Browsing by Author "Neves, JF"
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- Case Report: Primary Immunodeficiencies, Massive EBV+ T-Cell Lympoproliferation Leading to the Diagnosis of ICF2 SyndromePublication . Padeira, GL; Araújo, C; Cordeiro, AI; Freixo, J; Martins, CG; Neves, JFIn immunocompromised patients, EBV may elicit B-cell transformation and proliferation. A 5-year-old microcephalic boy was admitted with fever and non-malignant polymorphic T-cell lymphoproliferative disease associated with EBV. A presumptive diagnosis of primary immunodeficiency with inability to control EBV was made and next-generation sequencing led to the identification of a novel ZBTB24 mutation (ICF2-syndrome). This case shows that susceptibility to EBV seems to be particular of ICF-2 as it has not been described in the other types of ICF. It is mandatory to raise the hypothesis of an underlying PID in case of severe EBV infection.
- Case Report: Wide Spectrum of Manifestations of Ligase IV Deficiency: Report of 3 CasesPublication . Costa e Castro, A; Maia, R; Batalha, S; Freixo, JP; Martins, C; Neves, C; Cordeiro, AI; Neves, JFDNA ligase IV deficiency is a rare autosomal recessive disorder associated with impaired DNA repair mechanisms. Most patients with DNA repair defects present with neurologic deficits, combined immunodeficiency, bone marrow failure, and/or hematologic neoplasia. We present 3 unrelated cases of ligase IV deficiency with different clinical presentations. Patient 1 presented at the age of 5 with bone marrow failure, dysmorphic features, and T and B lymphopenia. A compound heterozygous variant L19W/K635fs in the LIG4 gene was identified. Patient 2 presented at the age of 16 with recurrent infections. He had agammaglobulinemia and absent B cells. A homozygous R278H in the LIG4 gene was identified. Patient 3 was referred for vitiligo and B-cell lymphopenia (low class-switched B cells) and hypogammaglobulinemia. Homozygous R278H in LIG4 was also identified. In the last few years, the spectrum of clinical manifestations caused by ligase IV deficiency has widened, making it very difficult to establish an accurate clinical diagnosis. The use of NGS allows a proper diagnosis and provides a better prognosis and adequate family counseling.
- Characterization of the Clinical and Immunologic Phenotype and Management of 157 Individuals with 56 Distinct Heterozygous NFKB1 MutationsPublication . Lorenzini, T; Fliegauf, M; Klammer, N; Frede, N; Proietti, M; Bulashevska, A; Camacho-Ordonez, N; Varjosalo, M; Kinnunen, M; de Vries, E; van der Meer, JW; Ameratunga, R; Roifman, CM; Schejter, YD; Kobbe, R; Hautala, T; Atschekzei, F; Schmidt, RE; Schröder, C; Stepensky, P; Shadur, B; Pedroza, LA; van der Flier, M; Martínez-Gallo, M; Gonzalez-Granado, LI; Allende, LM; Shcherbina, A; Kuzmenko, N; Zakharova, V; Neves, JF; Svec, P; Fischer, U; Ip, W; Bartsch, O; Barış, S; Klein, C; Geha, R; Chou, J; Alosaimi, M; Weintraub, L; Boztug, K; Hirschmugl, T; Dos Santos Vilela, MM; Holzinger, D; Seidl, M; Lougaris, V; Plebani, A; Alsina, L; Piquer-Gibert, M; Deyà-Martínez, A; Slade, CA; Aghamohammadi, A; Abolhassani, H; Hammarström, L; Kuismin, O; Helminen, M; Allen, HL; Thaventhiran, JE; Freeman, AF; Cook, M; Bakhtiar, s; Christiansen, M; Cunningham-Rundles, C; Patel, NC; Rae, W; Niehues, T; Brauer, N; Syrjänen, J; Seppänen, MJ; Burns, SO; Tuijnenburg, P; Kuijpers, TW; Warnatz, K; Grimbacher, BBackground: An increasing number of NFKB1 variants are being identified in patients with heterogeneous immunologic phenotypes. Objective: To characterize the clinical and cellular phenotype as well as the management of patients with heterozygous NFKB1 mutations. Methods: In a worldwide collaborative effort, we evaluated 231 individuals harboring 105 distinct heterozygous NFKB1 variants. To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling. Results: We classified 56 of the 105 distinct NFKB1 variants in 157 individuals from 68 unrelated families as pathogenic. Incomplete clinical penetrance (70%) and age-dependent severity of NFKB1-related phenotypes were observed. The phenotype included hypogammaglobulinemia (88.9%), reduced switched memory B cells (60.3%), and respiratory (83%) and gastrointestinal (28.6%) infections, thus characterizing the disorder as primary immunodeficiency. However, the high frequency of autoimmunity (57.4%), lymphoproliferation (52.4%), noninfectious enteropathy (23.1%), opportunistic infections (15.7%), autoinflammation (29.6%), and malignancy (16.8%) identified NF-κB1-related disease as an inborn error of immunity with immune dysregulation, rather than a mere primary immunodeficiency. Current treatment includes immunoglobulin replacement and immunosuppressive agents. Conclusions: We present a comprehensive clinical overview of the NF-κB1-related phenotype, which includes immunodeficiency, autoimmunity, autoinflammation, and cancer. Because of its multisystem involvement, clinicians from each and every medical discipline need to be made aware of this autosomal-dominant disease. Hematopoietic stem cell transplantation and NF-κB1 pathway-targeted therapeutic strategies should be considered in the future.
- Congenital Nephrotic Syndrome in IL7Rα-SCID: A Rare Feature of Maternofetal Graft-Versus-Host DiseasePublication . Tsilifis, C; Slatter, M; Cordeiro, AI; Hambleton, S; Engelhardt, KR; Griffin, H; Gennery, AR; Neves, JF
- Fatal Central Nervous System Lymphocytic Vasculitis after Treatment for Burkitt Lymphoma in a Patient with a SH2D1A MutationPublication . Neves, JF; Raga, LT; Chiang, SCC; Tesi, B; Vieira, JP; Cordeiro, AI; Borrego, L; Bryceson, YTVery rarely, patients with X-linked lymphoproliferative syndrome type 1 present central nervous system vasculitis. We report a patient carrying a SH2D1A mutation that, after treatment for lymphoma developed fatal central nervous system vasculitis. He lacked signs of ongoing Epstein-Barr virus infection. We propose that impaired T cell homeostasis caused by SAP deficiency facilitates aberrant CD8 T cell activation against vascular antigens promoting clinical manifestations.
- Fatal Meningitis in Patient with X-Linked Chronic Granulomatous Disease Caused by Virulent Granulibacter bethesdensisPublication . Rebelo, M; Ding, L; Cordeiro, AI; Neves, C; Simões, MJ; Zelazny, AM; Holland, SM; Neves, JFGranulibacter bethesdensis is a pathogen reported to cause recurrent lymphadenitis exclusively in persons with chronic granulomatous disease. We report a case of fatal meningitis caused by a highly virulent G. bethesdensis strain in an adolescent in Europe who had chronic granulomatous disease.
- H Factor Deficiency: A Case with an Atypical PresentationPublication . Rocha, AP; Borges, M; Neves, C; Neves, JFWe report a case of an 18-month-old boy with H factor deficiency with atypical presentation: recurrent acute otitis media and several maternal family members with autoimmune disorders (vitiligo, thyroiditis and immune trombocytopenia). Blood tests revealed low C3 and AH50, as well as low properdin and H factor. I factor was normal. CFH gene molecular test confirmed the H factor deficiency diagnosis. This child had none of the typical manifestations of this disorder, namely Neisseria meningitidis infection or renal disease (glomerulonephritis and atypical haemolytic uremic syndrome). Autoimmune family history and correct interpretation of blood tests' results were crucial for this diagnosis.
- Invasive Meningococcal Disease Unraveling a Novel Mutation in the C5 Gene in a Portuguese FamilyPublication . Marujo, F; Costa, LC; Duarte, R; Brito, MJ; Cordeiro, A; Neves, C; Neves, JFAlthough bacterial meningitis is a rare presentation of a congenital immunodeficiency, invasive meningococcal disease is classically associated with complement deficiencies. We report a patient from a consanguineous kindred presenting with an invasive meningococcal disease caused by serogroup B meningococcus that revealed an underlying C5 deficiency caused by a novel mutation in the C5 gene.
- Lemierre Syndrome in a Teenager Presenting as Pulmonary Septic EmbolismPublication . Domingues, R; Neves, JF; Candeias, F; Kjöllerström, P; Brito, MJLemierre syndrome is easily missed and may be more common than generally believed. Usually a complication of a deep neck abscess, it can present suddenly with shortness of breath and hypoxemia. Accurate diagnosis and orientation are mandatory for the treatment of an otherwise potentially life-threatening disease. We describe a case of an adolescent with Lemierre syndrome and septic pulmonary embolism.
- Novel IL2RG Mutation Causes Leaky TLOWB+NK+ SCID With Nodular Regenerative Hyperplasia and Normal IL-15 STAT5 PhosphorylationPublication . Neves, JF; Martins, C; Cordeiro, AI; Neves, C; Plagnol, V; Curtis, J; Fabre, M; Bibi, S; Borrego, LM; Moshous, D; Nejentsev, S; Gilmour, KX-linked severe combined immunodeficiency disease (SCID) is caused by mutations in the interleukin (IL)-2 receptor γ (IL2RG) gene and patients usually present with a TBNK SCID phenotype. Nevertheless, a minority of these patients present with a TBNK phenotype, similar to the IL-7R-deficient patients. We report a patient with a novel missense p.Glu297Gly mutation in the IL2RG gene presenting with a leaky TBNK SCID with delayed onset, moderate susceptibility to infections, and nodular regenerative hyperplasia. He presents with preserved STAT5 tyrosine phosphorylation in response to IL-15 stimulation but not in response to IL-2 and IL-7, resulting in the NK phenotype.