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1.
Curr Opin Rheumatol ; 36(5): 336-343, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38990100

RESUMO

PURPOSE OF REVIEW: Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is often organ- or life-threatening in children and impacts them during important periods of psychosocial and physical development. This review covers recent advances in the pathophysiology, diagnosis, management, and outcomes of AAV in children and highlights the ongoing need for funding and increased research collaboration. RECENT FINDINGS: Recent work has improved our understanding of AAV disease pathogenesis, potentially identifying new biomarkers and therapeutic targets. Collaborative clinical studies have also highlighted the variable manifestations in children and identified potential factors associated with poorer outcomes. Consensus-based treatment guidelines are also appearing, but clinical trials are still essential to better understanding treatment efficacy and safety in children affected by AAV. New, validated outcome measures, including those that are patient-reported, will facilitate these much-needed clinical trials in pediatric AAV. SUMMARY: There is a continued need for more rigorous study in pediatric AAV, however, there is certainly excitement with the increase in recent research relevant to the pediatric population.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Humanos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Criança , Anticorpos Anticitoplasma de Neutrófilos/imunologia
2.
Ann Allergy Asthma Immunol ; 130(6): 718-726, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36801438

RESUMO

Biologic immunomodulatory medications have rapidly expanded in the previous decades, providing new treatment options for individuals with a spectrum of oncologic, allergic, rheumatologic, and neurologic conditions. Biologic therapies alter immune function and can impair key host defense mechanisms, resulting in secondary immunodeficiency and increased infectious risks. Biologic medications can increase general risk for upper respiratory tract infections but can also be associated with unique infectious risks owing to distinct mechanisms of action. With the widespread use of these medications, providers in every area of medicine will likely care for individuals receiving biologic therapies and understanding their potential infectious complications can help mitigate these risks. This practical review discusses the infectious implications of biologics by class of medication and provides recommendations regarding the examination and screening both before therapy initiation and while the patient is receiving the medication. With this knowledge and background, providers can reduce risk whereas patients receive the treatment benefits of these biologic medications.


Assuntos
Produtos Biológicos , Hipersensibilidade , Infecções , Infecções Respiratórias , Humanos , Infecções/etiologia , Hipersensibilidade/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Imunomodulação , Produtos Biológicos/efeitos adversos
3.
Curr Allergy Asthma Rep ; 23(6): 341-350, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37171672

RESUMO

PURPOSE OF REVIEW: Since it first appeared, multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been compared to Kawasaki disease (KD). Although there were early parallels between MIS-C and KD, key differences emerged over time. Here, we aim to compare the pathogenesis, clinical presentation, treatment, and outcomes of MIS-C and KD. RECENT FINDINGS: In this article, we review and compare MIS-C and KD, highlighting differentiating features. We discuss the epidemiological and immunological factors along with clinical and laboratory features which discern MIS-C from KD. We also compare treatment and our understanding of long-term outcomes. Though parallels exist between MIS-C and KD, distinguishing the two is important for clinical management of patients, counseling about natural history, and determining long-term monitoring. While both MIS-C and KD are characterized by profound inflammation and inflammatory vasculopathy, further study is needed to determine whether they are distinct immunopathogenic disorders.


Assuntos
COVID-19 , Síndrome de Linfonodos Mucocutâneos , Humanos , Criança , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/terapia , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/terapia , Inflamação
4.
J Am Soc Nephrol ; 33(8): 1517-1527, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35672132

RESUMO

BACKGROUND: PR3-ANCA vasculitis has a genetic association with HLA-DPB1. We explored immunologic and clinical features related to the interaction of HLA-DPB1*04:01 with a strongly binding PR3 peptide epitope (PR3225-239). METHODS: Patients with ANCA vasculitis with active disease and disease in remission were followed longitudinally. Peripheral blood mononuclear cells from patients and healthy controls with HLA-DPB1*04:01 were tested for HLA-DPB1*04:01 expression and interaction with a PR3 peptide identified via in silico and in vitro assays. Tetramers (HLA/peptide multimers) identified autoreactive T cells in vitro. RESULTS: The HLA-DPB1*04:01 genotype was associated with risk of relapse in PR3-ANCA (HR for relapse 2.06; 95% CI, 1.01 to 4.20) but not in myeloperoxidase (MPO)-ANCA or the combined cohort. In silico predictions of HLA and PR3 peptide interactions demonstrated strong affinity between ATRLFPDFFTRVALY (PR3225-239) and HLA-DPB1*04:01 that was confirmed by in vitro competitive binding studies. The interaction was tested in ex vivo flow cytometry studies of labeled peptide and HLA-DPB1*04:01-expressing cells. We demonstrated PR3225-239 specific autoreactive T cells using synthetic HLA multimers (tetramers). Patients in long-term remission off therapy had autoantigenic peptide and HLA interaction comparable to that of healthy volunteers. CONCLUSIONS: The risk allele HLA-DPB1*04:01 has been associated with PR3-ANCA, but its immunopathologic role was unclear. These studies demonstrate that HLA-DPB1*04:01 and PR3225-239 initiate an immune response. Autoreactive T cells specifically recognized PR3225-239 presented by HLA-DPB1*04:01. Although larger studies should validate these findings, the pathobiology may explain the observed increased risk of relapse in our cohort. Moreover, lack of HLA and autoantigen interaction observed during long-term remission signals immunologic nonresponsiveness.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Vasculite , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Anticorpos Anticitoplasma de Neutrófilos , Autoantígenos , Cadeias beta de HLA-DP , Humanos , Leucócitos Mononucleares/metabolismo , Mieloblastina/genética , Peroxidase , Recidiva
5.
J Pediatr Hematol Oncol ; 43(8): 281-287, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34054047

RESUMO

Activated PI3 kinase delta syndrome (APDS) is a combined immunodeficiency characterized by recurrent sinopulmonary infections, increased risk of herpesvirus infections, lymphoproliferation, autoimmunity, and increased risk of lymphoid malignancies. Gain-of-function mutations in PIK3CD and PIK3R1 result in increased phosphoinositide-3-kinase-delta activity which causes hyperactivation of lymphocytes and abnormal development and activation of T and B cells. Cytopenias are the most common autoimmune process occurring in patients with APDS and typically occur as a later manifestation of the disease. Here we present a female patient with an early autoimmune hemolytic anemia, hepatosplenomegaly, and frequent infections presenting in infancy, followed by development of significant lymphadenopathy before her diagnosis with APDS type 1. She had significant improvement in her infectious history with immunoglobulin replacement, and control of autoimmune hemolytic anemia with initiation of sirolimus after her diagnosis with APDS type 1. We utilize this case to review the literature on APDS and present the novel finding of early-onset autoimmune disease in the setting of APDS. Autoimmune cytopenias are seen in many primary immunodeficiencies, and workup of autoimmune cytopenias in young patients should include evaluation for underlying immune disorder.


Assuntos
Anemia Hemolítica Autoimune/patologia , Doenças da Imunodeficiência Primária/complicações , Adulto , Anemia Hemolítica Autoimune/etiologia , Classe I de Fosfatidilinositol 3-Quinases , Feminino , Humanos , Prognóstico , Adulto Jovem
6.
Curr Cardiol Rep ; 23(11): 168, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599465

RESUMO

PURPOSE OF REVIEW: To review the spectrum of cardiac manifestations and treatments of multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19). RECENT FINDINGS: Studies demonstrate that up to 80% of children with MIS-C may have cardiac involvement on a spectrum of severity. Cardiac manifestations include myocarditis, coronary artery aneurysms, conduction abnormalities, and arrhythmias. Current treatments, including inotropic support, immunomodulatory therapy, and anti-coagulation, have been effective at resolving these cardiac findings in the majority of patients. COVID-19 can also cause myocarditis in the acute stage of illness and recent descriptions of COVID-19 vaccine myocarditis have occurred. Cardiac manifestations are common in MIS-C and should be assessed for at presentation and during the clinical course as indicated.


Assuntos
COVID-19 , Vacinas contra COVID-19 , Humanos , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica
7.
Kidney Int ; 98(3): 744-757, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32446935

RESUMO

ANCA vasculitis is an autoimmune disease with increased expression of the autoantigen genes, myeloperoxidase (MPO) and proteinase 3 (PRTN3), but the origin and significance of expression is less distinct. To clarify this, we measured MPO and PRTN3 messenger RNA in monocytes, normal-density neutrophils, and in enriched leukocytes from peripheral blood mononuclear cells. Increased autoantigen gene expression was detected in normal-density neutrophils and enriched leukocytes from patients during active disease compared to healthy individuals, with the largest difference in enriched leukocytes. RNA-seq of enriched leukocytes comparing active-remission pairs identified a gene signature for low-density neutrophils. Cell sorting revealed low-density neutrophils contained mature and immature neutrophils depending on the presence or absence of CD10. Both populations contributed to autoantigen expression but the frequency of immature cells in low-density neutrophils did not correlate with low-density neutrophil MPO or PRTN3 expression. Low-density neutrophils were refractory to MPO-ANCA induced oxidative burst, suggesting an alternative role for low-density neutrophils in ANCA vasculitis pathogenesis. In contrast, normal-density neutrophils were activated by MPO-ANCA and monoclonal anti-PR3 antibody. Normal-density neutrophil activation correlated with MPO and PRTN3 mRNA. Increased autoantigen gene expression originating from the mature low-density and normal-density neutrophils suggests transcriptional dysregulation is a hallmark of ANCA vasculitis. Thus, the correlation between autoantigen gene expression and antibody-mediated normal-density neutrophil activation connects autoantigen gene expression with disease pathogenesis.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos , Neutrófilos , Autoantígenos/genética , Expressão Gênica , Humanos , Leucócitos Mononucleares , Mieloblastina , Ativação de Neutrófilo , Peroxidase/genética
8.
Curr Allergy Asthma Rep ; 19(6): 32, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31089823

RESUMO

PURPOSE OF REVIEW: Sweet's syndrome (SS) is classically considered a hypersensitivity reaction often associated with autoimmune disorders and malignancy. SS has also been increasingly reported to occur with immunodeficiencies. We present a case of treatment-refractory, systemic SS as the initial manifestation in a young child with common variable immunodeficiency (CVID). We also review current literature about SS and concurrent immunodeficiencies and autoimmunity in CVID patients. RECENT FINDINGS: Few case reports exist regarding the co-occurrence of Sweet's syndrome and primary immunodeficiencies. SS is characterized by a pro-inflammatory state with a neutrophil predominance resulting in a spectrum of clinical manifestations. CVID is a multifactorial antibody deficiency that can be associated with autoimmunity, which some studies have proposed to be secondary to altered CD21 expression. SS occurring in patients with CVID has been infrequently reported, and one case study demonstrated improvement of Sweet's associated skin lesions with immunoglobulin replacement. In our case, the patient had multi-system SS refractory to multiple immunomodulatory therapies. To our knowledge, this is the first report of the effective and safe use of intravenous tocilizumab and oral lenalidomide to treat SS in a child with CVID. Immunoglobulin replacement reduced the frequency of infections and may have contributed to the opportunity to wean the immunosuppressive therapies for Sweet's syndrome. Sweet's syndrome as an initial manifestation of co-occurring immunodeficiencies is rare, and providers need a high index of suspicion. In addition, treatment of SS associated with an immunodeficiency can be a challenge. Treatment with immunoglobulin replacement reduces the frequency of infections, and in some patients with concurrent SS may improve skin lesions and reduce the need for immunomodulator therapy. Further study is necessary to better understand the pathogenesis of CVID in patients with SS and to identify possible biomarkers that predict who with SS are at risk for developing hypogammaglobulinemia.


Assuntos
Imunodeficiência de Variável Comum/epidemiologia , Síndrome de Sweet/epidemiologia , Criança , Humanos , Masculino
9.
Curr Allergy Asthma Rep ; 18(3): 14, 2018 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-29470661

RESUMO

PURPOSE OF REVIEW: Granulomatous-lymphocytic interstitial lung disease (GLILD) has classically been associated with common variable immune deficiency (CVID), but is increasingly being reported in other immunodeficiencies. We describe the second reported case of GLILD in a patient with 22q11.2 deletion syndrome (22q11.2DS) and review the recent literature surrounding GLILD. RECENT FINDINGS: GLILD is characterized by granulomata and lymphoproliferation. Consensus statements and retrospective and case-control studies have better elucidated the clinicopathological and radiographic manifestations of GLILD, allowing for its differentiation from similar conditions like sarcoidosis. Gaps of knowledge remain, however, particularly regarding optimal management strategies. Combination therapies targeting T and B cell populations have recently shown favorable results. GLILD is associated with poorer outcomes in CVID. Its recognition as a rare complication of 22q11.2DS and other immunodeficiencies therefore has important therapeutic and prognostic implications. Additional research is needed to better understand the natural history and pathogenesis of GLILD and to develop evidence-based practice guidelines.


Assuntos
Imunodeficiência de Variável Comum/complicações , Síndrome de DiGeorge/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Adolescente , Imunodeficiência de Variável Comum/patologia , Síndrome de DiGeorge/patologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/patologia , Masculino , Estudos Retrospectivos
10.
Pediatr Dermatol ; 35(5): e257-e261, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29656404

RESUMO

Pyoderma gangrenosum is a neutrophilic dermatosis that is rare in infancy, with only 20 cases reported in the literature. We present a case of infantile pyoderma gangrenosum refractory to topical steroids, tacrolimus, and dapsone as well as systemic steroids and infliximab that is currently well controlled with the addition of oral tacrolimus. To our knowledge, this is the first report of the effective, safe use of oral tacrolimus in combination with infliximab for infantile pyoderma gangrenosum. We review all current cases of infantile pyoderma gangrenosum, as well as tacrolimus and its role in the treatment of this condition.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Imunossupressores/uso terapêutico , Infliximab/uso terapêutico , Pioderma Gangrenoso/tratamento farmacológico , Tacrolimo/uso terapêutico , Feminino , Humanos , Lactente
12.
Curr Allergy Asthma Rep ; 16(8): 55, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27401913

RESUMO

Immune gamma globulin (IgG) has a long history in the treatment of both primary immune deficiency and autoimmune disorders. Disease indications continue to expand and new-generation products increase the versatility of delivery. This review encompasses a historical perspective as well as current and future implications of human immune globulin for the treatment of immune-mediated illness.


Assuntos
Autoimunidade/imunologia , Síndromes de Imunodeficiência/tratamento farmacológico , gama-Globulinas/uso terapêutico , Humanos , Síndromes de Imunodeficiência/imunologia
13.
Pediatr Radiol ; 46(12): 1630-1644, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27655432

RESUMO

Primary immunodeficiencies are a group of genetically determined disorders with diverse presentations. The purpose of this review is to provide a practical and brief description of a select number of these diseases and to discuss the important role the radiologist can have in making an early diagnosis and in detecting and following disease complications. The role of diagnostic imaging and informed performance and interpretation are vital in the diagnosis, surveillance and management of all primary immunodeficiency disorders.


Assuntos
Diagnóstico por Imagem/métodos , Síndromes de Imunodeficiência/diagnóstico por imagem , Adolescente , Criança , Pré-Escolar , Humanos , Lactente
15.
Curr Allergy Asthma Rep ; 14(7): 448, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24816552

RESUMO

The complement system is a major, multifunctional part of innate immunity and serves as a bridge between the innate and adaptive immune systems. It consists of more than 30 distinct proteins that interact with one another in a specific sequence. There are three pathways of complement activation: the classical, the lectin, and the alternative pathways. The three pathways are initiated by distinct mechanisms, but they all generate the same core set of effector molecules. Inherited complete deficiencies in complement components are generally very rare and predispose to infections and autoimmune disease. One of the better described associations is between deficiencies in early classical pathway components and the development of systemic lupus erythematosus. The goal of this review will be to discuss the associations between and the causal mechanisms of complement deficiencies and systemic lupus erythematosus.


Assuntos
Proteínas do Sistema Complemento/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Autoimunidade , Ativação do Complemento/imunologia , Proteínas do Sistema Complemento/deficiência , Citocinas/imunologia , Humanos , Tolerância Imunológica , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/terapia
16.
Artigo em Inglês | MEDLINE | ID: mdl-39275806

RESUMO

INTRODUCTION: Complement was long thought not to be involved in ANCA vasculitis pathogenesis until studies in murine models demonstrated its central role. The current theory is ANCA-activated neutrophils degranulate and release factors that activate complement, which, in turn, recruits more neutrophils and causes an inflammatory amplification loop that results in the vascular inflammation characteristic of disease. Targeting this amplification loop through complement inhibition has proven to be effective in ANCA vasculitis treatment. AREAS COVERED: A PubMed search was conducted using key terms 'ANCA vasculitis' AND 'complement system.' We review findings from experimental mouse models, in vitro studies, and human ANCA vasculitis that support a role for complement activation in disease pathogenesis. We also summarize results from pivotal clinical studies demonstrating the safety and efficacy of complement inhibition in ANCA vasculitis treatment. EXPERT OPINION: While complement activation is undoubtedly involved in ANCA vasculitis pathogenesis, less clear is whether measuring complement activation markers can reliably assess disease activity, predict those who will benefit from complement-targeting therapy, or identify patients in stable remission and able to stop therapy. Better understanding the clinical implications of complement activation will shed more light on the utility of complement inhibition and facilitate precision medicine in ANCA vasculitis.

17.
Front Nephrol ; 4: 1404451, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39015144

RESUMO

The role of stressors, insect bites, and infections on disease relapse of ANCA vasculitis has yet to be entirely explored, with limited retrospective studies focused on disease onset from small participant cohorts. Our study analyzes longitudinal survey data from 2011-2022 to evaluate this perspective from a large ANCA vasculitis cohort. We collected surveys every three to six months to obtain information on self-reported psychological stressors and significant life events, insect bites, and infections throughout clinical disease. We defined cohorts as those who relapsed (Relapse Cohort) and controls as those who did not relapse (Remission Cohort) during the study period. Survey responses were retrospectively reviewed during a 15-month timeframe prior to relapse or during 15 months of remission and categorized by type of stress event, insect bite, and infections at every available 3-month interval. There were no significant differences in stress and insect bites between the relapse and remission cohorts. Patients who relapsed reported more frequent upper respiratory infections and other infections, such as those affecting the skin and eyes, but there were no significant differences in the incidence of pulmonary or urinary infections compared to the remission cohort. There was a significant difference in reported upper respiratory infections 9 to 15 months prior to the relapse date, indicating a remote history of infections as a potentially significant physical stressor that may contribute to disease relapse. More frequent patient-reported infections, specifically upper respiratory infections, may contribute to patient vulnerability to relapse. Counseling and close monitoring of patients after infectious symptoms could aid in earlier detection of disease flares. Future studies are essential to further understand the importance of distal risk factors and how they impact relapse.

18.
Arthritis Rheumatol ; 76(3): 469-478, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37800549

RESUMO

OBJECTIVE: We compared clinical characteristics and renal response in patients with childhood-onset proliferative lupus nephritis (LN) treated with the EuroLupus versus National Institutes of Health (NIH) cyclophosphamide (CYC) regimen. METHODS: A retrospective cohort study was conducted at 11 pediatric centers in North America that reported using both CYC regimens. Data were extracted from the electronic medical record at baseline and 3, 6, and 12 months after treatment initiation with CYC. To evaluate the adjusted association between CYC regimen (EuroLupus vs NIH) and renal response over time, generalized estimating equations with a logit link were used. An interaction between time and CYC regimen was included, and a contrast between CYC regimens at 12 months was used to evaluate the primary outcome. RESULTS: One hundred forty-five patients (58 EuroLupus, 87 NIH) were included. EuroLupus patients were on average older at the start of current CYC therapy, had longer disease duration, and more commonly had relapsed or refractory LN compared with the NIH group. After multivariable adjustment, there was no significant association between CYC regimen and achieving complete renal response at 12 months (odds ratio [OR] of response for the EuroLupus regimen, reference NIH regimen: 0.76; 95% confidence interval [CI] 0.29-1.98). There was also no significant association between CYC regimen and achieving at least a partial renal response at 12 months (OR 1.35, 95% CI 0.57-3.19). CONCLUSION: Our study failed to demonstrate a benefit of the NIH regimen over the EuroLupus CYC regimen in childhood-onset proliferative LN. However, future prospective outcome studies are needed.


Assuntos
Nefrite Lúpica , Estados Unidos , Criança , Humanos , Nefrite Lúpica/tratamento farmacológico , Imunossupressores , Estudos Retrospectivos , Ciclofosfamida/uso terapêutico , Rim
19.
J Clin Trials ; 14(4)2024.
Artigo em Inglês | MEDLINE | ID: mdl-39035447

RESUMO

Background: The safety and efficacy of mycophenolate mofetil (MMF) for lupus nephritis (LN) treatment is established in adults and in some children. MMF is rapidly converted to the biologically active metabolite mycophenolic acid (MPA) whose pharmacokinetics (PK) is characterized by large inter- and intra-individual variability. Methods/Design: This randomized, double-blind, active comparator, controlled clinical trial of pediatric subjects with proliferative LN compares pharmacokinetically-guided precision-dosing of MMF (MMFPK, i.e. the dose is adjusted to the target area under the concentration-time curve (AUC0-12h) of MPA ≥ 60-70 mg*h/L) and MMF dosed per body surface area (MMFBSA, i.e. MMF dosed 600 mg/m2 body surface area), with MMF dosage taken about 12 hours apart. At baseline, subjects are randomized 1:1 to receive blinded treatment with MMFPK or MMFBSA for up to 53 weeks. The primary outcome is partial clinical remission of LN (partial renal response, PRR) at week 26, and the major secondary outcome is complete renal response (CRR) at week 26. Subjects in the MMFBSA arm with PRR at week 26 will receive MMFPK from week 26 onwards, while subjects with CRR will continue MMFBSA or MMFPK treatment until week 53. Subjects who achieve PRR at week 26 are discontinued from study intervention. Discussion: The Pediatric Lupus Nephritis Mycophenolate Mofetil (PLUMM) study will provide a thorough evaluation of the PK of MMF in pediatric LN patients, yielding a head-to-head comparison of MMFBSA and MMFPK for both safety and efficacy. This study has the potential to change current treatment recommendations for pediatric LN, thereby significantly impacting childhood-onset SLE (cSLE) disease prognosis and current clinical practice.

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