Transmission of familial Mediterranean fever mutations following bone marrow transplantation

Touitou, Isabelle; Dumont, Bénédicte; Pourtein, Monique; Perelman, S; Sirvent, Ana Esther; Soler, C

doi:10.1111/j.1399-0004.2007.00840.x

Cited by 5 publications

(5 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A gain-of-function, leading to an increase in the maturation of proinflammatory cytokines to their secreted forms, was suggested to explain the pathogenicity of these conservative missense MEFV mutations [ 8 , 9 ]. A case of transmission of FMF by bone marrow transplantation from a donor with undiagnosed FMF proved the disease could be acquired through MEFV mutated hematopoietic cells [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Acquired familial Mediterranean fever associated with a somatic MEFV mutation in a patient with JAK2 associated post-polycythemia myelofibrosis

Shinar

Tohami

Livneh

et al. 2015

Orphanet J Rare Dis

View full text Add to dashboard Cite

BackgroundA study was designed to identify the source of fever in a patient with post-polycythemia myelofibrosis, associated with clonal Janus Kinase 2 (JAK2) mutation involving duplication of exon 12. The patient presented with 1–2 day long self-limited periodic episodes of high fever that became more frequent as the hematologic disease progressed.MethodsAfter ruling out other causes for recurrent fever, analysis of the pyrin encoding Mediterranean fever gene (MEFV) was carried out by Sanger sequencing in peripheral blood DNA samples obtained 4 years apart, in buccal cells, laser dissected kidney tubular cells, and FACS-sorted CD3-positive or depleted mononucleated blood cells. Hematopoeitc cells results were validated by targeted deep sequencing. A Sanger sequence based screen for pathogenic variants of the autoinflammatory genes NLRP3, TNFRSF1A and MVK was also performed.ResultsA rare, c.1955G>A, p.Arg652His MEFV gene variant was identified at negligible levels in an early peripheral blood DNA sample, but affected 46 % of the MEFV alleles and was restricted to JAK2-positive, polymorphonuclear and CD3-depleted mononunuclear DNA samples obtained 4 years later, when the patient experienced fever bouts. The patient was also heterozygous for the germ line, non-pathogenic NLRP3 gene variant, p.Q705K. Upon the administration of colchicine, the gold standard treatment for familial Mediterranean fever (FMF), the fever attacks subsided.ConclusionsThis is the first report of non-transmitted, acquired FMF, associated with a JAK2 driven clonal expansion of a somatic MEFV exon 10 mutation. The non-pathogenic germ line NLRP3 p.Q705K mutation possibly played a modifier role on the disease phenotype.

show abstract

Section: Introductionmentioning

confidence: 99%

Acquired familial Mediterranean fever associated with a somatic MEFV mutation in a patient with JAK2 associated post-polycythemia myelofibrosis

Shinar

Tohami

Livneh

et al. 2015

Orphanet J Rare Dis

View full text Add to dashboard Cite

show abstract

“…Therefore, the results of critical immunological, cytokine profiling, and genotyping tests should ideally be available before the decision for HSCT is reached [152,153 ▪ ]. Experience is supporting use of RIC regimens, and preferring a healthy matched unrelated donor over family members and/or matched unrelated umbilical cord donors when the disease-causing gene mutation is unknown [16 ▪▪ ,17,154–155,156 ▪▪ ]. Other cell-based therapies such as mesenchymal stromal cells and gene editing and/or therapy for monogenic disorders are promising new breakthroughs [94,157,158].…”

Section: Discussionmentioning

confidence: 99%

Haematopoietic stem cell transplantation in paediatric rheumatic disease

Abinun

Slatter

2021

Current Opinion in Rheumatology

View full text Add to dashboard Cite

Purpose of reviewA small proportion of children affected by rheumatic diseases suffer from severe, progressive disease, resistant to conventional antirheumatic therapies and to biologic agents interfering with inflammatory cytokines, costimulatory molecules expressed on immune system cells and intracellular signalling pathways. Adding to the poor prognosis is a high risk from significant morbidity and mortality associated with longterm treatment with multiple, often combined anti-inflammatory and immunosuppressive agents. Carefully selected patients from this unfortunate group may benefit from treatment with haematopoietic stem cell transplantation. Recent findingsThe majority of patients with severe paediatric rheumatic and autoinflammatory diseases treated with autologous and/or allogeneic haematopoietic stem cell transplantation achieved long-term remission. However, the incidence of disease relapse and transplant related morbidity and mortality is still significant. SummaryCareful patient and donor selection, timing of the transplant earlier in the course of disease rather than the 'last resort' and choosing the most suitable conditioning regimen for each individual patient are the major factors favouring successful outcome. Close co-operation between the patients, their family, and involved medical teams is essential. Keywords auto-inflammatory diseases, complete remission, disease relapse, haematopoietic stem cell transplantation, paediatric rheumatic diseases, transplant-related mortality && ]. For such children, the only treatment option is haematopoietic stem cell transplantation (HSCT), often referred to as the 'last resort' or 'salvage' therapy [12,13].

show abstract

“…Reports regarding the transmission of FMF from a donor after allogeneic BMT for idiopathic aplastic anemia 6,7 imply that pyrin dysregulation induced by hematopoietic cells, presumably myeloid cells, originated from the donor can cause symptoms of FMF. In addition, a report concerning an FMF patient cured of coexisting congenital dyserythropoietic anemia by allogeneic BMT 15 suggests that hematopoietic cells overexpressing pyrin aberrantly may play a pivotal role in the pathogenesis of FMF.…”

Section: Discussionmentioning

confidence: 99%

“…Some reports regarding the transmission of FMF from donors suffering from FMF with p.M694V mutation after bone marrow transplantation (BMT) have been published. 6,7 Here, we report for the first time a patient with FMF harboring the same heterozygous p.E148Q genotype originating from both donor and recipient cells after second cord blood transplantation (CBT) for a relapse of familial hemophagocytic lymphohistiocytosis (FHL). The p.E148Q mutation remains to be directly linked to the phenotype of FMF.…”

mentioning

confidence: 99%

Familial Mediterranean Fever After Cord Blood Transplantation for Familial Hemophagocytic Lymphohistiocytosis

Igarashi

Hori²,

Yamamoto³

et al. 2021

Journal of Pediatric Hematology/Oncology

View full text Add to dashboard Cite

Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disorder accompanied by periodic fever and sterile serositis. We report a 5-year-old boy with FMF, who underwent second unrelated cord blood transplantation (CBT) for recurrent familial hemophagocytic lymphohistiocytosis. Periodic attacks of fever and abdominal pain started 6 months after CBT. He was diagnosed with FMF according to the Tel-Hashomer criteria and treated successfully with colchicine. Genetic testing showed heterozygous p.E148Q mutation in the MEFV gene from both donor and recipient cells. Several CBT-related factors including use of an immunosuppressant can potentially be involved in the pathogenesis of FMF in our patient.

show abstract

Transmission of familial Mediterranean fever mutations following bone marrow transplantation

Cited by 5 publications

References 10 publications

Acquired familial Mediterranean fever associated with a somatic MEFV mutation in a patient with JAK2 associated post-polycythemia myelofibrosis

Acquired familial Mediterranean fever associated with a somatic MEFV mutation in a patient with JAK2 associated post-polycythemia myelofibrosis

Haematopoietic stem cell transplantation in paediatric rheumatic disease

Familial Mediterranean Fever After Cord Blood Transplantation for Familial Hemophagocytic Lymphohistiocytosis

Contact Info

Product

Resources

About