RESUMO
There is mounting evidence for the emerging role of gut microbiota (GM) and its metabolites in profoundly impacting allogenic hematopoietic stem cell transplantation (allo-HSCT) and its subsequent complications, mainly infections and graft versus host-disease (GvHD). The present study was performed in order to investigate changes in GM composition and fecal metabolic signature between transplant patients (n = 15) and healthy controls (n = 18). The intestinal microbiota was characterized by NGS and gas chromatography-mass spectrometry was employed to perform untargeted analysis of fecal metabolites. We found lower relative abundances of Actinobacteria, Firmicutes, and Bacteroidetes and a higher abundance of Proteobacteria phylum after allo-HSCT. Particularly, the GvHD microbiota was characterized by a lower relative abundance of the short-chain fatty acid-producing bacteria, namely, the Feacalibacterium, Akkermansia, and Veillonella genera and the Lachnospiraceae family, and an enrichment in multidrug-resistant bacteria belonging to Escherichia, Shigella, and Bacteroides. Moreover, network analysis showed that GvHD was linked to a higher number of positive interactions of Blautia and a significant mutual-exclusion rate of Citrobacter. The fecal metabolome was dominated by lipids in the transplant group when compared with the healthy individuals (p < 0.05). Overall, 76 metabolites were significantly altered within transplant recipients, of which 24 were selected as potential biomarkers. Furthermore, the most notable altered metabolic pathways included the TCA cycle; butanoate, propanoate, and pyruvate metabolisms; steroid biosynthesis; and glycolysis/gluconeogenesis. Specific biomarkers and altered metabolic pathways were correlated to GvHD onset. Our results showed significant shifts in gut microbiota structure and fecal metabolites characterizing allo-HSCT.
RESUMO
Since the elimination of indigenous transmission of malaria in Tunisia in 1979, almost all the cases observed are imported cases related to travel. We report a recent case of highly probable post-transfusion malaria (PTM) in a 27-year-old Tunisian who has never left Tunisia. He has been allografted and has received of the globular pellets and the platelet units along with his hospitalization. The evolution was marked by the appearance of a fever resistant to antibiotics 15 days later. On day 11 of fever, a thick drop (TD) and a blood smear (BS) showed trophozoites of Plasmodium falciparum with 20% parasitaemia. The evolution was favorable under quinine. The epidemiological survey concluded that among blood donors an African donor from Ivory Coast, in Tunisia for 2 months, had a TD, a BS, a rapid test and a nested PCR for P. falciparum species were negative, only the serology was positive by indirect immunofluorescence (1/20). Real-time PCR was positive for P. falciparum, and the diagnosis of highly probable PTM was retained. Blood transfusion is a transmission pathway for Plasmodium and contamination can occur with a very few parasites. As a result, the PTM must be considered for any unexplained fever arising in the aftermath of a blood transfusion that and establish strict prevention recommendations for PTM in our country.
Assuntos
Malária Falciparum/diagnóstico , Malária Falciparum/etiologia , Reação Transfusional/diagnóstico , Adulto , Antimaláricos/uso terapêutico , Humanos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/transmissão , Masculino , Plasmodium falciparum/isolamento & purificação , Reação Transfusional/tratamento farmacológico , Reação Transfusional/epidemiologia , Tunísia/epidemiologiaRESUMO
Fanconi anemia (FA) is a recessive chromosomal instability syndrome that is clinically characterized by multiple symptoms. Chromosome breakage hypersensitivity to alkylating agents is the gold standard test for FA diagnosis. In this study, we provide a detailed laboratory protocol for accurate assessment of FA diagnosis based on mitomycin C (MMC) test. Induced chromosomal breakage study was successful in 171 out of 205 aplastic anemia (AA) patients. According to the sensitivity of MMC at 50 ng/ml, 38 patients (22.22%) were diagnosed as affected and 132 patients (77.17%) as unaffected. Somatic mosaicism was suspected in an 11-year-old patient with a FA phenotype. Twenty-six siblings of FA patients were also evaluated and five of them (19.23%) were diagnosed as FA. From this study, a standard protocol for diagnosis of FA was developed. It is routinely used as a diagnostic test of FA in Tunisia.
Assuntos
Anemia Aplástica/diagnóstico , Antibióticos Antineoplásicos , Anemia de Fanconi/diagnóstico , Mitomicina , Adolescente , Adulto , Anemia Aplástica/epidemiologia , Anemia Aplástica/genética , Criança , Pré-Escolar , Quebra Cromossômica/efeitos dos fármacos , Fragilidade Cromossômica/efeitos dos fármacos , Consanguinidade , Diagnóstico Diferencial , Anemia de Fanconi/epidemiologia , Anemia de Fanconi/genética , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mosaicismo , Tunísia/epidemiologia , Adulto JovemRESUMO
FY antigens are candidate minor histocompatibility antigens relevant to renal allograft rejection, but no data have been reported about their role in graft-versus-host disease (GVHD) incidence after human leukocyte antigen (HLA)-identical siblings hematopoietic stem cell transplantation (HSCT). The aim of this study was to examine the effect of donor/recipient disparity at FY antigens on the incidence of GVHD in Tunisian patients receiving an HLA-identical HSCT. This work enrolled 105 Tunisian pairs of recipients and their HLA-identical sibling donors of HSCs. FY genotyping was performed with the polymerase chain reaction-sequence-specific primer method and donor/recipient disparity for these antigens was analyzed at two levels: incompatibility and nonidentity. The case-control analyses showed no significant correlation between FY disparity and the incidence of either acute or chronic GVHD. Sample size calculation showed that 572 cases and 1716 controls would be necessary to be able to detect a significant association with 80% power and two-sided type I error level of 5% (α=0.05). The lack of association in the studied cohort may be explained by the low immunogenicity of FY antigens in HSCT context, compared with other antigens such as HA-1 and CD31.
Assuntos
Sistema do Grupo Sanguíneo Duffy/imunologia , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas , Antígenos de Histocompatibilidade/imunologia , Leucócitos/imunologia , Receptores de Superfície Celular/imunologia , Irmãos , Doença Aguda , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: The aim of this study is to examine the effect of donor PECAM-1 alleles and haplotypes for the SNPs L98V, S536N, and R643G on the occurrence of GVHD in Tunisian recipients of HSCs. DESIGN AND METHODS: This study enrolled 102 patients and their 102 respective HLA-identical sibling donors of HSCs. The PECAM-1 SNPs genotyping assay was performed using sets of sequence specific primers (SSP-PCR). RESULTS: The single marker association analysis showed that the L98 allele, in a recessive genetic model, may be a potential risk factor only for acute GVHD (p=0.036, OR=2.580, 95% C.I. = 1.053-6.326). However, the haplotype analysis showed a lack of association between donor's PECAM-1 SNPs and GVHD incidence in recipient. CONCLUSION: The homozygosity state for donor PECAM-1L98 allele may be a significant risk factor for acute GVHD. This is probably due to its action on the function of donor leukocytes especially during the extravasation process.
Assuntos
Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Polimorfismo Genético/genética , Doadores de Tecidos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Genótipo , Haplótipos/genética , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Tunísia , Adulto JovemRESUMO
The CTLA-4 genetic variation, such as single nucleotide polymorphisms (SNPs) may be critical and can affect the functional activity of cells that initiate the graft-versus-host disease (GVHD) effects. The aim of this study is to examine the effect of donor CTLA-4 alleles and haplotypes for the -318C>T and the 49A>G polymorphisms on the occurrence of GVHD in Tunisians recipients of HSCs. A total of 112 patients and their 112 respective sibling donors of HSCs were enrolled in this study. All patients had either grades 0-I or grades II-IV acute GVHD, or chronic GVHD. The SNPs genotyping assay was performed using sets of sequence specific primers (SSP-PCR). The single marker association analysis showed that the 49G allele, in a genetic recessive model, may be a potential risk factor only for the chronic GVHD (p = 0.032, odds ratio [OR] = 2.58, 95% confidence interval = 1.05-6.32). The haplotypes analyses showed that the CTLA-4 -318C49G nucleotide combination is significantly associated with the incidence of chronic GVHD (p = 0.043, χ² = 3.27). Donor CTLA-4 -318C49G haplotype may be a significant risk factor for developing chronic GVHD after allo-stem cell transplantation. We suppose that donor T cells expressing this haplotype in a homozygous state have higher proliferation than those expressing other haplotypes, especially after recognition of the recipient's minor histocompatibility antigens.
Assuntos
Antígenos CD/genética , Frequência do Gene/imunologia , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/imunologia , Haplótipos/imunologia , Polimorfismo de Nucleotídeo Único/imunologia , Adolescente , Adulto , Alelos , Antígenos CD/imunologia , Antígeno CTLA-4 , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença , Genótipo , Doença Enxerto-Hospedeiro/etiologia , Antígenos HLA/genética , Antígenos HLA/imunologia , Haplótipos/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/fisiopatologia , Transtornos Linfoproliferativos/terapia , Masculino , Pessoa de Meia-Idade , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Menor/imunologia , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Irmãos , Doadores de Tecidos , Transplante Homólogo , Tunísia , Adulto JovemRESUMO
This paper presents the results of a cytogenetic analysis in 139 Tunisian patients with de novo acute myeloid leukemia (AML), including 27 children aged 1-15 years and 112 adults. Mean age was 32 (range 1-75) and the M/F ratio was 1.43. Of our patients, 45% had apparently normal karyotypes. Acquired chromosome aberrations were found in 77 (55% ) patients. t(8;21) was identified in 27 patients (19%); t(15;17) in 13 patients (9%); deletion 7q or monosomy 7 in seven patients (5%); +8 in seven patients (5%); abnormal 16 in four patients (3%); 11q23 rearrangements in two patients (2%) and del(5q), in one patient (1%). The remaining 16 patients had miscellaneous clonal abnormalities. Specific translocations associated with the FAB type were found: t(8;21) with AML2 and t(15;17) with AML3. We concluded that our study in a Tunisian population confirmed the relation between some specific abnormalities and the FAB classification. We found a higher incidence for t(8;21) than usually described.