also provides a low-cost method for evaluating the effectiveness of proposed interventions. Devising targeted policies based on routine data is a cost-effective way to improve the quality of public health care provided.

A Data-Driven Evaluation of the Stop TB Global Partnership Strategy of Targeting Key Populations at Greater Risk for Tuberculosis.

OBJECTIVE: Identifying those infected with tuberculosis (TB) is an important component of any strategy for reducing TB transmission and population prevalence. The Stop TB Global Partnership recently launched an initiative with a focus on key populations at greater risk for TB infection or poor clinical outcomes, due to housing and working conditions, incarceration, low household income, malnutrition, co-morbidities, exposure to tobacco and silica dust, or barriers to accessing medical care. To achieve operational targets, the global health community needs effective, low cost, and large-scale strategies for identifying key populations. Using South Africa as a test case, we assess the feasibility and effectiveness of targeting active case finding to populations with TB risk factors identified from regularly collected sources of data. Our approach is applicable to all countries with TB testing and census data. It allows countries to tailor their outreach activities to the particular risk factors of greatest significance in their national context. METHODS: We use a national database of TB test results to estimate municipality-level TB infection prevalence, and link it to Census data to measure population risk factors for TB including rates of urban households, informal settlements, household income, unemployment, and mobile phone ownership. To examine the relationship between TB prevalence and risk factors, we perform linear regression analysis and plot the set of population characteristics against TB prevalence and TB testing rate by municipality. We overlay lines of best fit and smoothed curves of best fit from locally weighted scatter plot smoothing. FINDINGS: Higher TB prevalence is statistically significantly associated with more urban municipalities (slope coefficient ß1 = 0.129, p < 0.0001, R2 = 0.133), lower mobile phone access (ß1 = -0.053, p < 0.001, R2 = 0.089), lower unemployment rates (ß1 = -0.020, p = 0.003, R2 = 0.048), and a lower proportion of low-income households (ß1 = -0.048, p < 0.0001, R2 = 0.084). Municipalities with more low-income households also have marginally higher TB testing rates, however, this association is not statistically significant (ß1 = -0.025, p = 0.676, R2 = 0.001). There is no relationship between TB prevalence and the proportion of informal settlement households (ß1 = 0.021, p = 0.136, R2 = 0.014). CONCLUSIONS: These analyses reveal that the set of characteristics identified by the Global Plan as defining key populations do not adequately predict populations with high TB burden. For example, we find that higher TB prevalence is correlated with more urbanized municipalities but not with informal settlements. We highlight several factors that are counter-intuitively those most associated with high TB burdens and which should therefore play a large role in any effective targeting strategy. Targeting active case finding to key populations at higher risk of infection or poor clinical outcomes may prove more cost effective than broad efforts. However, these results should increase caution in current targeting of active case finding interventions.

Does directly observed therapy improve tuberculosis treatment? More evidence is needed to guide tuberculosis policy.

BACKGROUND: Tuberculosis (TB) now ranks alongside HIV as the leading infectious disease cause of death worldwide and incurs a global economic burden of over $12 billion annually. Directly observed therapy (DOT) recommends that TB patients complete the course of treatment under direct observation of a treatment supporter who is trained and overseen by health services to ensure that patients take their drugs as scheduled. Though the current WHO End TB Strategy does not mention DOT, only "supportive treatment supervision by treatment partners", many TB programs still use it despite the fact that the has not been demonstrated to be statistically significantly superior to self-administered treatment in ensuring treatment success or cure. DISCUSSION: DOT is designed to promote proper adherence to the full course of drug therapy in order to improve patient outcomes and prevent the development of drug resistance. Yet over 8 billion dollars is spent on TB treatment each year and thousands undergo DOT for all or part of their course of treatment, despite the absence of rigorous evidence supporting the superior effectiveness of DOT over self-administration for achieving drug susceptible TB (DS-TB) cure. Moreover, the DOT component burdens patients with financial and opportunity costs, and the potential for intensified stigma. To rigorously evaluate the effectiveness of DOT and identify the essential contributors to both successful treatment and minimized patient burden, we call for a pragmatic experimental trial conducted in real-world program settings, the gold standard for evidence-based health policy decisions. It is time to invest in the rigorous evaluation of DOT and reevaluate the DOT requirement for TB treatment worldwide. Rigorously evaluating the choice of treatment supporter, the frequency of health care worker contact and the development of new educational materials in a real-world setting would build the evidence base to inform the optimal design of TB treatment protocol. Implementing a more patient-centered approach may be a wise reallocation of resources to raise TB cure rates, prevent relapse, and minimize the emergence of drug resistance. Maintaining the status quo in the absence of rigorous supportive evidence may diminish the effectiveness of TB control policies in the long run.

Equity in the national rollout of public AIDS treatment in South Africa 2004-08.

Low- and middle-income country governments face the challenge of ensuring an equitable distribution of public resources, based on need rather than socioeconomic status, race or political affiliation. This study examines factors that may influence public service provision in developing countries by analysing the 2004-08 implementation of government-provided AIDS treatment in South Africa, the largest programme of its kind in the world. Despite assurances from the National Department of Health, some have raised concerns about whether the rollout was in fact conducted equitably. This study addresses these concerns. This is the first study to assemble high-quality national data on a broad set of census main place (CMP) characteristics that the public health, economic and political science literature have found influence public service provision. Multivariate logistic regression and duration (survival) analysis were used to identify characteristics associated with a more rapid public provision of anti-retroviral therapy (ART) in South Africa. Overall, no clear pattern emerges of the rollout systematically favouring better-off CMPs, and in general the magnitude of statistically significant associations is small. The centralization of the early phases of the rollout to maximize ART enrolment led to higher ART coverage rates in areas where district and regional hospitals were located. Ultimately, these results demonstrate that the provision of life-saving AIDS treatment was not disproportionately delayed in disadvantaged areas. The combination of a clear policy objective, limited bureaucratic discretion and monitoring by civil society ensured equitable access to AIDS treatment. This work highlights the potential for future public investment in South Africa and other developing countries to reduce health and economic disparities.

Distance decay and persistent health care disparities in South Africa.

BACKGROUND: Access to health care is a particular concern given the important role of poor access in perpetuating poverty and inequality. South Africa's apartheid history leaves large racial disparities in access despite post-apartheid health policy to increase the number of health facilities, even in remote rural areas. However, even when health services are provided free of charge, monetary and time costs of travel to a local clinic may pose a significant barrier for vulnerable segments of the population, leading to overall poorer health. METHODS: Using newly available health care utilization data from the first nationally representative panel survey in South Africa, together with administrative geographic data from the Department of Health, we use graphical and multivariate regression analysis to investigate the role of distance to the nearest facility on the likelihood of having a health consultation or an attended birth. RESULTS: Ninety percent of South Africans live within 7 km of the nearest public clinic, and two-thirds live less than 2 km away. However, 14% of Black African adults live more than 5 km from the nearest facility, compared to only 4% of Whites, and they are 16 percentage points less likely to report a recent health consultation (p < 0.01) and 47 percentage points less likely to use private facilities (p < 0.01). Respondents in the poorest income quintiles live 0.5 to 0.75 km further from the nearest health facility (p < 0.01). Racial differentials in the likelihood of having a health consultation or an attended birth persist even after controlling for confounders. CONCLUSIONS: Our results have two policy implications: minimizing the distance that poor South Africans must travel to obtain health care and improving the quality of care provided in poorer areas will reduce inequality. Much has been done to redress disparities in South Africa since the end of apartheid but progress is still needed to achieve equity in health care access.

Understanding the relationship between access to care and facility-based delivery through analysis of the 2008 Ghana Demographic Health Survey.

OBJECTIVE: To determine the types of access to care most strongly associated with facility-based delivery among women in Ghana. METHODS: Data relating to the "5 As of Access" framework were extracted from the 2008 Ghana Demographic Health Survey and analyzed using multivariate logistic regression. RESULTS: In all, 55.5% of a weighted sample of 1102 women delivered in a healthcare facility, whereas 45.5% delivered at home. Affordability was the strongest access factor associated with delivery location, with health insurance coverage tripling the odds of facility delivery. Availability, accessibility (except urban residence), acceptability, and social access variables were not significant factors in the final models. Social access variables, including needing permission to seek healthcare and not being involved in decisions regarding healthcare, were associated with a reduced likelihood of facility-based delivery when examined individually. Multivariate analysis suggested that these variables reflected maternal literacy, health insurance coverage, and household wealth, all of which attenuated the effects of social access. CONCLUSION: Affordability was an important determinant of facility delivery in Ghana-even among women with health insurance-but social access variables had a mediating role.

The role of neutrophil apoptosis in juvenile-onset systemic lupus erythematosus.

OBJECTIVE: Accumulation of apoptotic cells may lead to the development of systemic lupus erythematosus (SLE) through a breakdown in immune tolerance. Altered neutrophil apoptosis may contribute to nuclear autoantigen exposure, ultimately leading to autoantibody generation. This study aimed to determine whether neutrophil apoptosis is altered in patients with juvenile-onset SLE as compared with controls. METHODS: Apoptosis was measured in neutrophils from patients with juvenile-onset SLE (n=12), adult-onset SLE (n=6), and pediatric patients with inflammatory (n=12) and noninflammatory (n=12) conditions. Annexin V staining and flow cytometry were used to determine neutrophil apoptosis. Proapoptotic and antiapoptotic proteins were measured in sera and in neutrophil cell lysates. RESULTS: Neutrophil apoptosis was significantly increased in patients with juvenile-onset SLE as compared with the noninflammatory controls at time 0. Incubation of neutrophils with sera from patients with juvenile-onset SLE further increased neutrophil apoptosis as compared with incubation with sera from pediatric controls. Concentrations of TRAIL and FasL were significantly increased in sera from patients with juvenile-onset SLE, whereas interleukin-6, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly decreased. Addition of GM-CSF to sera from patients with juvenile-onset SLE significantly decreased neutrophil apoptosis as compared with juvenile-onset SLE sera alone. The expression of proapoptotic proteins (caspase 3, Fas, and FADD) was elevated in juvenile-onset SLE neutrophils, whereas the expression of antiapoptotic proteins (cellular inhibitor of apoptosis 1 and 2 and X-linked inhibitor of apoptosis) was decreased. Neutrophil apoptosis correlated with biomarkers of disease activity (erythrocyte sedimentation rate and double-stranded DNA concentration) and the British Isles Lupus Assessment Group disease activity score. CONCLUSION: Our data demonstrate an imbalance in proapoptotic and antiapoptotic factors in both neutrophils and sera from patients with juvenile-onset SLE. This imbalance results in increased neutrophil apoptosis in these patients. Correlations with markers of disease activity indicate that altered neutrophil apoptosis in juvenile-onset SLE patients may play a pathogenic role in this condition.