Macrophage Activation Syndrome Research Articles

Predictors of disease course in systemic juvenile idiopathic arthritis.

To identify potential predictors of the disease course of systemic juvenile idiopathic arthritis (sJIA) at the time of diagnosis. This retrospective observational study was conducted in patients diagnosed with sJIA in our hospital between April 2009 and October 2023. The relationship between the disease course of sJIA patients and demographic, clinical, laboratory findings and complications were analyzed. Of the 51 patients diagnosed with sJIA, 26 (51%) patients had monocyclic, 7 (13.7%) polycyclic and 18 (35.2%) persistent disease course. 3 (5.8%) patients had a persistent disease course with persistent arthritis developed flares with systemic manifestations during follow-up. The presence of arthritis, polyarticular involvement, and hip involvement at the time of diagnosis were associated with persistent disease course (p=0.009, p=0.003, p=0.003). Serositis and higher white blood cell and neutrophil counts at the time of diagnosis were associated with a monocyclic disease course (p=0.034, p=0.002, p=0.008). However, no significant correlation was found between macrophage activation syndrome (MAS) and disease course (p=1). Systemic JIA patients with polyarthritis and hip involvement at disease onset may develop a persistent course. Although MAS is an important complication of sJIA, its effect on the course of the disease was not found in this study.

A MASsive attack: a pediatric case of macrophage activation syndrome complicated by DIC as an onset of systemic juvenile idiopathic arthritis successfully treated with anakinra and review of the literature.

Macrophage activation syndrome (MAS) is one of the most severe complications of systemic juvenile idiopathic arthritis (sJIA). Around 10% of patients with sJIA exhibit systemic symptoms accompanied by macrophage activation syndrome (MAS), but it may occur subclinically in another 30-40%. In this article, we present a case of a 3-year-old girl diagnosed with sever MAS as an onset of sJIA complicated by disseminated intravascular coagulation (DIC). First symptoms of sJIA were observed about 5months before setting the diagnose, and it was resembling urticaria. A comprehensive allergological diagnostics were conducted, but no cause for the skin changes was identified. A few weeks before admission to the hospital, the girl was presented with a high fever. During the hospital stay, viral, bacterial, and fungal infections were ruled out. However, the findings indicated significantly elevated markers of inflammation (ferritin, CRP, ESR) in the conducted tests. Meanwhile, swelling of the feet and ankle joints was also observed. Based on Ravelli criteria, we set the diagnosis of MAS in a course of sJIA. We implemented treatment with steroid pulses, followed by cyclosporine; however, her clinical condition did not improve. Despite intensive treatment, skin petechiae were observed twice, and laboratory tests revealed a very high INR along with an extremely low level of fibrinogen. The patient required multiple plasma transfusions and clotting factor administrations. Due to the severe condition of the girl, we initiated biological treatment with anakinra, after which the child's condition gradually improved. In this case, we want to present how dynamic and life-threatening the course of MAS can be. In the discussion, we are also comparing our approach and the applied treatment with the currently available knowledge.

Efficacy and safety of canakinumab in systemic juvenile idiopathic arthritis, the first Chinese experience

BackgroundSystemic juvenile idiopathic arthritis (sJIA) is a severe form of juvenile arthritis that is characterized by chronic joint inflammation and systemic symptoms such as fever, rash, and organ involvement. Anti-IL-6 receptor monoclonal antibody tocilizumab is an effective treatment. However, some patients still experience persisting or recurrent symptoms and the real-world effectiveness of canakinumab in Chinese patients with sJIA has never been reported. Therefore, this study aimed to assess the efficacy and safety of canakinumab in Chinese patients with sJIA using real-world data.MethodsWe conducted a retrospective study on children with active sJIA. Clinical features, laboratory data, corticosteroid dosage, and adverse events (AEs) were collected at baseline and at 4, 8, 12, and 24 weeks after initiating canakinumab treatment.ResultsSeven female and four male patients were included in the study. All patients had previously been treated with tocilizumab and were administered canakinumab for 12.4 ± 3.4 months. Notably, significant improvements were observed in both clinical signs and symptoms as well as laboratory indicators. Four children under corticosteroid treatment were able to successfully discontinue their corticosteroid therapy: one at week 4, two at week 12, and one at week 24. Notably, there was a significant reduction in the number of tender and swollen joints (P = 0.0059) as well as the systemic juvenile arthritis disease activity score (P < 0.0001). The most common AE was infection, but no patients experienced serious AEs. No cases of macrophage activation syndrome or death were reported during the follow-up period.ConclusionsCanakinumab was found to be potentially efficacious and safe in Chinese patients with sJIA. No new AEs were observed with canakinumab treatment.

The systemic score may identify life-threatening evolution in Still's disease: data from the GIRRCS AOSD-study group and the AIDA Network Still's Disease Registry.

To evaluate the clinical usefulness of the systemic score in the prediction of life-threatening evolution in Still's disease. To assess the clinical relevance of each component of the systemic score in predicting life-threatening evolution and to derive patient subsets accordingly. A multicenter, observational, prospective study was designed including patients included in the GIRRCS (Gruppo Italiano Di Ricerca in Reumatologia Clinica e Sperimentale) AOSD-study group and AIDA (AutoInflammatory Disease Alliance) Network Still's Disease Registry. Patients were assessed if variables to derive the systemic score were available. The life-threatening evolution was defined as mortality, whichever the clinical course, and/or macrophage activation syndrome (MAS), a secondary hemophagocytic lymphohistiocytosis associated with a poor prognosis. Totally 597 patients with Still's disease were assessed (age 36.6±17.3 years; male 44.4%). The systemic score, assessed as continuous variable, significantly predicted the life-threatening evolution (OR: 1.24, 95%CI:1.07-1.42; p=0.004). A systemic score ≥7 also significantly predicted the likelihood of a patient experiencing life-threatening evolution (OR: 3.36, 95%CI:1.81-6.25; p<0.001). Assessing the clinical relevance of each component of the systemic score, liver involvement (OR: 1.68, 95%CI:1.48-2.67; p=0.031) and lung disease (OR: 2.12, 95%CI:1.14-4.49; p=0.042) both significantly predicted life-threatening evolution. The clinical characteristics of patients with liver involvement and lung disease were derived, highlighting their relevance in multiorgan disease manifestations. The clinical utility of the systemic score was shown in identifying Still's disease at higher risk of life-threatening evolution in a large cohort. Furthermore, the clinical relevance of liver involvement and lung disease was highlighted.

Identification of miRNAs that target Fcγ receptor-mediated phagocytosis during macrophage activation syndrome.

Macrophage activation syndrome (MAS) is a life-threatening complication of systemic juvenile arthritis, accompanied by cytokine storm and hemophagocytosis. In addition, COVID-19-related hyperinflammation shares clinical features of MAS. Mechanisms that activate macrophages in MAS remain unclear. Here, we identify the role of miRNA in increased phagocytosis and interleukin-12 (IL-12) production by macrophages in a murine model of MAS. MAS significantly increased F4/80+ macrophages and phagocytosis in the mouse liver. Gene expression profile revealed the induction of Fcγ receptor-mediated phagocytosis (FGRP) and IL-12 production in the liver. Phagocytosis pathways such as High-affinity IgE receptor is known as Fc epsilon RI -signaling and pattern recognition receptors involved in the recognition of bacteria and viruses and phagosome formation were also significantly upregulated. In MAS, miR-136-5p and miR-501-3p targeted and caused increased expression of Fcgr3, Fcgr4, and Fcgr1 genes in FGRP pathway and consequent increase in phagocytosis by macrophages, whereas miR-129-1-3p and miR-150-3p targeted and induced Il-12. Transcriptome analysis of patients with MAS revealed the upregulation of FGRP and FCGR gene expression. A target analysis of gene expression data from a patient with MAS discovered that miR-136-5p targets FCGR2A and FCGR3A/3B, the human orthologs of mouse Fcgr3 and Fcgr4, and miR-501-3p targets FCGR1A, the human ortholog of mouse Fcgr1. Together, we demonstrate the novel role of miRNAs during MAS pathogenesis, thereby suggesting miRNA mimic-based therapy to control the hyperactivation of macrophages in patients with MAS as well as use overexpression of FCGR genes as a marker for MAS classification.

Systemic juvenile idiopathic arthritis-associated lung disease: A retrospective cohort study.

Lung damage in systemic juvenile arthritis (sJIA) is one of the contemporary topics in pediatric rheumatology. Several previous studies showed the severe course and fatal outcomes in some patients. The information about interstitial lung disease (ILD) in the sJIA is scarce and limited to a total of 100 cases. To describe the features of sJIA patients with ILD in detail. In the present retrospective cohort study, information about 5 patients less than 18-years-old with sJIA and ILD were included. The diagnosis of sJIA was made according to the current 2004 and new provisional International League of Associations for Rheumatology criteria 2019. ILD was diagnosed with chest computed tomography with the exclusion of other possible reasons for concurrent lung involvement. Macrophage activation syndrome (MAS) was diagnosed with HLH-2004 and 2016 EULAR/ACR/PRINTO Classification Criteria and hScores were calculated during the lung involvement. The onset age of sJIA ranged from 1 year to 10 years. The time interval before ILD ranged from 1 mo to 3 years. The disease course was characterized by the prevalence of the systemic features above articular involvement, intensive rash (100%), persistent and very active MAS (hScore range: 194-220) with transaminitis (100%), and respiratory symptoms (100%). Only 3 patients (60%) developed a clubbing phenomenon. All patients (100%) had pleural effusion and 4 patients (80%) had pericardial effusion at the disease onset. Two patients (40%) developed pulmonary arterial hypertension. Infusion-related reactions to tocilizumab were observed in 3 (60%) of the patients. One patient with trisomy 21 had a fatal disease course. Half of the remaining patients had sJIA remission and 2 patients had improvement. Lung disease improved in 3 patients (75%), but 1 of them had initial deterioration of lung involvement. One patient who has not achieved the sJIA remission had the progressed course of ILD. No cases of hyper-eosinophilia were noted. Four patients (80%) received canakinumab and one (20%) tocilizumab at the last follow-up visit. ILD is a severe life-threatening complication of sJIA that may affect children of different ages with different time intervals since the disease onset. Extensive rash, serositis (especially pleuritis), full-blown MAS with transaminitis, lymphopenia, trisomy 21, eosinophilia, and biologic infusion reaction are the main predictors of ILD. The following studies are needed to find the predictors, pathogenesis, and treatment options, for preventing and treating the ILD in sJIA patients.

α2-antiplasmin is associated with macrophage activation and fibrin in a macrophage activation syndrome mouse model.

Macrophage activation syndrome (MAS) is a life-threatening condition, characterized by cytopenia, multi-organ dysfunction, and coagulopathy associated with excessive activation of macrophages. In this study, we investigated that the roles of α2-antiplasmin (α2AP) in the progression of MAS using fulminant MAS mouse model induced by Toll-like receptor-9 (TLR-9) agonist (CpG) and d-galactosamine (DG). α2AP deficiency attenuated macrophage accumulation, liver injury, and fibrin deposition in the MAS model mice. Interferon-γ (IFN-γ) is associated with macrophage activation, including migration, and plays a pivotal role in MAS progression. α2AP enhanced the IFN-γ-induced migration, and tissue factor (TF) production. Additionally, we showed that fibrin induced macrophage activation and tumor necrosis factor-α (TNF-α) production. Moreover, the blockade of α2AP by neutralizing antibodies attenuated macrophage accumulation, liver injury, and fibrin deposition in the MAS model mice. These data suggest that α2AP may regulate IFN-γ-induced responses and be associated with macrophage activation and fibrin deposition in the MAS progression.

Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis on anti-interleukin-1 or -6 therapy.

The aim of this study is to investigate the effect of anti-interleukin (IL)-1/-6 biologics on systemic juvenile idiopathic arthritis (sJIA)-associated macrophage activation syndrome (MAS). Demographic, clinical, and laboratory data of patients followed up with a diagnosis of sJIA-associated MAS assessed from sixteen pediatric rheumatology centers across the country. The clinical and laboratory features of MAS developing while on biological drugs were compared with those without this treatment. One hundred and sixty-two patients were included in the study. 45 of the MAS events were detected under the effect of anti-IL-1/-6 biologics, while the patients experiencing the remaining 155 events have not received biological treatment in the last three months. Platelet count [128 (72-232) vs 199 (130-371) 109/l], ferritin level on admission [1107 (676-2050) vs 2863 (1193-9562) ng/ml], C-reactive protein level [15.4 (2.9-56) vs 90 (32-160) mg/l], erythrocyte sedimentation rate [13 (3-36) vs 43.5 (13-77) mm/h] and fever duration [5 (4-7.5) vs 10 (7-14.3) days] were found lower in the group under the impact of anti-IL-1/-6 biologics. Among patients treated with biologics, 26.6% did not meet the published 2016 MAS classification criteria at presentation. The rates of hepatomegaly and splenomegaly were relatively lower in the canakinumab-treated group when compared with those receiving other biologicals or to patients, not on biologicals. Anti-IL-1/-6 therapies can mask the clinical and laboratory features of MAS, and proposed guidelines for MAS classification criteria may not be met.

Subcutaneous anakinra in the management of refractory MIS-C in France.

Multisystemic inflammatory syndrome in children (MIS-C) is a therapeutic emergency and can lead to myocardial dysfunction (17%-75%) and heart failure (52%-53%). Intravenous immunoglobulins (IVIG) and corticosteroids (CST) have been validated for the management of this condition. Recent reports suggest that an interleukin-1(IL-1) receptor antagonist, namely anakinra, may be a valuable add-on to the 2019 novel coronavirus disease (COVID-19) treatment for refractory patients. The purpose of this study was to describe the clinico-biological characteristics of patients treated with anakinra as well as the efficacy and safety of subcutaneous anakinra therapy in this condition. The prospective multicentre study of children hospitalized for MIS-C between March 2020 and September 2022, including 23 international paediatric centres, followed for a mean duration of 3.072 ± 3.508 months. The patient data were extracted from the Juvenile Inflammatory Rheumatism (JIR) cohort. The clinico-pathological characteristics, cardiac ultrasound data, and adverse events were reported in patients receiving anakinra. Of the 470 children admitted with MIS-C, 18 French patients (50% girls) with a mean age of 10.06 ± 3.9 years were treated with subcutaneous anakinra. Anakinra was used in two situations, macrophage activation syndrome (MAS) (4 patients) and heart failure (14 patients) with a median left ventricular ejection fraction (LVEF) of 39.5% (30%-45%). The average dose of anakinra received was 2.53 ± 1.3 mg/kg/day for a median duration of 3 days. Prior to introduction, 78% (n = 14/18) of the patients had received CST and 56% (n = 10/18) had received IVIG. Only two patients received IVIG alone and six received CST alone plus anakinra. In 10% of cases, IVIG was poorly tolerated from a cardiovascular point of view and was discontinued. Transient elevations in serum transaminases were noted in four patients on anakinra without the need for treatment or dose modification. In all patients, rapid (48 h) improvement in myocardial function was observed (LVEF > 55%) with a concomitant significant decrease in myocardial enzymes (p < 0.05). All patients survived with complete recovery of cardiac function without sequelae. Subcutaneous anakinra appears to be a safe and effective treatment for the management of heart failure or MAS in MIS-C patients. The value of IVIG in these two situations remains to be reviewed.

Cardiac Involvement in Patients With Multisystem Inflammatory Syndrome in Adults.

Multisystemic inflammatory syndrome in adults is a hyperinflammatory condition following (within 4-12 weeks) SARS-CoV-2 infection. Here, the dysregulation of the immune system leads to a multiorgan involvement often affecting the heart. Cardiac involvement in multisystemic inflammatory syndrome in adults has been described mainly in young men without other comorbidities and may present with different clinical scenarios, including acute heart failure, life-threatening arrhythmias, pericarditis, and myocarditis, with a nonnegligible risk of mortality (up to 7% of all cases). The heterogeneity of its clinical features and the absence of a clear case definition make the differential diagnosis with other postinfectious (eg, infective myocarditis) and hyperinflammatory diseases (eg, adult Still disease and macrophage activation syndrome) challenging. Moreover, the evidence on the efficacy of specific treatments targeting the hyperinflammatory response underlying this clinical condition (eg, glucocorticoids, immunoglobulins, and other immunomodulatory agents) is sparse and not supported by randomized clinical trials. In this review article, we aim to provide an overview of the clinical features and the diagnostic workup of multisystemic inflammatory syndrome in adults with cardiac involvement, highlighting the possible pathogenetic mechanisms and the therapeutic management, along with remaining knowledge gaps in this field.

TEMPORARY REMOVAL: Mortalité maternelle de causes indirectes (hors AVC, maladies cardiovasculaires et infections) en France 2016–2018

Maternal deaths from indirect obstetric causes result from a pre-existing condition or a condition that occurred during pregnancy without obstetric causes but was aggravated by the physiological effects of pregnancy. Twenty-nine deaths with an indirect cause related to a pre-existing condition, excluding circulatory diseases or infections, were analysed by the expert committee. Pre-pregnancy pathology was documented in 16 women (epilepsy, n=7; amyloid angiopathy, n=1; Dandy Walker syndrome, n=1; autoimmune diseases, n=3; diffuse infiltrative pneumonitis, n=1; thrombotic thrombocytopenic purpura, n=1; ovarian cancer in fragile X, n=1; major sickle cell disease, n=1). In 13 women, the pathology was unknown before pregnancy (breast cancer, n=9, epilepsy diagnosed during pregnancy, n=1, brain tumours, n=2 meningioma type, macrophagic activation syndrome, n=1). Death was associated with neoplastic or tumour pathology in 13 women (45%). At the same time, epilepsy was responsible for the death of 8 women (27%), making it the most common cause of death. For both neoplasia and epilepsy, about 50% of deaths were preventable, mainly due to undiagnosed and/or delayed treatment in the case of cancer and failure to monitor or adjust treatment in the case of epilepsy. Pre-conception counselling is therefore strongly recommended if a woman has a known chronic medical condition prior to pregnancy. Finally, if there is a family history of breast cancer, a breast examination is strongly recommended from the first visit during pregnancy, and any breast lumps should be investigated as soon as possible to avoid delaying appropriate treatment.

136 - The intersection between hematology-oncology and rheumatology: hemophagocytic lymphohistiocytosis and macrophage activation syndrome in the setting of neutropenic fever

136 - The intersection between hematology-oncology and rheumatology: hemophagocytic lymphohistiocytosis and macrophage activation syndrome in the setting of neutropenic fever

Macrophage activation syndrome: a review of recent renal findings

The pathogenesis of Macrophage activation syndrome consists of excessive macrophage and T-cell activation, leading to the uncontrolled release of cytokines and chemokines, which can cause multi-organ dysfunction. The diagnostic criteria for MAS include fever, splenomegaly, cytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis, low or absent natural killer cell activity, elevated ferritin levels, and elevated soluble interleukin-2 receptor levels. Kidney involvement in this disease included glomerular changes, including mesangial expansion, endocapillary proliferation, and thrombotic microangiopathy. Renal biopsy in MAS may also show evidence of macrophage infiltration and activation, such as the presence of hemophagocytic macrophages within the glomeruli and interstitium. These macrophages may contain phagocytosed erythrocytes, platelets, and other cells, indicating ongoing hemophagocytosis. The presence of hemophagocytic macrophages on renal biopsy is highly suggestive of MAS and can help differentiate it from other causes of acute kidney injury (AKI). Management of macrophage activation syndrome-associated kidney involvement involves treating the underlying autoimmune disorder and controlling the systemic inflammation. This may include the use of immunosuppressive medications, such as corticosteroids, disease-modifying anti-rheumatic drugs, and biological agents. Supportive measures, such as renal replacement therapy, may be necessary in severe cases of renal dysfunction.

[Hemophagocytic lymphohistiocytosis and macrophage activation syndrome : A multidisciplinary challenge].

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that is characterized by hyperferritinemia, cytopenia, disseminated intravascular coagulopathy and functional disorders of the liver and the central nervous system. The term macrophage activation syndrome is predominantly used for secondary HLH in the context of autoimmune diseases (e.g., systemic juvenile idiopathic arthritis). In addition, malignancies and genetic inborn errors of immunity can predispose to the development of HLH. Infections (e.g., Epstein-Barr virus) in turn represent possible triggers of an acute episode. Due to the unspecific manifestation of the disease, a systematic evaluation of the organ systems is recommended in the clinical and laboratory analytical clarification of hyperinflammatory syndromes. In general, the treatment should be carried out by a multidisciplinary team with expertise in rheumatology, hematological oncology, infectious diseases and intensive care medicine. The primary treatment of HLH usually consists of glucocorticoids and in cases of a rapid deterioration of the condition anakinra (interleukin 1 block) and intravenous immunoglobulins can be employed. Treatment of the underlying disease should be consequently carried out in parallel, together with antimicrobial treatment.

Children systemic lupus erythematosus-associated pancreatitis

ObjectiveTo early recognise and improve the prognosis of children systemic lupus erythematosus (cSLE)-associated pancreatitis by summarising and analysing clinical features and prognosis data from 12 cases.MethodsRetrospective analysis of clinical data from 12 cases of cSLE-associated pancreatitis diagnosed and treated from January 2016 to December 2021 at hospitals such as Children’s Hospital of Capital Institute of Paediatrics.ResultsThe median SLEDAI-2K score for disease activity was 18.00 (range 12.25–21.00) in the case group and 10.00 (range 7.00–18.00) in the control group, with a statistically significant difference (P < 0.05) between the two groups. The case group had a higher proportion of abdominal pain, vomiting, abdominal distension, pleural effusion, Raynaud’s phenomenon (RP), splenic infarction, and concurrent macrophage activation syndrome (MAS) than the control group, with a statistically significant difference (P < 0.05). Serum ferritin (SF), alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), amylase, and increased 24-h urine protein levels were statistically different between the two groups (P < 0.05); platelet counts (PLT) reduction was also statistically different (P < 0.05). The case group had a higher proportion of methylprednisolone pulse therapy, cyclophosphamide pulse therapy during remission induction, and therapeutic plasma exchange than the control group, with a statistically significant difference (P < 0.05) between the two.ConclusionCSLE-associated pancreatitis has a high fatality rate. The presence of RP, splenic infarction, pleural effusion, and MAS warrants attention from clinicians regarding the possibility of pancreatitis. Once pancreatitis is detected, the primary disease needs active treatment for better prognosis.

Recent advances and evolving concepts in Still's disease.

Still's disease is a rare inflammatory syndrome that encompasses systemic juvenile idiopathic arthritis and adult-onset Still's disease, both of which can exhibit life-threatening complications, including macrophage activation syndrome (MAS), a secondary form of haemophagocytic lymphohistiocytosis. Genetic insights into Still's disease involve both HLA and non-HLA susceptibility genes, suggesting the involvement of adaptive immune cell-mediated immunity. At the same time, phenotypic evidence indicates the involvement of autoinflammatory processes. Evidence also implicates the type I interferon signature, mechanistic target of rapamycin complex 1 signalling and ferritin in the pathogenesis of Still's disease and MAS. Pathological entities associated with Still's disease include lung disease that could be associated with biologic DMARDs and with the occurrence of MAS. Historically, monophasic, recurrent and persistent Still's disease courses were recognized. Newer proposals of alternative Still's disease clusters could enable better dissection of clinical heterogeneity on the basis of immune cell profiles that could represent diverse endotypes or phases of disease activity. Therapeutically, data on IL-1 and IL-6 antagonism and Janus kinase inhibition suggest the importance of early administration in Still's disease. Furthermore, there is evidence that patients who develop MAS can be treated with IFNγ antagonism. Despite these developments, unmet needs remain that can form the basis for the design of future studies leading to improvement of disease management.

Humanization with CD34-positive hematopoietic stem cells in NOG-EXL mice results in improved long-term survival and less severe myeloid cell hyperactivation phenotype relative to NSG-SGM3 mice.

NSG-SGM3 and NOG-EXL mice combine severe immunodeficiency with transgenic expression of human myeloid stimulatory cytokines, resulting in marked expansion of myeloid populations upon humanization with CD34+ hematopoietic stem cells (HSCs). Humanized NSG-SGM3 mice typically develop a lethal macrophage activation syndrome and mast cell hyperplasia that limit their use in long-term studies (e.g., humanization followed by tumor xenotransplantation). It is currently unclear to what extent humanized NOG-EXL mice suffer from the same condition observed in humanized NSG-SGM3 mice. We compared the effects of human CD34+ HSC engraftment in these two strains in an orthotopic patient-derived glioblastoma model. NSG-SGM3 mice humanized in-house were compared to NOG-EXL mice humanized in-house and commercially available humanized NOG-EXL mice. Mice were euthanized at humane or study endpoints, and complete pathological assessments were performed. A semiquantitative multiparametric clinicopathological scoring system was developed to characterize chimeric myeloid cell hyperactivation (MCH) syndrome. NSG-SGM3 mice were euthanized at 16 weeks after humanization because of severe deterioration of clinical conditions. Humanized NOG-EXL mice survived to the study endpoint at 22 weeks after humanization and showed less-severe MCH phenotypes than NSG-SGM3 mice. Major differences included the lack of mast cell expansion and limited tissue/organ involvement in NOG-EXL mice compared to NSG-SGM3 mice. Engraftment of human lymphocytes, assessed by immunohistochemistry, was similar in the two strains. The longer survival and decreased MCH phenotype severity in NOG-EXL mice enabled their use in a tumor xenotransplantation study. The NOG-EXL model is better suited than the NSG-SGM3 model for immuno-oncology studies requiring long-term survival after humanization.

SERUM FERRITIN AND SERUM LACTATE DEHYDROGENASE LEVELS AMONG COVID-19 PATIENTS

Objectives: The aim of this study was to estimate serum ferritin and serum lactate dehydrogenase (LDH) values among COVID-19-positive and COVID-19-negative subjects. Methods: The study was conducted on 152 cases; 76 were COVID-19 diseased, and 76 were COVID-19 free. Serum ferritin and serum LDH levels were estimated. Result: Average ferritin levels among COVID-19 diseased were 529.33 ng/ml compared to 450.92 ng/ml among negative individuals. Similarly, the LDH level among positive persons was 338.50 IU/L and 303.30 IU/L among hostile people. Conclusion: The uncontrolled and dysfunctional immune response is connected with macrophage activation and hyperferritinemic syndrome. Elevated LDH readings seem to reflect that multiple organ injury and failure may play a more prominent role in influencing the clinical outcomes in patients with COVID-19.

Macrophage Activation Syndrome Secondary to Histoplasmosis in an Adult Female Carrier of X-linked Chronic Granulomatous Disease with Extreme Lyonization.

not applicable to a Letter to the Editor.

Macrophage activation syndrome with acute hepatitis in a patient with adult-onset immunodeficiency with anti-interferon gamma antibodies: a case report

BackgroundMacrophage activation syndrome is a rare disorder leading to unregulated immune activity manifesting with nonspecific constitutional symptoms, laboratory abnormalities, and multiorgan involvement. We report the case of a patient who presented with acute hepatitis secondary to macrophage activation syndrome diagnosed by liver biopsy and successfully treated with intravenous immune globulin, anakinra, and rituximab.Case presentationA 42-year-old Laotian woman with adult-onset immunodeficiency with anti-interferon gamma antibodies presented with a fever, headache, generalized myalgia, dark urine, and reduced appetite in the setting of family members at home with similar symptoms. Her laboratory workup was notable for evidence of acute hepatitis without acute liver failure. After an unrevealing comprehensive infectious and noninvasive rheumatologic workup was completed, a liver biopsy was performed ultimately revealing the diagnosis of macrophage activation syndrome. She was successfully treated with intravenous immune globulin, anakinra, and rituximab.ConclusionThis case highlights the importance of maintaining macrophage activation syndrome on the differential of a patient with acute hepatitis of unknown etiology in the correct clinical context and the value of a liver biopsy in making a diagnosis when noninvasive testing is unrevealing.