Immunological profile of Fanconi anemia: A multicentric retrospective analysis of 61 patients

Korthof, Elisabeth T.; Svahn, Johanna; Latour, Régis Peffault de; Terranova, Paola; Moins‐Teisserenc, Hélène; Socié, Gèrard; Soulier, Jean; Kok, Marleen; Bredius, Robbert G. M.; Tol, Maarten van; Zijde, E.C.M. Jol-van der; Pistorio, Angela; Corsolini, Fabio; Parodi, Alessia; Battaglia, Florinda; Pistoia, Vito; Dufour, Carlo; Cappelli, Enrico

doi:10.1002/ajh.23435

Cited by 41 publications

(35 citation statements)

References 26 publications

(36 reference statements)

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“…Studies by others have reported normal or decreased numbers of T cells in FA, while B cells were generally decreased 7,15,16 . We found below normal numbers of absolute lymphocyte counts in one-third of children and adults with FA, but the adults as a group had lower ALC than normal relatives or children with FA.…”

Section: Discussionmentioning

confidence: 79%

“…Prior publications suggested that immunoglobulins were decreased 15 or normal 10,16 in patients with FA, but did not separate children and adults or adjust for other variables. In our study, most children with FA had normal levels of immunoglobulins, while half of the adults had decreased levels.…”

Section: Discussionmentioning

confidence: 99%

“…The number of recent comprehensive immunological studies is small and findings inconsistent 13–16 . The most frequent immune abnormalities reported are low B and NK cell numbers or decreased NK cell activity 4,15,16 . Myers et al found normal immunoglobulin IgG in children with FA 16 , while Kortoff et al studied patients with FA with severe BMF and reported low serum IgG and IgM, and high serum interleukin (IL)-6 and transforming growth factor (TGF)-β, and low soluble CD40 ligand 15 .…”

Section: Introductionmentioning

confidence: 99%

“…The most frequent immune abnormalities reported are low B and NK cell numbers or decreased NK cell activity 4,15,16 . Myers et al found normal immunoglobulin IgG in children with FA 16 , while Kortoff et al studied patients with FA with severe BMF and reported low serum IgG and IgM, and high serum interleukin (IL)-6 and transforming growth factor (TGF)-β, and low soluble CD40 ligand 15 . Justo et al described elevated plasma levels of IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ, but normal TGF-β in a subset of patients with FA 13 .…”

Section: Introductionmentioning

confidence: 99%

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Immune status of patients with inherited bone marrow failure syndromes

et al. 2015

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Immune function abnormalities have been reported in patients with Fanconi anemia (FA), dyskeratosis congenita (DC) and, rarely, in Shwachman-Diamond syndrome (SDS) and Diamond-Blackfan anemia (DBA), but large systematic studies are lacking. We assessed immunological parameters in 118 patients with these syndromes and 202 unaffected relatives. We compared results in patients with reference values, and with values in relatives after adjusting for age, sex, corticosteroid-treatment and severe bone marrow failure (BMF). Adult patients (≥18 years) with FA had significantly lower immunoglobulins (IgG, IgA and IgM), total lymphocytes and CD4 T-cells than reference values or adult relatives (p<0.001); children with FA had normal values. Both children and adults with FA had lower B- and NK-cells (p<0.01) than relatives or reference values. Patients with DC had essentially normal immunoglobulins but lower total lymphocytes than reference values or relatives, and lower T-, B- and NK-cells; these changes were more marked in children than adults (p<0.01). Most patients with DBA and SDS had normal immunoglobulins and lymphocytes. Lymphoproliferative responses, serum cytokine levels, including TNF-α and IFN-γ, and cytokine levels in supernatants from phytohemagglutinin-stimulated cultures were similar across patient groups and relatives. Only patients with severe BMF, particularly those with FA and DC, had higher serum G-CSF and Flt3-ligand and lower RANTES levels compared with all other groups or relatives (p<0.05). Overall, immune function abnormalities were seen mainly in adult patients with FA, which likely reflects their disease-related progression, and in children with DC, which may be a feature of early-onset severe disease phenotype.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immune status of patients with inherited bone marrow failure syndromes

et al. 2015

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“…18 More recent studies, using primary samples, linked immunological alterations to cell apoptosis and tissue inflammation in FA patients. 19,20 However, mechanisms responsible for these described immune deficiencies remain poorly understood. In the present study, we show for the first time that the function of Tregs that is deficient for Fanca or Fancd2 is decreased, a finding that may contribute mechanistically to clinical immune deficiency in FA patients.…”

Section: Introductionmentioning

confidence: 99%

Deletion of Fanca or Fancd2 dysregulates Treg in mice

Erden

Wilson

et al. 2014

Blood

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Genetic screening of children with marrow failure. The role of primary Immunodeficiencies

et al. 2021

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The differential diagnosis of marrow failure (MF) is crucial in the diagnostic work-up, since genetic forms require specific care. We retrospectively studied all patients with single/multi-lineage MF evaluated in a single-center to identify the type and incidence of underlying molecular defects. The diepoxybutane test was used to screen Fanconi Anemia. Other congenital MFs have been searched using Sanger and/or Next Generation Sequencing analysis, depending on the available tools over the years. Between 2009-2019, 97 patients (aged 0-32 years-median 5) with singlelineage (29%) or multilineage (68%) MF were evaluated. Fifty-three (54%) and 28 (29%) were diagnosed with acquired and congenital MF, respectively. The remaining 16 (17%), with trilinear (n=9) and monolinear (n=7) MF, were found to have an underlying primary immunodeficiency (PID) and showed clinical and biochemical signs of immune-dysregulation in 10/16 (62%) and in 14/16 (87%) of cases, respectively. Clinical signs were also found in 22/53 (41%) and 8/28 (28%) patients with idiopathic and classical cMF, respectively. Eight out of 16 PIDs patients were successfully transplanted, four received immunosuppression, two did not require treatment, and the remaining two died. We show that patients with single/multilineage MF may have underlying PIDs in a considerable number of cases and that MF may represent a relevant clinical sign in patients with PIDs, thus widening their clinical phenotype. An accurate immunological work-up should be performed in all patients with MF, and PID-related genes should be considered when screening MF in order to identify disorders that may receive targeted treatments and/or appropriate conditioning regimens before transplant. | INTRODUCTIONAn accurate diagnostic work-up of children with bone marrow failure (MF) is a critical step for clinical management of the disease. In particular, the differential diagnosis between constitutional and acquired forms is a key way to identify specific treatment strategies 1-3 and a M Miano and A. Grossi equally contributed to this work. This study was approved by local ethical committee. Patients' consent form was obtained. No material from other sources was used. Data are

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Immunological profile of Fanconi anemia: A multicentric retrospective analysis of 61 patients

Cited by 41 publications

References 26 publications

Immune status of patients with inherited bone marrow failure syndromes

Immune status of patients with inherited bone marrow failure syndromes

Deletion of Fanca or Fancd2 dysregulates Treg in mice

Genetic screening of children with marrow failure. The role of primary Immunodeficiencies

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