1/39. Neutrophil antigen 5b is carried by a protein, migrating from 70 to 95 kDa, and may be involved in neonatal alloimmune neutropenia.BACKGROUND: Neutrophil antigen 5b has been described as involved in transfusion reactions and not in neonatal alloimmune neutropenia. CASE REPORT: Anti-5b was found in the serum of a mother of a persistently neutropenic newborn, who had several bacterial infections. The neutropenia responded to treatment with recombinant human granulocyte-colony-stimulating factor. immunoprecipitation experiments performed with this and three other 5b antisera identified a protein, migrating from 70 to 95 kDa, as carrier of 5b. The observed pattern of migration may point to heavy glycosylation of this protein. RESULTS: Six 5b-negative donors were identified among 54 screened white donors, for a 5b gene frequency of 0.66. CONCLUSION: Alloimmunization to 5b in pregnancy is rare. In the patients with neonatal neutropenia analyzed in the last decade, this was the first case discovered.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
2/39. Neonatal alloimmune neutropenia in premature monozygous twins.Alloimmune neonatal neutropenia (ANN) is an uncommon but potentially life-threatening disorder of the neonate and young infant. Hematologically, the mother's peripheral neutrophil count is normal. However, the passive transfer of maternal immunoglobulin g neutrophil-specific antibodies and the subsequent sensitization of fetal neutrophils can result in severe neutropenia in the neonate. Generally, ANN is a self-limiting condition, but with severe bacterial infection, mortality can be high. We present the clinical features of monozygous twins delivered at 33 weeks' postconception with this condition. This case report is unique in that it occurred in twins born prematurely and was attributable to antibodies against 2 neutrophil-specific antigens, NA1 and NB1. A brief review of the diagnosis, management, and treatment of ANN is presented.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
3/39. Large granular lymphocyte leukemia and its association with oral neutropenic ulcerations: a case report.Large granular lymphocyte leukemia is a rare chronic indolent disorder commonly associated with severe neutropenia. The pathogenesis of the neutropenia is unclear. A case is presented of a 74-year-old man who had recurrent oral ulcerations for over a year before a diagnosis was made. These recurrent oral ulcers cleared with treatment and have not returned. The differential diagnosis of persistent oral ulcerations includes trauma; viral, fungal, and bacterial infections; systemic disease; or various malignant conditions. The oral ulcers in this man were likely infectious in nature and related to the severe chronic neutropenia. This case serves to illustrate the potentially complex nature of oral ulcers.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
4/39. Neutrophil-specific granule deficiency: homozygous recessive inheritance of a frameshift mutation in the gene encoding transcription factor CCAAT/enhancer binding protein--epsilon.Neutrophil-specific granule deficiency (SGD) is a rare congenital disorder. The neutrophils of individuals with SGD display atypical bi-lobed nuclei, lack expression of all secondary and tertiary granule proteins, and possess defects in chemotaxis, disaggregation, receptor up-regulation, and bactericidal activity, resulting in frequent and severe bacterial infections. Previously, a homozygous mutation in the CCAAT/enhancer binding protein-epsilon (C/EBPepsilon) gene was reported for one case of SGD. To substantiate the role of C/EBPepsilon in the development of SGD and elucidate its mechanism of inheritance, the mutational status of the gene was determined in a second individual. An A-nucleotide insertion in the coding region of the C/EBPepsilon gene was detected. This mutation completely abolished the predicted translation of all C/EBPepsilon isoforms. Microsatellite and nucleotide sequence analyses of the C/EBPepsilon locus in the parents of the proband indicated that the disorder may have resulted from homozygous recessive inheritance of the mutant allele from an ancestor shared by both parents. The mutant C/EBPepsilon(32) protein localized in the cytoplasm rather than the nucleus and was unable to activate transcription. Consistent with this, a significant decrease in the levels of the messenger RNAs (mRNAs) encoding the secondary granule protein human 18-kd cationic antimicrobial protein (hCAP-18)/LL-37 and the primary granule protein bactericidal/permeability-increasing protein were observed in the patient. The hCAP-18 mRNA was induced by overexpression of C/EBPepsilon(32) in the human myeloid leukemia cell line, U937, supporting the hypothesis that C/EBPepsilon is a key regulator of granule gene synthesis. This study strongly implicates mutation of the C/EBPepsilon gene as the primary genetic defect involved in the development of neutrophil SGD and defines its mechanism of inheritance.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
5/39. Successful unrelated BMT in a patient with Kostmann syndrome complicated by pre-transplant pulmonary 'bacterial' abscesses.Kostmann syndrome, severe congenital neutropenia, is often associated with life-threatening bacterial infections. A 5-year-old girl with Kostmann syndrome developed pulmonary abscesses. She was refractory to granulocyte colony-stimulating factor and antibiotics. She underwent unrelated HLA-matched BMT. Myeloablative conditioning consisted of 12-Gy TBI with lung shielding, antithymocyte globulin, etoposide, and cyclophosphamide. After successful engraftment, the pulmonary abscesses resolved by day 75 post-transplant. Although the option of transplantation is not established in the setting of unrelated HLA-matched BMT in Kostmann syndrome, this case may provide useful information. Furthermore, pre-transplant pulmonary bacterial abscesses may not be a contraindication for BMT in some patients with Kostmann syndrome.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
6/39. Acute rheumatic fever in a patient with glycogen storage disease type Ib: causal or coincidental simultaneous occurrence?We report a Caucasian female who was diagnosed with glycogen storage disease type Ib (GSD-Ib) at the age of 4 months and whose clinical course was complicated by neutropenia and very frequent episodes of infection, including tonsillopharyngitis. Recurrent group A streptococcal infections resulted in multiple episodes of extremely high serum levels of antibodies to streptolysin O (5,000 IU/ml) and DNAse B (6,000 IU/ ml). At the age of 14 years she presented with carditis, migratory arthritis, fever, elevated erythrocyte sedimentation rate as well as serological evidence for recent streptococcal infection providing a diagnosis of acute rheumatic fever. CONCLUSION: the occurrence of these two very rare disorders in our patient may indicate that this association is not coincidental because neutrophil dysfunction in glycogen storage disease type Ib may have predisposed this patient to acute rheumatic fever due to increased susceptibility to group A streptococcal infections. aberrant glycogenolysis and gluconeogenesis, neutropenia and neutrophil dysfunction are regular findings in GSD-Ib. neutropenia and neutrophil dysfunction in patients with GSD-Ib are due to defects in myeloid maturation, impaired neutrophil motility, defective chemotaxis and phagocytosis and diminished bactericidal activity resulting in recurrent bacterial infections.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
7/39. Recurrent bacterial infections in four siblings with neutropenia, eosinophilia, hyperimmunoglobulinemia A, and defective neutrophil chemotaxis.Four siblings with recurrent bacterial infections, neutrophil chemotactic defect, neutropenia, and eosinophilia were studied. During periods of infection the peripheral neutrophil count increased to normal, while the eosinophilia disappeared. In addition, these children had high levels of serum IgA and poor antibody responses to tetanus and polio vaccinations. A defect in cell-mediated immunity was demonstrated by an absent or weak reactivity to various skin test antigens and by abnormal lymph node histology. Thus these siblings had an unusual combination of defective inflammatory response and immunologic abnormalities.- - - - - - - - - - ranking = 5keywords = bacterial infection (Clic here for more details about this article) |
8/39. Long-term follow-up of granulocyte colony-stimulating factor receptor mutations in patients with severe congenital neutropenia: implications for leukaemogenesis and therapy.Severe congenital neutropenia (SCN) is characterized by profound neutropenia, recurrent severe bacterial infections and maturation arrest in the myeloid lineage. granulocyte colony-stimulating factor (G-CSF) treatment results in clinical improvement in over 90% of cases. Point mutations of the G-CSF receptor (G-CSFR) have been implicated in the progression of SCN to acute myeloid leukaemia (AML). Data are presented here on the 9-year follow-up of seven patients and the further screening of 18 other cases. One of the two original cases with a G-CSFR mutation has improved clinically; nevertheless, mutant dna could still be detected at a very low level > 8 years after identification. The second child with a mutation progressed to myelodysplasia/AML 5 years after her mutation was detected. No mutations were found in the 18 new cases. One of three transformed cases had a G-CSFR mutation. This work is in agreement with the suggestion that G-CSFR mutations may provide a survival advantage to haemopoietic stem cells, but argues against the inevitability of leukaemic progression in their presence. Furthermore, the low frequency of G-CSFR mutations in SCN and the importance of regular screening and close clinical and laboratory follow-up if a mutation is found were demonstrated.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
9/39. A new disorder of lymphocyte apoptosis: combination of autoimmunity, infectious lymphadenopathy, double negative T cells, and impaired activation-induced cell death.A new symptom-complex is described characterized by manifestations of autoimmune disease, infectious lymphadenopathy, double negative T cells, and impaired activation-induced cell death that developed in late adolescence. Similarities, but also significant differences, to autoimmune lymphoproliferative syndromes (ALPS, Canale-Smith syndrome) and autoimmune lymphoproliferative disease (ALD, Dianzani syndrome), were observed. The main clinical features were recurrent bacterial infections with subsequent lymphadenopathy due to autoimmune neutropenia. Laboratory results revealed a large proportion of alphabetaTCR positive, CD4 negative, CD8 negative, peripheral T cells, and a decreased apoptosis upon activation with phytohemagglutinin and interleukin 2, but normal Fas-mediated apoptosis. Genetic investigations excluded mutations in Fas gene death domain and in the 4 exons of Fas ligand gene. Despite unknown pathogenesis, this new syndrome might belong to the growing group of diseases with defects in apoptosis.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
10/39. Uneventful outcome of unrelated hematopoietic stem cell transplantation in a patient with leukemic transformation of Kostmann syndrome and long-lasting invasive pulmonary mycosis.Kostmann syndrome (KS) is an inherited hematological disorder characterized by an absolute neutrophil count (ANC) <0.2 x 109/L and life-threatening bacterial infections. Granulocyte-colony stimulating factor (G-CSF) makes it possible to reach an ANC of 1.0 x 109/L and consequently to reduce significantly the occurrence of severe infections. Absence of response to G-CSF, G-CSF receptor mutation, and leukemic transformation are absolute indications to perform hematopoietic stem cell transplantation (HSCT). Pulmonary mycosis does not represent an absolute contraindication to bone marrow transplantation (BMT), although a relapse rate of 30-50% has been reported, despite adequate medical and surgical treatment. Mycotic pneumonia recurrence shows a mortality rate above 80%, especially in the presence of persisting immunosuppression. We report on a KS patient with long-lasting fungal pneumonia who developed myelodysplasia and subsequent acute myeliod leukemia (AML) conversion resistant to antiblastic therapy. Despite surgical excision and secondary prophylaxis, recurrence of the pulmonary lesion occurred prior to the unrelated HSCT. In spite of these poor prognostic characteristics, outcome was uneventful and the patient is alive and well in continuous complete remission with no signs of fungal infection.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
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