Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 46
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Clin Immunol ; 210: 108309, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31751612

RESUMO

Mutations affecting the non-canonical pathway of NF-κB were recently identified to underlie a form of common variable immunodeficiency strongly associated with autoimmunity. Although intrinsic B-cell abnormalities explain most of the humoral defects of this disease, detailed data on the impact of NFKB2 on follicular helper (Tfh) and regulatory (Tregs) T cells are scarce. Here, we show that Tfh, CXCR5+, and CXCR5- Treg cell subsets were significantly reduced in patients heterozygous for a truncating mutation of NFKB2. Plasma CXCL13 levels were reduced, underlining an important role for NFKB2 in regulating the germinal center (GC) response. Proinflammatory IFNγ, IL-17 and IL-10 cytokine production by CD4 T cells was lower in the mutated patients, but the production of IL-4 and IL-21 was not altered. Taken together, our findings show that NFKB2 influences the quality and efficiency of human GC reaction, by affecting not only the B cells but also GC-relevant T cell subsets.

2.
Front Immunol ; 10: 2471, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31736942

RESUMO

Patients with severe combined immunodeficiency (SCID) exhibit T lymphopenia and profound impairments in cellular and humoral immunity. IL-7 receptor α (IL-7Rα) deficiency is a rare form of SCID that usually presents in the first months of life with severe and opportunistic infections, failure to thrive and high risk of mortality unless treated. Here, we reported an atypical and delayed onset of IL7Rα-SCID in a 15-month-old girl presenting with thrombocytopenia. Immunological investigations showed a normal lymphocyte count with isolated CD4-penia, absence of naïve T cells, marked hypergammaglobulinemia, and maternal T cell engraftment. Targeted next generation sequencing (NGS) revealed two novel compound heterozygous mutations in the IL-7Rα gene: c.160T>C (p.S54P) and c.245G>T (p.C82F). The atypical onset and the unusual immunological phenotype expressed by our patient highlights the diagnostic challenge in the field of primary immunodeficiencies (PID) and in particular in SCID patients where prompt diagnosis and therapy greatly affects survival.

3.
J Exp Med ; 216(12): 2778-2799, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31601675

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to inadequate restraint of overactivated immune cells and is associated with a variable clinical spectrum having overlap with more common pathophysiologies. HLH is difficult to diagnose and can be part of inflammatory syndromes. Here, we identify a novel hematological/autoinflammatory condition (NOCARH syndrome) in four unrelated patients with superimposable features, including neonatal-onset cytopenia with dyshematopoiesis, autoinflammation, rash, and HLH. Patients shared the same de novo CDC42 mutation (Chr1:22417990C>T, p.R186C) and altered hematopoietic compartment, immune dysregulation, and inflammation. CDC42 mutations had been associated with syndromic neurodevelopmental disorders. In vitro and in vivo assays documented unique effects of p.R186C on CDC42 localization and function, correlating with the distinctiveness of the trait. Emapalumab was critical to the survival of one patient, who underwent successful bone marrow transplantation. Early recognition of the disorder and establishment of treatment followed by bone marrow transplant are important to survival.

5.
Front Immunol ; 10: 447, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949166

RESUMO

The thymus plays a fundamental role in establishing and maintaining central and peripheral tolerance and defects in thymic architecture or AIRE expression result in the development of autoreactive lymphocytes. Patients with partial DiGeorge Syndrome (pDGS) and Down Syndrome (DS) present alterations in size and architecture of the thymus and higher risk to develop autoimmunity. We sought to evaluate thymic architecture and thymocyte development in DGS and DS patients and to determine the extent to which thymic defects result in immune dysregulation and T cell homeostasis perturbation in these patients. Thymi from pediatric patients and age-matched controls were obtained to evaluate cortex and medullary compartments, AIRE expression and thymocyte development. In the same patients we also characterized immunophenotype of peripheral T cells. Phenotypic and functional characterization of thymic and peripheral regulatory T (Treg) cells was finally assessed. Histologic analysis revealed peculiar alterations in thymic medulla size and maturation in DGS and DS patients. Perturbed distribution of thymocytes and altered thymic output was also observed. DGS patients showed lower mature CD4+ and CD8+ T cell frequency, associated with reduced proportion and function of Tregs both in thymus and peripheral blood. DS patients showed increased frequency of single positive (SP) thymocytes and thymic Treg cells. However, Tregs isolated both from thymus and peripheral blood of DS patients showed reduced suppressive ability. Our results provide novel insights on thymic defects associated with DGS and DS and their impact on peripheral immune dysregulation. Indeed, thymic abnormalities and defect in thymocyte development, in particular in Treg cell number and function could contribute in the pathogenesis of the immunodysregulation present in pDGS and in DS patients.

6.
Front Immunol ; 10: 316, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31031743

RESUMO

Background: Primary Immunodeficiencies (PIDs) are a heterogeneous group of genetic immune disorders. While some PIDs can manifest with more than one phenotype, signs, and symptoms of various PIDs overlap considerably. Recently, novel defects in immune-related genes and additional variants in previously reported genes responsible for PIDs have been successfully identified by Next Generation Sequencing (NGS), allowing the recognition of a broad spectrum of disorders. Objective: To evaluate the strength and weakness of targeted NGS sequencing using custom-made Ion Torrent and Haloplex (Agilent) panels for diagnostics and research purposes. Methods: Five different panels including known and candidate genes were used to screen 105 patients with distinct PID features divided in three main PID categories: T cell defects, Humoral defects and Other PIDs. The Ion Torrent sequencing platform was used in 73 patients. Among these, 18 selected patients without a molecular diagnosis and 32 additional patients were analyzed by Haloplex enrichment technology. Results: The complementary use of the two custom-made targeted sequencing approaches allowed the identification of causative variants in 28.6% (n = 30) of patients. Twenty-two out of 73 (34.6%) patients were diagnosed by Ion Torrent. In this group 20 were included in the SCID/CID category. Eight out of 50 (16%) patients were diagnosed by Haloplex workflow. Ion Torrent method was highly successful for those cases with well-defined phenotypes for immunological and clinical presentation. The Haloplex approach was able to diagnose 4 SCID/CID patients and 4 additional patients with complex and extended phenotypes, embracing all three PID categories in which this approach was more efficient. Both technologies showed good gene coverage. Conclusions: NGS technology represents a powerful approach in the complex field of rare disorders but its different application should be weighted. A relatively small NGS target panel can be successfully applied for a robust diagnostic suspicion, while when the spectrum of clinical phenotypes overlaps more than one PID an in-depth NGS analysis is required, including also whole exome/genome sequencing to identify the causative gene.

7.
J Allergy Clin Immunol Pract ; 7(7): 2369-2376, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30922987

RESUMO

BACKGROUND: Patients with 22q11.2 deletion syndrome (22q11.2DS) may develop severe thrombocytopenic purpura and hemolytic anemia. There are no reliable predictors for the development of hematologic autoimmunity (HA) in these patients. OBJECTIVE: To describe the peculiar B and T subpopulation defects in patients with 22q11DS who have developed HA and test if these defects precede the development of HA. METHODS: We performed a case-control multicenter study. Patients with HA were compared with a control population of 22q11.2DS without HA (non-HA). A complete immunological evaluation was performed at diagnosis and at the last follow-up including extensive T and B phenotypes. RESULTS: Immunophenotype at the last follow-up was available in 23 HA and 45 non-HA patients. HA patients had significantly decreased percentage of naïve CD4+ cells (26.8% vs 43.2%, P = .003) and recent thymic emigrants (48.6% vs 80.5%, P = .046); decreased class-switched B cells (2.0% vs 5.9%, P = .04) and increased naive B cells (83.5% vs 71.4%, P = .02); increased CD16+/56+ both in absolute number (312 vs 199, P = .009) and percentage (20.0% vs 13.0%, P = .03). Immunophenotype was performed in 36 patients (11 HA and 25 non-HA) at diagnosis. Odds ratio (OR) of immune cytopenia were estimated for both CD4 naïve ≤30% (OR 14.0, P = .002) and switched memory B cells ≤2% (OR 44.0, P = .01). The estimated survival curves reached statistical significance, respectively, P = .0001 and P = .002. CONCLUSIONS: Among patients with 22q11.2DS, those with HA have characteristic lymphocyte anomalies that appear considerably before HA onset. Systematic immunophenotyping of patients with 22q11.2DS at diagnosis is advisable for early identification of patients at risk for this severe complication.

8.
Front Immunol ; 10: 130, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30837984

RESUMO

We described for the first time a female patient with the simultaneous presence of two homozygous mutations in MYD88 and CARD9 genes presenting with pyogenic bacterial infections, elevated IgE, and persistent EBV viremia. In addition to defective TLR/IL1R-signaling, we described novel functional alterations into the myeloid compartment. In particular, we demonstrated a defective production of reactive oxygen species exclusively in monocytes upon E. coli stimulation, the inability of immature mono-derived DCs (iDCs) to differentiate into mature DCs (mDCs) and the incapacity of mono-derived macrophages (MDMs) to resolve BCG infection in vitro. Our data do not provide any evidence for digenic inheritance in our patient, but rather for the association of two monogenic disorders. This case illustrates the importance of using next generation sequencing (NGS) to determine the most accurate and early diagnosis in atypical clinical and immunological phenotypes, and with particular concern in consanguineous families. Indeed, besides the increased susceptibility to recurrent invasive pyogenic bacterial infections due to MYD88 deficiency, the identification of CARD9 mutations underline the risk of developing invasive fungal infections emphasizing the careful monitoring for the occurrence of fungal infection and the opportunity of long-term antifungal prophylaxis.

9.
Clin Immunol ; 201: 30-34, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30776520

RESUMO

Severe combined immunodeficiencies (SCID) comprise a group of genetic diseases characterized by abrogated development of T lymphocytes. In some case reports of atypical SCID patients elevated proportions of γδ T lymphocytes have been reported. However, it is unknown whether these γδ T cells modulate or reflect the patient's clinical phenotype. We investigated the frequency of elevated γδ T cell proportions and associations with clinical disease manifestations in a cohort of 76 atypical SCID patients. Increased proportions of γδ T lymphocytes were present in approximately 60% of these patients. Furthermore, we identified positive correlations between elevated proportions of γδ T cells and the occurrence of CMV infections and autoimmune cytopenias. We discuss that CMV infections might trigger an expansion of γδ T lymphocytes, which could drive the development of autoimmune cytopenias. We advocate that atypical SCID patients should be screened for elevated proportions of γδ T lymphocytes, CMV infection and autoimmune cytopenias.

10.
Stem Cells ; 37(3): 332-344, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30566254

RESUMO

Kit is a growth factor receptor that regulates proliferation and/or survival of many embryonic and postnatal stem cell types. When mutated, it can induce malignant transformation of the host cells. To dissect the Kit role in the control of ESC pluripotency, we studied its expression during early mouse embryogenesis and during the process of ESC derivation from inner cell mass (ICM) cells. We followed the in vitro development of early mouse embryos obtained from transgenic mice carrying Kit promoter regions fused to EGFP (Kit-EGFP) and found that they initiate EGFP expression at morula stage. EGFP expression is then maintained in the blastocyst, within the ICM, and its levels increase when cultured in the presence of MAPK and GSK3ß inhibitors (2i) plus LIF compared with the LIF-only condition. Kit-EGFP ESCs showed nonhomogeneous EGFP expression pattern when cultured in LIF condition, but they upregulated EGFP expression, as well as that of Sox2, Nanog, Prdm14, when shifted to 2i-LIF culture. Similarly, primordial germ cells (PGCs) in the process of embryonic germ cell (EGC) conversion showed enhanced EGFP expression in 2i-LIF. Kit expression was affected by manipulating Sox2 levels in ESCs. Chromatin immunoprecipitation experiments confirmed that Sox2 binds Kit regulatory regions containing Sox2 consensus sequences. Finally, Kit constitutive activation induced by the D814Y mutation increased ESC proliferation and cloning efficiency in vitro and in teratoma assays in vivo. Our results identify Kit as a pluripotency-responsive gene and suggest a role for Kit in the regulation of ESC proliferation. Stem Cells 2019;37:332-344.

11.
Eur J Pediatr ; 2018 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-30269248

RESUMO

Selective IgA deficiency is defined as absolute or partial when serum IgA level is < 7 mg/dl or 2 SD below normal for age, respectively. Few data are available on partial selective IgA deficiency, as probably most children with low serum IgA are seldom referred to a specialist clinic in common pediatric practice. The aim of our study was to better define the profile of both symptomatic forms and their clinical outcome in a pediatric immunology setting. Thus, clinical and immunological data from 103 symptomatic patients with selective IgA deficiency (53 absolute and 50 partial), 4-18 years of age, were collected at diagnosis and 80 patients (44 absolute and 36 partial) were monitored for a mean period of 5 years. Also, the prevalence of TNFRSF13B mutations has been assessed in 56 patients. The most common clinical features were infections (86/103; 83%), allergy (39/103; 38%), and autoimmunity (13/103; 13%). No significative differences were observed between absolute and partial selective IgA deficiency patients. However, a significative difference in the rate of IgA normalization between partial and absolute selective IgA deficiency patients (33 vs 9%, p = 0.01) was detected. Furthermore, a lower incidence of infections was associated to a normalization reversal compared to a final absolute or partial defect status (12 vs 53 and 64% respectively, p < 0.01). CONCLUSIONS: Regardless of a diagnosis of absolute or partial defect, monitoring of symptomatic patients with selective IgA deficiency is recommended overtime for prompt identification and treatment of associated diseases. Further, diagnostic workup protocols should be revisited in children with IgA deficiency. What is Known: ● Selective IgA Deficiency is the most common primary immunodeficiency and is usually asymptomatic. ● Symptomatic pediatric patients with selective IgA deficiency mostly suffer with respiratory and gastrointestinal infections. What is New: ● Symptomatic children with partial IgA defect may have similar clinical, immunological, and genetic features than symptomatic children with absolute IgA deficiency. ● Symptomatic children with partial IgA deficiency deserve accurate monitoring for associated diseases as per children with absolute IgA deficiency.

12.
Artigo em Inglês | MEDLINE | ID: mdl-30044346

RESUMO

BACKGROUND: Jagunal homolog 1 (JAGN1) gene was identified as a novel responsible for severe congenital neutropenia. The protein encoded by this gene is required for neutrophil differentiation, survival and function in microbial activity. JAGN1-deficient human neutrophils are characterized by alterations in trafficking within the endoplasmic reticulum and golgi compartments because of ultrastructural defects in endoplasmic reticulum and susceptibility to apoptosis. OBSERVATIONS: We report a patient exhibiting an intermittent neutropenia, for which a next-generation sequencing revealed a homozygous mutation in the JAGN1 gene. CONCLUSIONS: The patient extends the clinical variability associated to JAGN1 mutations, and this case highlights the importance of genetic investigations in patients with suspected neutropenia.

13.
Mol Genet Genomic Med ; 6(5): 713-721, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30032486

RESUMO

BACKGROUND: Mutations in the Janus Kinase 3 (JAK3) gene cause an autosomal recessive form of severe combined immunodeficiency (SCID) usually characterized by the absence of both T and NK cells, but preserved numbers of B lymphocytes (T-B+NK-SCID). The detection of larger (>100 bp) genomic duplications or deletions can be more difficult to be detected by PCR-based methods or standard NGS protocols, and a broad range of mutation detection techniques are necessary. METHODS: We report four unrelated Italian patients (two females and two males) with SCID phenotype. Protein expression, functional studies, molecular analysis by standard methods and NGS, and transcripts studies were performed to obtain a definitive diagnosis. RESULTS: Here, we describe four JAK3-deficient patients from four unrelated families. The first patient is homozygous for the known c.1951 C>T mutation causing the amino acidic change p.R651W. The other two patients, originating from the same small Italian town, resulted compound heterozygotes for the same g.15410_16542del deletion and two different novel mutations, g.13319_13321delTTC and c.933T>G (p.F292V), respectively. The fourth patient was compound heterozygous for the novel mutations p.V599G and p.W709R. Defective STAT5 phosphorylation after IL2 or IL15 stimulation corroborated the mutation pathogenicity. Concerning g.15410_16542del mutation, probably due to an unequal homologous recombination between Alu elements of JAK3 gene, microsatellites analysis revealed that both unrelated Pt2 and Pt3 and their carrier family members shared the same haplotype. These data support the hypothesis of a founder effect for the g.15410_16542del mutation that might have inherited in both unrelated families from the same ancient progenitor. CONCLUSION: Different molecular techniques are still required to obtain a definitive diagnosis of AR-SCID particularly in all cases in which a monoallelic mutation is found by standard mutation scanning methods.

14.
Clin Immunol ; 193: 52-59, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29410324

RESUMO

Chronic granulomatous disease (CGD) is a phagocytic disorder characterized by a defective production of reactive oxygen species (ROSs). Although infections and granuloma formation are the most common manifestations in CGD patients, a significant number of patients experienced autoimmunity and inflammatory diseases suggesting that adaptive immune abnormalities might be involved. Here we investigated T-cell compartment and showed that CGD patients had a skewed TCRV-beta distribution in CD8+ T cells, particularly in older patients, and a reduced proliferative responses toward mitogens compared to healthy donors (HD). Afterwards we studied the role of gp91phox protein in causing these alterations and demonstrated that human T cells do not express gp91phox and TCR-stimulated ROS generation is gp91phox-NADPH oxidase independent. Finally, we proved that the NADPH oxidase is not active in the T cell compartment even when forcing gp91phox expression transducing T cells from X-CGD and HD with a SIN lentiviral vector (LVV) encoding the gp91phox cDNA.

16.
Immunol Lett ; 190: 185-193, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28826739

RESUMO

HIV-1-infected patients failing to recover CD4+ T-cell count despite HAART (immunological non-responders, NRs), are at increased risk of disease progression and death. To better understand the NR status, we performed a comprehensive assessment of NK cells in NR patients as compared to immunologic responders. NRs exhibited an accumulation of CD56bright NK cells inversely correlated with CD4+ counts. Both CD56bright and CD56dim NK cells of NRs displayed unimpaired degranulation ability, but poorly responded to cytokine stimulation in terms of NKp44 up-regulation and IFN-γ production that may explain the susceptibility of NRs to infections and tumors. Notably, CD56bright NK cells from NRs showed higher cytotoxicity against autologous activated CD4+ T cells. Moreover, NRs had reduced Treg cell counts that showed an inverse correlation with autoreactive CD56bright cells. These data suggest that accumulation of CD56bright NK cells, possibly linked to decreased homeostatic control by Tregs, contributes to poor immune reconstitution in NRs.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Células Matadoras Naturais/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Terapia Antirretroviral de Alta Atividade , Autoantígenos , Autoimunidade , Antígeno CD56/metabolismo , Resistência a Medicamentos , Feminino , Infecções por HIV/tratamento farmacológico , Homeostase , Humanos , Interferon gama/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade
17.
Front Pediatr ; 5: 95, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28512628

RESUMO

WHIM syndrome is a condition in which affected persons have chronic peripheral neutropenia, lymphopenia, abnormal susceptibility to human papilloma virus infection, and myelokathexis. Myelokathexis refers to the retention of mature neutrophils in the bone marrow (BM), which accounts for degenerative changes and hypersegmentation. Most patients present heterozygous autosomal dominant mutations of the gene encoding CXCR4. Consequently, aberrant CXCL12/CXCR4 signaling impairs the receptor downregulation causing hyperactivation (gain-of-function) that affects BM homing for myelopoiesis and lymphopoiesis and the release of neutrophils in the bloodstream. We report the case of a 26-year-old female with severe foot and hand cutaneous warts since childhood, recalcitrant genital condylomatas, bacterial infections, and intraepithelial cervical neoplasia. Laboratory tests revealed severe B lymphopenia and HPV high and low risk types. HIV testing was negative. Not only CXCR4 but also GATA2, NEMO, and CD40L gene mutations were excluded. BM smears revealed, in the presence of a normal cellularity, hyperplasia of myeloid cells (MPO positive) and karyorrhexis, especially in neutrophils and eosinophils. Of note, neutrophils with altered lobation of nuclei connected by long thin chromatin filaments were observed. Our patient presented a clinical and histological picture reminiscent of WHIM in the presence of normal peripheral neutrophil counts and wild-type CXCR4 gene. Although the BM did not reveal a classical pattern of myelokathexis, the observation of consistent signs of neutrophil dysplasia has fuelled the hypothesis of a novel WHIM variant or a novel immunodeficiency. We speculate that abnormalities that affect CXCR4/CXCL12 pair, including GRK levels or activity, might be responsible for this WHIM-like disorder.

18.
Front Immunol ; 8: 1893, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29312354

RESUMO

Monogenic defects in genes related to primary immunodeficiencies can be responsible for inflammatory bowel disease (IBD). Mutations in the X-linked inhibitor of apoptosis (XIAP) gene have been described in several patients suffering from IBD and, in particular, with very early-onset inflammatory bowel disease (VEOIBD) features. We report a VEOIBD child with a novel XIAP gene mutation characterized by a complicated disease course, which is unresponsive to several medical treatment options. A next-generation sequencing was performed and revealed a de novo hemizygous mutation in XIAP gene: c.565T>C p.L189P. After mutation discovery, we investigated the XIAP protein expression and nucleotide-binding oligomerization domain protein 2 (NOD2) signaling by western blotting. Flow-cytometry was used to analyze intracellular protein expression in different cell subsets and T cell apoptosis. We observed reduced protein expression in lymphocytes, granulocytes, monocytes, an Epstein-Barr virus-immortalized B cell line as well as increased apoptosis, and impairment in NOD2 signaling. The child was successfully treated with HLA-haploidentical hemapoietic stem cells transplant, acquired from his mother, after ex vivo elimination of α/ß T cells and CD19 B cells. One year after the transplant, we repeated the analysis to appreciate the changes in his impairments. The recovery of XIAP protein expression, function, and normalization of apoptosis were observed. Our report emphasizes the important role of genetic analysis in the diagnosis of VEOIBD, illustrates the complete immunological and gastrointestinal recovery after transplant, and shows one of the few successful transplant cases of XIAP patients.

20.
J Allergy Clin Immunol ; 139(4): 1302-1310.e4, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27658761

RESUMO

BACKGROUND: Absent T-cell immunity resulting in life-threatening infections provides a clear rationale for hematopoetic stem cell transplantation (HSCT) in patients with severe combined immunodeficiency (SCID). Combined immunodeficiencies (CIDs) and "atypical" SCID show reduced, not absent T-cell immunity. If associated with infections or autoimmunity, they represent profound combined immunodeficiency (P-CID), for which outcome data are insufficient for unambiguous early transplant decisions. OBJECTIVES: We sought to compare natural histories of severity-matched patients with/without subsequent transplantation and to determine whether immunologic and/or clinical parameters may be predictive for outcome. METHODS: In this prospective and retrospective observational study, we recruited nontransplanted patients with P-CID aged 1 to 16 years to compare natural histories of severity-matched patients with/without subsequent transplantation and to determine whether immunologic and/or clinical parameters may be predictive for outcome. RESULTS: A total of 51 patients were recruited (median age, 9.6 years). Thirteen of 51 had a genetic diagnosis of "atypical" SCID and 14 of 51 of CID. About half of the patients had less than 10% naive T cells, reduced/absent T-cell proliferation, and at least 1 significant clinical event/year, demonstrating their profound immunodeficiency. Nineteen patients (37%) underwent transplantation within 1 year of enrolment, and 5 of 51 patients died. Analysis of the HSCT decisions revealed the anticipated heterogeneity, favoring an ongoing prospective matched-pair analysis of patients with similar disease severity with or without transplantation. Importantly, so far neither the genetic diagnosis nor basic measurements of T-cell immunity were good predictors of disease evolution. CONCLUSIONS: The P-CID study for the first time characterizes a group of patients with nontypical SCID T-cell deficiencies from a therapeutic perspective. Because genetic and basic T-cell parameters provide limited guidance, prospective data from this study will be a helpful resource for guiding the difficult HSCT decisions in patients with P-CID.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/patologia , Imunodeficiência Combinada Severa/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Projetos de Pesquisa
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA