scholarly journals Hemophagocytic Lymphohistiocytosis Gene Mutations in Adult Patients Presenting With CLIPPERS-Like Syndrome

2021 ◽  
Vol 8 (3) ◽  
pp. e970
Author(s):  
Guillaume Taieb ◽  
Elsa Kaphan ◽  
Claire Duflos ◽  
Christine Lebrun-Frénay ◽  
Valérie Rigau ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Brain Mri ◽  
Gene Mutations ◽  
Adult Onset ◽  
Cytotoxic Lymphocyte ◽  
Familial Hemophagocytic Lymphohistiocytosis ◽  
Non Hodgkin Lymphoma ◽  
Treatable Condition ◽  
Perforin Expression

ObjectiveTo determine whether adult cases of Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) may be related to familial hemophagocytic lymphohistiocytosis (HLH) causes, we have screened patients with adult-onset CLIPPERS for mutations in primary HLH-associated genes.MethodsIn our cohort of 36 patients fulfilling the criteria for probable or definite CLIPPERS according to the CLIPPERS-2017 criteria, we conducted a first study on 12 patients who consented to genetic testing. In these 12 patients, systemic HLH criteria were searched, and genetic analysis of 8 genes involved in primary HLH was performed.ResultsFour definite and 8 probable CLIPPERS were enrolled (n = 12). Mutations involved in HLH were identified in 2 definite and 2 probable CLIPPERS (4/12). Three of them had biallelic PRF1 mutations with reduced perforin expression in natural killer cells. The remaining patient had biallelic UNC13D mutations with cytotoxic lymphocyte impaired degranulation. None of the mutated patients reached the criteria for systemic HLH. During follow-up, 3 of them displayed atypical findings for CLIPPERS, including emergence of systemic non-Hodgkin lymphoma (1/3) and confluent gadolinium-enhancing lesions on brain MRI (3/3).ConclusionsIn our patients presenting with adult-onset CLIPPERS, one-third have HLH gene mutations. This genetic treatable condition should be searched in patients with CLIPPERS, especially in those presenting with atypical findings.

scholarly journals Down-regulation of CD5 expression on activated CD8+ T cells in familial hemophagocytic lymphohistiocytosis with perforin gene mutations

2013 ◽  
Vol 74 (12) ◽  
pp. 1579-1585 ◽  
Author(s):  
Taizo Wada ◽  
Yasuhisa Sakakibara ◽  
Ryosei Nishimura ◽  
Tomoko Toma ◽  
Yasuhisa Ueno ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Gene Mutations ◽  
Down Regulation ◽  
Familial Hemophagocytic Lymphohistiocytosis

scholarly journals Pediatric CNS-isolated hemophagocytic lymphohistiocytosis

2019 ◽  
Vol 6 (3) ◽  
pp. e560 ◽  
Author(s):  
Leslie A. Benson ◽  
Hojun Li ◽  
Lauren A. Henderson ◽  
Isaac H. Solomon ◽  
Ariane Soldatos ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Chart Review ◽  
Gene Mutations ◽  
Retrospective Chart Review ◽  
Germline Mutations ◽  
Accurate Diagnosis ◽  
Hematopoietic Stem ◽  
Familial Hemophagocytic Lymphohistiocytosis ◽  
Disease Remission

ObjectiveTo highlight a novel, treatable syndrome, we report 4 patients with CNS-isolated inflammation associated with familial hemophagocytic lymphohistiocytosis (FHL) gene mutations (CNS-FHL).MethodsRetrospective chart review.ResultsPatients with CNS-FHL are characterized by chronic inflammation restricted to the CNS that is not attributable to any previously described neuroinflammatory etiology and have germline mutations in known FHL-associated genes with no signs of systemic inflammation. Hematopoietic stem cell transplantation (HCT) can be well tolerated and effective in achieving or maintaining disease remission in patients with CNS-FHL.ConclusionsEarly and accurate diagnosis followed by treatment with HCT can reduce morbidity and mortality in CNS-FHL, a novel, treatable syndrome.Classification of evidenceThis study provides Class IV evidence that HCT is well tolerated and effective in treating CNS-FHL.

Novel spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis in ethnic omani patients

2007 ◽  
Vol 82 (12) ◽  
pp. 1099-1102 ◽  
Author(s):  
Shanmugakonar Muralitharan ◽  
Yasser A. Wali ◽  
David Dennison ◽  
Zakia A. Lamki ◽  
Mathew Zachariah ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Gene Mutations ◽  
Familial Hemophagocytic Lymphohistiocytosis

scholarly journals Defective cytotoxic lymphocyte degranulation in syntaxin-11–deficient familial hemophagocytic lymphohistiocytosis 4 (FHL4) patients

Blood ◽  
2007 ◽  
Vol 110 (6) ◽  
pp. 1906-1915 ◽  
Author(s):  
Yenan T. Bryceson ◽  
Eva Rudd ◽  
Chengyun Zheng ◽  
Josefine Edner ◽  
Daoxin Ma ◽  
...  
Keyword(s):  
Nk Cells ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Nk Cell ◽  
Severe Disease ◽  
Target Cells ◽  
Loss Of Function ◽  
Cytotoxic Lymphocyte ◽  
Familial Hemophagocytic Lymphohistiocytosis ◽  
Genes Encoding ◽  
Syntaxin 11

Abstract Familial hemophagocytic lymphohistiocytosis (FHL) is typically an early onset, fatal disease characterized by a sepsislike illness with cytopenia, hepatosplenomegaly, and deficient lymphocyte cytotoxicity. Disease-causing mutations have been identified in genes encoding perforin (PRF1/FHL2), Munc13-4 (UNC13D/FHL3), and syntaxin-11 (STX11/FHL4). In contrast to mutations leading to loss of perforin and Munc13-4 function, it is unclear how syntaxin-11 loss-of-function mutations contribute to disease. We show here that freshly isolated, resting natural killer (NK) cells and CD8+ T cells express syntaxin-11. In infants, NK cells are the predominant perforin-containing cell type. NK cells from FHL4 patients fail to degranulate when encountering susceptible target cells. Unexpectedly, IL-2 stimulation partially restores degranulation and cytotoxicity by NK cells, which could explain the less severe disease progression observed in FHL4 patients, compared with FHL2 and FHL3 patients. Since the effector T-cell compartment is still immature in infants, our data suggest that the observed defect in NK-cell degranulation may contribute to the pathophysiology of FHL, that evaluation of NK-cell degranulation in suspected FHL patients may facilitate diagnosis, and that these new insights may offer novel therapeutic possibilities.

scholarly journals CMET-37. CLINICAL UTILITY OF ENCYCLOPEDIC TUMOR ANALYSIS TO TREAT PATIENTS WITH BRAIN METASTASIS IN REFRACTORY CANCERS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi59-vi60
Author(s):  
Timothy Crook ◽  
Darshana Patil ◽  
Dadasaheb Akolkar ◽  
Anantbhushan Ranade ◽  
Amit Bhatt ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Treatment Options ◽  
Brain Mri ◽  
Gene Mutations ◽  
Solid Organ ◽  
Pet Ct ◽  
The Impact

Abstract Brain metastasis in solid organ cancers is associated with adverse prognosis, which is further aggravated by limited systemic treatment options. Such patients are also often excluded from clinical trials since their poor prognosis is perceived to unfavorably impact trial outcomes and misrepresent efficacy data. We retrospectively evaluated the efficacy of treatment guided by Encyclopedic Tumor Analysis (ETA) in patients with advanced refractory malignancies and brain metastases to determine the impact on outcomes. Freshly biopsied tumor tissue (primary / lymph node / liver) and peripheral blood of patients were used for integrational multi-analyte investigations as part of ETA, which included gene mutations, gene expression, and in vitro chemosensitivity profiling of viable tumor cells. Based on ETA, patients received individualized therapy recommendations. All patients underwent a PET-CT scan as well as MRI scan prior to treatment start to determine extent of disease. All patients underwent follow-up PET-CT scans and brain MRI scans every 6–8 weeks. Of the ten patients with brain metastases, which were evaluated after receiving ETA-guided treatment, the median follow-up duration was 97 days (range 79 – 180 days) during which all ten patients remained progression-free. Median time to progression for these patients on the last (failed) line of treatment was 91 days (range 30 - 176 days). Five patients showed partial response and five patients showed stable disease while on ETA-guided treatment. During the follow-up period, all brain metastases were either stable (n=7) or had regressed (n=3), and none of the patients reported new brain lesions. Personalized ETA guided treatments imparted clinical benefit by halting disease progression in this cohort of high-risk patients who would have otherwise been considered for palliative regimens due to perceived unfavorable prognosis.

Low-Frequency Sensorineural Hearing Loss in Familial Hemophagocytic Lymphohistiocytosis Type 5

2018 ◽  
Vol 127 (6) ◽  
pp. 409-413 ◽  
Author(s):  
Aren Bezdjian ◽  
Hanneke Bruijnzeel ◽  
Julia Pagel ◽  
Sam J. Daniel ◽  
Hans G.X.M. Thomeer
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Survival Rates ◽  
Low Frequency ◽  
Sensorineural Hearing ◽  
Hematopoietic Stem ◽  
Familial Hemophagocytic Lymphohistiocytosis

Introduction: Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive disease affecting the cytotoxic pathway. Due to the recent advances in molecular diagnosis, immuno-chemo therapy, and hematopoietic stem cell transplantation treatment, FHL survival rates have drastically increased. Case Presentation: Herein, we describe a case of FHL type 5 presenting with low-frequency sensorineural hearing loss. Alongside our reported case, 6 additional patients were identified in the literature. Management and Outcome: The progressive nature of FHL disorder may cause bilateral, low-frequency, irreversible sensorineural hearing loss. This type of hearing loss should be considered among the long-term sequelea presenting with FHL5. Discussion: We recommend audiological evaluation at initial FHL5 diagnosis to assess for hearing functions. Follow-up in audiology should be part of the long-term monitoring of patients with FHL5 as hearing loss could develop long after diagnosis.

scholarly journals An inframe perforin gene deletion in familial hemophagocytic lymphohistiocytosis is associated with perforin expression

2004 ◽  
Vol 78 (1) ◽  
pp. 59-63 ◽  
Author(s):  
Shanmugakonar Muralitharan ◽  
Zakia Al Lamki ◽  
David Dennison ◽  
Brian Sidney Christie ◽  
Yasser A. Wali ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Gene Deletion ◽  
Familial Hemophagocytic Lymphohistiocytosis ◽  
Perforin Expression

Prenatal diagnosis of perforin gene mutations in familial hemophagocytic lymphohistiocytosis (FHLH)

2002 ◽  
Vol 22 (1) ◽  
pp. 80-81 ◽  
Author(s):  
Udo zur Stadt ◽  
Michael Pruggmayer ◽  
Helena Jung ◽  
Jan-Inge Henter ◽  
Marion Schneider ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Gene Mutations ◽  
Familial Hemophagocytic Lymphohistiocytosis
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