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Article: Diagnosing Hemophagocytic Lymphohistiocytosis with Machine Learning: A Proof of Concept.

El Jammal, Thomas / Guerber, Arthur / Prodel, Martin / Fauter, Maxime / Sève, Pascal / Jamilloux, Yvan

2022 Volume 11, Issue 20

Abstract: Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome characterized by uncontrolled activation of immune cells and mediators. Two diagnostic tools are widely used in clinical practice: the HLH-2004 criteria and the Hscore. Despite their good ...

Abstract	Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome characterized by uncontrolled activation of immune cells and mediators. Two diagnostic tools are widely used in clinical practice: the HLH-2004 criteria and the Hscore. Despite their good diagnostic performance, these scores were constructed after a selection of variables based on expert consensus. We propose here a machine learning approach to build a classification model for HLH in a cohort of patients selected by glycosylated ferritin dosage in our tertiary center in Lyon, France. On a dataset of 207 adult patients with 26 variables, our model showed good overall diagnostic performances with a sensitivity of 71.4% and high specificity, and positive and negative predictive values which were 100%, 100%, and 96.9%, respectively. Although generalization is difficult on a selected population, this is the first study to date to provide a machine-learning model for HLH detection. Further studies will be required to improve the machine learning model performances with a large number of HLH cases and with appropriate controls.
Language	English
Publishing date	2022-10-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11206219
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Article ; Online: Uveitis in Giant Cell Arteritis: A Retrospective Study of Seven Observational Cases and Literature Review.

Gil, William / Kodjikian, Laurent / Andre, Marc / Kaur, Indeep / Durel, Cécile Audrey / Hot, Arnaud / Fauter, Maxime / Chaigne, Benjamin / Smets, Perrine / Samson, Maxime / Seve, Pascal

Ocular immunology and inflammation

2023 , Page(s) 1–8

Abstract: Purpose: To describe the demographic and clinical characteristics of uveitis in patients with giant cell arteritis (GCA), their treatments, and evolution.: Methods: A national retrospective cohort study was performed. The inclusion criteria were as ... ...

Abstract	Purpose: To describe the demographic and clinical characteristics of uveitis in patients with giant cell arteritis (GCA), their treatments, and evolution. Methods: A national retrospective cohort study was performed. The inclusion criteria were as follows: patients with GCA fulfilling the 2022 ACR/EULAR criteria and a diagnostic of uveitis attested by an ophthalmologist. Results: Seven women were included. The median age at diagnosis of uveitis was 71 years (64-84). All uveitis were diagnosed during active GCA (five at initial diagnosis, two at relapse). All uveitis were acute (100%), mostly anterior (86%) and bilateral (71%). Granulomatous features were less common (29%). All uveitis were treated with local and systemic corticosteroids. After a median follow-up of 30 (21-55) months, all patients achieved complete ophthalmic remission, with only one relapse at 2 years. GCA was also in complete remission. Conclusions: Uveitis could reveal GCA, and its presence correlated with disease activity of GCA. The most frequent clinical presentation of uveitis was acute and anterior; using local and systemic corticosteroids, the prognosis was favorable.
Language	English
Publishing date	2023-10-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1193873-0
ISSN	1744-5078 ; 0927-3948
ISSN (online)	1744-5078
ISSN	0927-3948
DOI	10.1080/09273948.2023.2264383
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Article: Extreme Hyperferritinemia: Causes and Prognosis.

Fauter, Maxime / Mainbourg, Sabine / El Jammal, Thomas / Guerber, Arthur / Zaepfel, Sabine / Henry, Thomas / Gerfaud-Valentin, Mathieu / Sève, Pascal / Jamilloux, Yvan

Journal of clinical medicine

2022 Volume 11, Issue 18

Abstract: The significance of extreme hyperferritinemia and its association with certain diagnoses and prognoses are not well characterized. We performed a retrospective analysis of adult patients with at least one total serum ferritin (TSF) measurement ≥ 5000 µg/ ... ...

Abstract	The significance of extreme hyperferritinemia and its association with certain diagnoses and prognoses are not well characterized. We performed a retrospective analysis of adult patients with at least one total serum ferritin (TSF) measurement ≥ 5000 µg/L over 2 years, in three university hospitals. Conditions associated with hyperferritinemia were collected, and patients were classified into 10 etiological groups. Intensive care unit (ICU) transfer and mortality rates were recorded. A total of 495 patients were identified, of which 56% had a TSF level between 5000 and 10,000 µg/L. There were multiple underlying causes in 81% of the patients. The most common causes were infections (38%), hemophagocytic lymphohistiocytosis (HLH, 18%), and acute hepatitis (14%). For TSF levels > 10,000 µg/L, there were no solid cancer or hematological malignancy without another cause of hyperferritinemia. Isolated iron-overload syndromes never exceeded TSF levels > 15,000 µg/L. Extreme hyperferritinemia (TSF levels > 25,000 µg/L) was associated with only four causes: HLH, infections, acute hepatitis and cytokine release syndromes. A total of 32% of patients were transferred to an ICU, and 28% died. Both ICU transfer rate and mortality were statistically associated with ferritin levels. An optimized threshold of 13,405 μg/L was the best predictor for the diagnosis of HLH, with a sensitivity of 76.4% and a specificity of 79.3%. Hyperferritinemia reflects a variety of conditions, but only four causes are associated with extreme hyperferritinemia, in which HLH and acute hepatitis are the most common. Extreme hyperferritinemia has a poor prognosis with increased mortality.
Language	English
Publishing date	2022-09-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11185438
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Article ; Online: Diagnostic value of elevated serum angiotensin-converting enzyme and lymphopenia in patients with granulomatous hepatitis.

El Jammal, Thomas / Dhelft, François / Pradat, Pierre / Bailly, François / Zoulim, Fabien / Hot, Arnaud / Fauter, Maxime / Drissi-Bakhkhat, Ayoub / Durieu, Isabelle / Lega, Jean-Christophe / Jamilloux, Yvan / Sève, Pascal

Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG

2023 Volume 40, Issue 3, Page(s) e2023031

Abstract: Background and aim: Granulomatous hepatitis (GH) is associated with various aetiologies, especially inflammatory and infectious disorders. Sarcoidosis is a granulomatous disease in which the liver is the fourth most affected organ. Since epithelioid ... ...

Abstract	Background and aim: Granulomatous hepatitis (GH) is associated with various aetiologies, especially inflammatory and infectious disorders. Sarcoidosis is a granulomatous disease in which the liver is the fourth most affected organ. Since epithelioid cell granulomas are not specific to sarcoidosis and since most patients with hepatic sarcoidosis are asymptomatic, valuable diagnostic biomarkers are needed to support the diagnosis of sarcoidosis. This study proposes to assess the diagnostic value of serum angiotensin converting enzyme (sACE) and lymphopenia in GH for sarcoidosis. Methods: We retrospectively analyzed the records of 90 patients referred to the internal medicine or hepatogastroenterology departments of the Lyon University Hospital (Lyon, France) between March 2002 and January 2020 in a context of GH. Results: In our tertiary center, 38 patients with sarcoidosis were identified among 73 patients with GH. Lymphopenia had a high specificity (85.7%), which increased when combined with elevated (97.0%). Interestingly, specificity increased in patients under 50 years old (100%). Conclusions: Those results suggests that lymphopenia and sACE may be valuable biomarkers for sarcoidosis diagnosis in GH when combined, especially in younger patients.
Language	English
Publishing date	2023-09-13
Publishing country	Italy
Document type	Journal Article
ZDB-ID	1339192-6
ISSN	2532-179X ; 1124-0490
ISSN (online)	2532-179X
ISSN	1124-0490
DOI	10.36141/svdld.v40i3.14221
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Article ; Online: Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions.

Jamilloux, Yvan / Henry, Thomas / Belot, Alexandre / Viel, Sébastien / Fauter, Maxime / El Jammal, Thomas / Walzer, Thierry / François, Bruno / Sève, Pascal

Autoimmunity reviews

2020 Volume 19, Issue 7, Page(s) 102567

Abstract: The coronavirus disease-19 pandemic (COVID-19), which appeared in China in December 2019 and rapidly spread throughout the world, has forced clinicians and scientists to take up extraordinary challenges. This unprecedented situation led to the inception ... ...

Abstract	The coronavirus disease-19 pandemic (COVID-19), which appeared in China in December 2019 and rapidly spread throughout the world, has forced clinicians and scientists to take up extraordinary challenges. This unprecedented situation led to the inception of numerous fundamental research protocols and many clinical trials. It quickly became apparent that although COVID-19, in the vast majority of cases, was a benign disease, it could also develop a severe form with sometimes fatal outcomes. Cytokines are central to the pathophysiology of COVID-19; while some of them are beneficial (type-I interferon, interleukin-7), others appear detrimental (interleukin-1β, -6, and TNF-α) particularly in the context of the so-called cytokine storm. Yet another characteristic of the disease has emerged: concomitant immunodeficiency, notably involving impaired type-I interferon response, and lymphopenia. This review provides an overview of current knowledge on COVID-19 immunopathology. We discuss the defective type-I IFN response, the theoretical role of IL-7 to restore lymphocyte repertoire, as well as we mention the two patterns observed in severe COVID-19 (i.e. interleukin-1β-driven macrophage activation syndrome vs. interleukin-6-driven immune dysregulation). Next, reviewing current evidence drawn from clinical trials, we examine a number of cytokine and anti-cytokine therapies, including interleukin-1, -6, and TNF inhibitors, as well as less targeted therapies, such as corticosteroids, chloroquine, or JAK inhibitors.
MeSH term(s)	Betacoronavirus ; COVID-19 ; Coronavirus Infections/drug therapy ; Coronavirus Infections/immunology ; Coronavirus Infections/therapy ; Cytokines/antagonists & inhibitors ; Cytokines/therapeutic use ; Humans ; Interferons/therapeutic use ; Interleukin-1beta ; Interleukin-6 ; Pandemics ; Pneumonia, Viral/immunology ; Pneumonia, Viral/therapy ; SARS-CoV-2 ; COVID-19 Drug Treatment
Chemical Substances	Cytokines ; IL1B protein, human ; IL6 protein, human ; Interleukin-1beta ; Interleukin-6 ; Interferons (9008-11-1)
Keywords	covid19
Language	English
Publishing date	2020-05-04
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2144145-5
ISSN	1873-0183 ; 1568-9972
ISSN (online)	1873-0183
ISSN	1568-9972
DOI	10.1016/j.autrev.2020.102567
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Article ; Online: Low glycosylated ferritin is a sensitive biomarker of severe COVID-19.

Fauter, Maxime / Viel, Sébastien / Zaepfel, Sabine / Pradat, Pierre / Fiscus, Julie / Villard, Marine / Garnier, Lorna / Walzer, Thierry / Sève, Pascal / Henry, Thomas / Jamilloux, Yvan

Cellular & molecular immunology

2020 Volume 17, Issue 11, Page(s) 1183–1185

MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Betacoronavirus/physiology ; Biomarkers/blood ; COVID-19 ; Coronavirus Infections/diagnosis ; Disease Progression ; Female ; Ferritins/blood ; Hospitalization ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral/diagnosis ; Prospective Studies ; SARS-CoV-2
Chemical Substances	Biomarkers ; glycosylated ferritin ; Ferritins (9007-73-2)
Keywords	covid19
Language	English
Publishing date	2020-09-11
Publishing country	China
Document type	Journal Article
ZDB-ID	2435097-7
ISSN	2042-0226 ; 1672-7681
ISSN (online)	2042-0226
ISSN	1672-7681
DOI	10.1038/s41423-020-00544-0
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Article ; Online: Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions

Jamilloux, Yvan / Henry, Thomas / Belot, Alexandre / Viel, Sébastien / Fauter, Maxime / El Jammal, Thomas / Walzer, Thierry / François, Bruno / Sève, Pascal

Autoimmunity Reviews

2020 Volume 19, Issue 7, Page(s) 102567

Keywords	Immunology ; Immunology and Allergy ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ZDB-ID	2144145-5
ISSN	1568-9972
ISSN	1568-9972
DOI	10.1016/j.autrev.2020.102567
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Article: Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions

Jamilloux, Yvan / Henry, Thomas / Belot, Alexandre / Viel, Sébastien / Fauter, Maxime / El Jammal, Thomas / Walzer, Thierry / François, Bruno / Sève, Pascal

Autoimmun Rev

Abstract	The coronavirus disease-19 pandemic (COVID-19), which appeared in China in December 2019 and rapidly spread throughout the world, has forced clinicians and scientists to take up extraordinary challenges. This unprecedented situation led to the inception of numerous fundamental research protocols and many clinical trials. It quickly became apparent that although COVID-19, in the vast majority of cases, was a benign disease, it could also develop a severe form with sometimes fatal outcomes. Cytokines are central to the pathophysiology of COVID-19; while some of them are beneficial (type-I interferon, interleukin-7), others appear detrimental (interleukin-1ß, -6, and TNF-α) particularly in the context of the so-called cytokine storm. Yet another characteristic of the disease has emerged: concomitant immunodeficiency, notably involving impaired type-I interferon response, and lymphopenia. This review provides an overview of current knowledge on COVID-19 immunopathology. We discuss the defective type-I IFN response, the theoretical role of IL-7 to restore lymphocyte repertoire, as well as we mention the two patterns observed in severe COVID-19 (i.e. interleukin-1ß-driven macrophage activation syndrome vs. interleukin-6-driven immune dysregulation). Next, reviewing current evidence drawn from clinical trials, we examine a number of cytokine and anti-cytokine therapies, including interleukin-1, -6, and TNF inhibitors, as well as less targeted therapies, such as corticosteroids, chloroquine, or JAK inhibitors.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #165401
Database	COVID19

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Article ; Online: Fast diagnostic test for familial Mediterranean fever based on a kinase inhibitor.

Magnotti, Flora / Malsot, Tiphaine / Georgin-Lavialle, Sophie / Abbas, Fatima / Martin, Amandine / Belot, Alexandre / Fauter, Maxime / Rabilloud, Muriel / Gerfaud-Valentin, Mathieu / Sève, Pascal / Duquesne, Agnes / Hot, Arnaud / Durupt, Stephane / Savey, Léa / Giurgea, Irina / Grateau, Gilles / Henry, Thomas / Jamilloux, Yvan

Annals of the rheumatic diseases

2020 Volume 80, Issue 1, Page(s) 128–132

Abstract: Background and objective: Familial Mediterranean fever (FMF) is the most frequent hereditary autoinflammatory disease. Its diagnosis relies on a set of clinical criteria and a genetic confirmation on identification of biallelic pathogenic : Methods: ... ...

Abstract	Background and objective: Familial Mediterranean fever (FMF) is the most frequent hereditary autoinflammatory disease. Its diagnosis relies on a set of clinical criteria and a genetic confirmation on identification of biallelic pathogenic Methods: Real-time pyroptosis and IL-1β secretion were monitored in response to UCN-01 in monocytes from FMF patients (n=67), HD (n=71) and OID patients (n=40). Sensitivity and specificity of the resulting diagnostic tests were determined by receiver operating characteristic curve analyses. Results: Inflammasome monitoring in response to UCN-01 discriminates FMF patients from other individuals. Pyroptosis assessment leads to a fast FMF diagnosis while combining pyroptosis and IL-1β dosage renders UCN-01-based assays highly sensitive and specific. UCN-01-triggered monocytes responses were influenced by Conclusions: UCN-01-based inflammasome assays could be used to rapidly diagnose FMF, with high sensitivity and specificity.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Arthritis, Juvenile/diagnosis ; Behcet Syndrome/diagnosis ; Case-Control Studies ; Child ; Child, Preschool ; Cryopyrin-Associated Periodic Syndromes/diagnosis ; Familial Mediterranean Fever/diagnosis ; Familial Mediterranean Fever/genetics ; Familial Mediterranean Fever/immunology ; Female ; Fever/diagnosis ; Fever of Unknown Origin/diagnosis ; Hereditary Autoinflammatory Diseases/diagnosis ; Humans ; Immunologic Tests/methods ; Inflammasomes/drug effects ; Inflammasomes/immunology ; Inflammasomes/metabolism ; Interleukin-1beta/drug effects ; Interleukin-1beta/immunology ; Interleukin-1beta/metabolism ; Lupus Erythematosus, Systemic/diagnosis ; Male ; Mevalonate Kinase Deficiency/diagnosis ; Middle Aged ; Monocytes/drug effects ; Monocytes/immunology ; Monocytes/metabolism ; Protein Kinase Inhibitors/pharmacology ; Pyrin/drug effects ; Pyrin/genetics ; Pyrin/immunology ; Pyrin/metabolism ; Pyroptosis/drug effects ; Sensitivity and Specificity ; Sepsis/diagnosis ; Staurosporine/analogs & derivatives ; Staurosporine/pharmacology ; Still's Disease, Adult-Onset/diagnosis ; Young Adult
Chemical Substances	IL1B protein, human ; Inflammasomes ; Interleukin-1beta ; MEFV protein, human ; Protein Kinase Inhibitors ; Pyrin ; 7-hydroxystaurosporine (7BU5H4V94A) ; Staurosporine (H88EPA0A3N)
Language	English
Publishing date	2020-10-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	7090-7
ISSN	1468-2060 ; 0003-4967
ISSN (online)	1468-2060
ISSN	0003-4967
DOI	10.1136/annrheumdis-2020-218366
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Article: Low glycosylated ferritin is a sensitive biomarker of severe COVID-19

Fauter, Maxime / Viel, Sébastien / Zaepfel, Sabine / Pradat, Pierre / Fiscus, Julie / Villard, Marine / Garnier, Lorna / Walzer, Thierry / Sève, Pascal / Henry, Thomas / Jamilloux, Yvan

Cell Mol Immunol

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #759586
Database	COVID19

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