6 results on '"Csomos K"'
Search Results
2. Clinical and Treatment History of Patients with Partial DiGeorge Syndrome and Autoimmune Cytopenia at Multiple Centers.
- Author
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Patel PK, Chinga ML, Yilmaz M, Joychan S, Ujhazi B, Ellison M, Gordon S, Nieves D, Csomos K, Eslin D, Afify ZA, Meznarich J, Bohnsack J, Walkovich K, Seidel MG, Sharapova S, Boyarchyk O, Latysheva E, Tuzankina I, Shaker AB, Ayala I, Sriaroon P, Westermann-Clark E, and Walter JE
- Subjects
- Humans, Retrospective Studies, Antigens, CD19, Disease Progression, DiGeorge Syndrome diagnosis, DiGeorge Syndrome therapy, Cytopenia
- Abstract
Background: Patients with partial DiGeorge syndrome (pDGS) can present with immune dysregulation, the most common being autoimmune cytopenia (AIC). There is a lack of consensus on the approach to type, combination, and timing of therapies for AIC in pDGS. Recognition of immune dysregulation early in pDGS clinical course may help individualize treatment and prevent adverse outcomes from chronic immune dysregulation., Objectives: Objectives of this study were to characterize the natural history, immune phenotype, and biomarkers in pDGS with AIC., Methods: Data on clinical presentation, disease severity, immunological phenotype, treatment selection, and response for patients with pDGS with AIC were collected via retrospective chart review. Flow cytometric analysis was done to assess T and B cell subsets, including biomarkers of immune dysregulation., Results: Twenty-nine patients with the diagnosis of pDGS and AIC were identified from 5 international institutions. Nineteen (62%) patients developed Evan's syndrome (ES) during their clinical course and twenty (69%) had antibody deficiency syndrome. These patients demonstrated expansion in T follicular helper cells, CD19
hi CD21lo B cells, and double negative cells and reduction in CD4 naïve T cells and regulatory T cells. First-line treatment for 17/29 (59%) included corticosteroids and/or high-dose immunoglobulin replacement therapy. Other overlapping therapies included eltrombopag, rituximab, and T cell immunomodulators., Conclusions: AIC in pDGS is often refractory to conventional AIC treatment paradigms. Biomarkers may have utility for correlation with disease state and potentially even response to therapy. Immunomodulating therapies could be initiated early based on early immune phenotyping and biomarkers before the disease develops or significantly worsens., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2024
- Full Text
- View/download PDF
3. Disease Progression of WHIM Syndrome in an International Cohort of 66 Pediatric and Adult Patients.
- Author
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Geier CB, Ellison M, Cruz R, Pawar S, Leiss-Piller A, Zmajkovicova K, McNulty SM, Yilmaz M, Evans MO 2nd, Gordon S, Ujhazi B, Wiest I, Abolhassani H, Aghamohammadi A, Barmettler S, Bhar S, Bondarenko A, Bolyard AA, Buchbinder D, Cada M, Cavieres M, Connelly JA, Dale DC, Deordieva E, Dorsey MJ, Drysdale SB, Ehl S, Elfeky R, Fioredda F, Firkin F, Förster-Waldl E, Geng B, Goda V, Gonzalez-Granado L, Grunebaum E, Grzesk E, Henrickson SE, Hilfanova A, Hiwatari M, Imai C, Ip W, Jyonouchi S, Kanegane H, Kawahara Y, Khojah AM, Kim VH, Kojić M, Kołtan S, Krivan G, Langguth D, Lau YL, Leung D, Miano M, Mersyanova I, Mousallem T, Muskat M, Naoum FA, Noronha SA, Ouederni M, Ozono S, Richmond GW, Sakovich I, Salzer U, Schuetz C, Seeborg FO, Sharapova SO, Sockel K, Volokha A, von Bonin M, Warnatz K, Wegehaupt O, Weinberg GA, Wong KJ, Worth A, Yu H, Zharankova Y, Zhao X, Devlin L, Badarau A, Csomos K, Keszei M, Pereira J, Taveras AG, Beaussant-Cohen SL, Ong MS, Shcherbina A, and Walter JE
- Subjects
- Humans, Receptors, CXCR4 genetics, Disease Progression, Immunologic Deficiency Syndromes diagnosis, Immunologic Deficiency Syndromes epidemiology, Immunologic Deficiency Syndromes genetics, Warts diagnosis, Warts epidemiology, Warts genetics, Agammaglobulinemia genetics, Neutropenia genetics, Lymphopenia complications
- Abstract
Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not diagnosed until adulthood. The prevalence and mean age of recognition and/or onset of clinical manifestations within our cohort were infections 88%/1.6 years, neutropenia 98%/3.8 years, lymphopenia 88%/5.0 years, and warts 40%/12.1 years. However, we report greater prevalence and variety of autoimmune complications of WHIM syndrome (21.2%) than reported previously. Patients with versus without family history of WHIM syndrome were diagnosed earlier (22%, average age 1.3 years versus 78%, average age 5 years, respectively). Patients with a family history of WHIM syndrome also received earlier treatment, experienced less hospitalization, and had less end-organ damage. This observation reinforces previous reports that early treatment for WHIM syndrome improves outcomes. Only one patient died; death was attributed to complications of hematopoietic stem cell transplantation. The variable expressivity of WHIM syndrome in pediatric patients delays their diagnosis and therapy. Early-onset bacterial infections with severe neutropenia and/or lymphopenia should prompt genetic testing for WHIM syndrome, even in the absence of warts., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
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4. Adult-Onset Myopathy in a Patient with Hypomorphic RAG2 Mutations and Combined Immune Deficiency.
- Author
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Henrickson SE, Walter JE, Quinn C, Kanakry JA, Bardakjian T, Dimitrova D, Ujhazi B, Csomos K, Bosticardo M, Dobbs K, Nasrallah M, Notarangelo LD, Holland SM, and Fadugba O
- Subjects
- Adult, Age of Onset, Biomarkers, Biopsy, Combined Modality Therapy, DNA Mutational Analysis, Humans, Immunologic Deficiency Syndromes diagnosis, Immunologic Deficiency Syndromes therapy, Male, Muscular Diseases diagnosis, Muscular Diseases therapy, Phenotype, Treatment Outcome, DNA-Binding Proteins genetics, Immunologic Deficiency Syndromes complications, Muscular Diseases complications, Muscular Diseases genetics, Mutation, Nuclear Proteins genetics
- Published
- 2018
- Full Text
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5. Ligase-4 Deficiency Causes Distinctive Immune Abnormalities in Asymptomatic Individuals.
- Author
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Felgentreff K, Baxi SN, Lee YN, Dobbs K, Henderson LA, Csomos K, Tsitsikov EN, Armanios M, Walter JE, and Notarangelo LD
- Subjects
- Adolescent, Adult, Agammaglobulinemia genetics, Agammaglobulinemia immunology, Cell Line, Cells, Cultured, Child, Female, Fibroblasts radiation effects, Granulocytes radiation effects, Humans, Leukocytes, Mononuclear cytology, Lymphocyte Count, Lymphocyte Subsets immunology, Male, Mutation, Radiation, Ionizing, Young Adult, DNA Ligase ATP genetics, Immunologic Deficiency Syndromes genetics, Immunologic Deficiency Syndromes immunology
- Abstract
Purpose: DNA Ligase 4 (LIG4) is a key factor in the non-homologous end-joining (NHEJ) DNA double-strand break repair pathway needed for V(D)J recombination and the generation of the T cell receptor and immunoglobulin molecules. Defects in LIG4 result in a variable syndrome of growth retardation, pancytopenia, combined immunodeficiency, cellular radiosensitivity, and developmental delay., Methods: We diagnosed a patient with LIG4 syndrome by radiosensitivity testing on peripheral blood cells, and established that two of her four healthy siblings carried the same compound heterozygous LIG4 mutations. An extensive analysis of the immune phenotype, cellular radiosensitivity, telomere length, and T and B cell antigen receptor repertoire was performed in all siblings., Results: In the three genotypically affected individuals, variable severities of radiosensitivity, alterations of T and B cell counts with an increased percentage of memory cells, and hypogammaglobulinemia, were noticed. Analysis of T and B cell antigen receptor repertoires demonstrated increased usage of alternative microhomology-mediated end-joining (MHMEJ) repair, leading to diminished N nucleotide addition and shorter CDR3 length. However, overall repertoire diversity was preserved., Conclusions: We demonstrate that LIG4 syndrome presents with high clinical variability even within the same family, and that distinctive immunologic abnormalities may be observed also in yet asymptomatic individuals.
- Published
- 2016
- Full Text
- View/download PDF
6. Identification of patients with RAG mutations previously diagnosed with common variable immunodeficiency disorders.
- Author
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Buchbinder D, Baker R, Lee YN, Ravell J, Zhang Y, McElwee J, Nugent D, Coonrod EM, Durtschi JD, Augustine NH, Voelkerding KV, Csomos K, Rosen L, Browne S, Walter JE, Notarangelo LD, Hill HR, and Kumánovics A
- Subjects
- Agammaglobulinemia diagnosis, Agammaglobulinemia etiology, Biopsy, Child, Preschool, Common Variable Immunodeficiency complications, Common Variable Immunodeficiency diagnosis, DNA Mutational Analysis, Fatal Outcome, Female, Humans, Immunohistochemistry, Lung Diseases, Interstitial diagnosis, Lung Diseases, Interstitial etiology, Lymphopenia diagnosis, Lymphopenia etiology, Tomography, X-Ray Computed, Young Adult, Common Variable Immunodeficiency genetics, Homeodomain Proteins genetics, Mutation
- Abstract
Purpose: Combined immunodeficiency (CID) presents a unique challenge to clinicians. Two patients presented with the prior clinical diagnosis of common variable immunodeficiency (CVID) disorder marked by an early age of presentation, opportunistic infections, and persistent lymphopenia. Due to the presence of atypical clinical features, next generation sequencing was applied documenting RAG deficiency in both patients., Methods: Two different genetic analysis techniques were applied in these patients including whole exome sequencing in one patient and the use of a gene panel designed to target genes known to cause primary immunodeficiency disorders (PIDD) in a second patient. Sanger dideoxy sequencing was used to confirm RAG1 mutations in both patients., Results: Two young adults with a history of recurrent bacterial sinopulmonary infections, viral infections, and autoimmune disease as well as progressive hypogammaglobulinemia, abnormal antibody responses, lymphopenia and a prior diagnosis of CVID disorder were evaluated. Compound heterozygous mutations in RAG1 (1) c256_257delAA, p86VfsX32 and (2) c1835A>G, pH612R were documented in one patient. Compound heterozygous mutations in RAG1 (1) c.1566G>T, p.W522C and (2) c.2689C>T, p. R897X) were documented in a second patient post-mortem following a fatal opportunistic infection., Conclusion: Astute clinical judgment in the evaluation of patients with PIDD is necessary. Atypical clinical findings such as early onset, granulomatous disease, or opportunistic infections should support the consideration of atypical forms of late onset CID secondary to RAG deficiency. Next generation sequencing approaches provide powerful tools in the investigation of these patients and may expedite definitive treatments.
- Published
- 2015
- Full Text
- View/download PDF
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