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1.
S Afr Med J ; 110(3): 197-203, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32657696

RESUMO

BACKGROUND: The primary immunodeficiency diseases (PIDs) constitute a diverse and ever-expanding group of inborn errors affecting a wide range of immune functions. They are not well documented in sub-Saharan Africa. OBJECTIVES: To describe the spectrum of PIDs at a tertiary paediatric hospital. METHODS: A retrospective descriptive study of PIDs diagnosed at Red Cross War Memorial Children's Hospital, Cape Town, South Africa (SA), between 1975 and 2017 was undertaken. RESULTS: We identified 252 children with PIDs, spanning eight of the nine categories listed in the 2017 classification of the International Union of Immunological Societies. Predominantly antibody deficiencies, combined immunodeficiencies with associated syndromic features, and immunodeficiencies affecting cellular and humoral immunity accounted for most children with PIDs (n=199, 79.0%). The mean age (standard deviation) at diagnosis was 46 (50) months, and the male/female ratio was 1.5:1. There was a history of parental consanguinity in 3 cases (1.2%). Recurrent infection was the most prevalent presenting phenotype, manifesting in 177 patients (70.2%). Genetic or chromosomal confirmation was obtained in 42/252 cases (16.7%). Common interventions used to prevent infection were antimicrobial prophylaxis and immunoglobulin replacement therapy, administered to 95 (37.7%) and 93 (36.9%) of the patients, respectively. Six of 7 children who underwent haematopoietic stem cell transplantation (HSCT) had successful outcomes. The 7th patient died 2 months after HSCT from overwhelming infection. Although we could not account for the children lost to follow-up during the study period, 53 deaths were confirmed (21.0%). CONCLUSIONS: Several challenges exist in the recognition and treatment of children with PIDs in our setting. These include limited access to genetic diagnostics and HSCT. Suboptimal treatment options contribute to the overall mortality of PIDs in SA.


Assuntos
Doenças da Imunodeficiência Primária/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Masculino , Doenças da Imunodeficiência Primária/epidemiologia , Doenças da Imunodeficiência Primária/genética , Doenças da Imunodeficiência Primária/mortalidade , Cruz Vermelha , Estudos Retrospectivos , África do Sul/epidemiologia , Fatores de Tempo
2.
Int J Infect Dis ; 97: 117-125, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32497805

RESUMO

BACKGROUND: Disseminated Bacillus Calmette-Guérin (BCG) disease (BCGosis) is a classical feature of children with primary immunodeficiency disorders (PIDs). METHODS: A 15-year retrospective review was conducted in KK Women's and Children's Hospital in Singapore, from January 2003 to October 2017. RESULTS: Ten patients were identified, the majority male (60.0%). The median age at presentation of symptoms of BCG infections was 3.8 (0.8 - 7.4) months. All the patients had likely underlying PIDS - four with Severe Combined Immunodeficiency (SCID), three with Mendelian Susceptibility to Mycobacterial Diseases (MSMD), one with Anhidrotic Ectodermal Dysplasia with Primary Immunodeficiency (EDA-ID), one with combined immunodeficiency (CID), and one with STAT-1 gain-of-function mutation. Definitive BCGosis was confirmed in all patients by the identification of Mycobacterium bovis subsp BCG from microbiological cultures. The susceptibility profiles of Mycobacterium bovis subsp BCG are as follows: Rifampicin (88.9%), Isoniazid (44.47%), Ethambutol (100.0%), Streptomycin (100.0%), Kanamycin (100.0%), Ethionamide (25.0%), and Ofloxacin (100.0%). Four patients (40.0%) received a three-drug regimen. Five patients (50.0%) underwent hematopoietic stem cell transplant (HSCT), of which three (60%) have recovered. Overall mortality was 50.0%. CONCLUSION: Disseminated BCG disease (BCGosis) should prompt immunology evaluation to determine the diagnosis of the immune defect. A three-drug regimen is adequate for treatment if the patient undergoes early HSCT.


Assuntos
Vacina BCG/efeitos adversos , Mycobacterium bovis , Doenças da Imunodeficiência Primária/complicações , Tuberculose/etiologia , Vacina BCG/uso terapêutico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Doenças da Imunodeficiência Primária/terapia , Estudos Retrospectivos , Singapura , Tuberculose/tratamento farmacológico , Tuberculose/etnologia
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(3): 1025-1031, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32552976

RESUMO

OBJECTIVE: To investigate the prevalence of respiratory viral infections in patients with primary immunodeficiency disease (PID) during hematopoietic stem cell transplantation. METHODS: 108 specimens of nasopharyngeal aspirate were collected from 22 PID patients before and after hematopoietic stem cell transplantation from July 2016 to July 2018 in the Department of Hematology. The TR-PCR was used to detect for respiratory viruses including respiratory syncytial virus(RSV),human metapneumoviros(hMPV),coronavirus(CoV) and parainfluenza 1-3 (PIV1-3). And the clinical characteristics and co-infection were analyzed. RESULTS: Among the total 108 specimens, viral pathogens were identified in 41 (37.96%) specimens. Among which the pathogens of highest detection rate was RSV (25.9%). Different types of PID showed different virus infection rates, among which the highest infection rate was severe combined immunodeficiency disease (SCID) patients, with the virus detection rate was 57.9%. The incidence of co-infection with two or more than two viruses was 19.5%. CONCLUSION: Patients with PID who undergo hematopoietic stem cell transplantation are more susceptible to respiratory viruses. RSV is an important respiratory tract virus pathogen after hematopoietic stem cell transplantation.


Assuntos
Metapneumovirus , Doenças da Imunodeficiência Primária , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Humanos , Doenças da Imunodeficiência Primária/terapia
4.
J Cardiothorac Surg ; 15(1): 141, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32539831

RESUMO

BACKGROUND: Good syndrome is a rare condition, manifesting as immunodeficiency due to hypogammaglobulinemia associated with thymoma. Herein, we present a patient with Good syndrome whose thymoma was resected after treatment of cytomegalovirus hepatitis. CASE PRESENTATION: The patient was a 45-year-old woman presenting with fever, cough, and nasal discharge, and was diagnosed with thymoma and hypogammaglobulinemia. She subsequently developed cytomegalovirus hepatitis that was treated by immunoglobulin. After resolution of the hepatitis, she underwent thymectomy through a left anterior thoracotomy. Her postoperative course was uneventful, and while receiving ongoing immunoglobulin therapy, she has been doing well without signs of infection. CONCLUSIONS: Management of infections is important for patients with Good syndrome. To minimize the risk of perioperative infection, we should take care while planning the surgical approach and procedure.


Assuntos
Agamaglobulinemia/complicações , Infecções por Citomegalovirus/complicações , Doenças da Imunodeficiência Primária/complicações , Timoma/complicações , Timoma/cirurgia , Neoplasias do Timo/complicações , Neoplasias do Timo/cirurgia , Agamaglobulinemia/terapia , Comorbidade , Citomegalovirus , Feminino , Hepatite/complicações , Hepatite/cirurgia , Humanos , Pessoa de Meia-Idade , Doenças da Imunodeficiência Primária/terapia , Timectomia
5.
PLoS One ; 15(5): e0233016, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32413055

RESUMO

Tunneled central venous catheters (TCVCs) provide prolonged intravenous access for pediatric patients with severe primary immunodeficiency disease (PID) undergoing hematopoietic stem cell transplantation (HSCT). However, little is known about the epidemiology and clinical significance of TCVC-related morbidity in this particular patient group. We conducted the retrospective analysis of patients with severe PID who received percutaneous landmark-guided TCVC implantation prior to HSCT. We analyzed 92 consecutive TCVC implantations in 69 patients (median [interquartile range] age 3.0 [0-11] years) with severe combined immune deficiency (n = 39, 42.4%), chronic granulomatous disease (n = 17, 18.4%), and other rare PID syndromes (n = 36, 39.2%). The median length of TCVC observation was 144.1 (85.5-194.6) days with a total of 14,040 catheter days at risk (cdr). The overall rate of adverse events during catheter insertion was 17.4% (n = 16) and 25.0% during catheter dwell period (n = 23, catheter risk [CR] per 1000 cdr = 1.64). The most common complication was TCVC-related infection with an overall prevalence of 9.8% (n = 9, CR = 0.64), followed by late dislocation (n = 6, 6.5%, CR = 0.43), early dislocation (n = 4, 4.3%) and catheter dysfunction (n = 4, 4.3%, CR = 0.28). TCVCs are safe in children with severe PID undergoing HSCT with relatively low rates of TCVC-related infection.


Assuntos
Cateteres Venosos Centrais/efeitos adversos , Transplante de Células-Tronco Hematopoéticas , Doenças da Imunodeficiência Primária/terapia , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/etiologia , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/métodos , Criança , Pré-Escolar , Feminino , Alemanha/epidemiologia , Doença Granulomatosa Crônica/terapia , Humanos , Lactente , Recém-Nascido , Masculino , Morbidade , Estudos Retrospectivos , Fatores de Risco , Segurança , Imunodeficiência Combinada Severa/terapia
6.
PLoS One ; 15(5): e0233342, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32470021

RESUMO

Increasing physicians' awareness is one of the main ways to improve early diagnosis of rare diseases. A survey among physicians of different specialties to evaluate the knowledge about primary immunodeficiencies (PID) was conducted in 2016 and in 2019 -before and after the implementation of an educational program. We compare responses from 82 doctors who participated in the 2016 survey, and 67 doctors who have taken part in the survey in 2019: pediatricians, general practitioners / family physicians and physicians of pediatric sub specialties. The percentage of correct answers to all survey questions after the implementation of the educational program has significantly increased (79.0% in 2019 versus 58.3% in 2016, P<0.0001). This increase in the percentage of correct answers was noted among the surveyed doctors of all specialties. Particular progress was found among pediatricians, who have achieved more than 80% of correct answers. In 2019 the doctors demonstrated better knowledge on the warning signs of PID and specific features of Nijmegen breakage syndrome, DiGeorge syndrome and ataxia-telangiectasia syndrome. Thus, the implementation of an educational program improved physicians' awareness of PIDs, and will contribute to early detection of PIDs and their medical care.


Assuntos
Competência Clínica/estatística & dados numéricos , Clínicos Gerais/normas , Doenças da Imunodeficiência Primária/psicologia , Qualidade da Assistência à Saúde/normas , Adulto , Idoso , Competência Clínica/normas , Feminino , Clínicos Gerais/psicologia , Clínicos Gerais/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doenças da Imunodeficiência Primária/terapia , Inquéritos e Questionários
7.
Clin Immunol ; 214: 108376, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32135276

RESUMO

Primary immunodeficiencies (PIDs) are a heterogeneous group of monogenic inborn errors of immunity. The genetic causes of these diseases can be identified using whole exome sequencing (WES). Here, DNA samples from 106 patients with a clinical suspicion of PID were subjected to WES in order to test the diagnostic yield of this test in a highly consanguineous community. A likely genetic diagnosis was achieved in 70% of patients. Several factors were considered to possibly influence the diagnostic rate of WES among our cohort including early age, presence of consanguinity, family history suggestive of PID, the number of family members who underwent WES and the clinical phenotype of the patient. The highest diagnostic rate was in patients with combined immunodeficiency or with a syndrome. Notably, WES findings altered the clinical management in 39% (41/106) of patients in our cohort. Our findings support the use of WES as an important diagnostic tool in patients with suspected PID, especially in highly consanguineous communities.


Assuntos
Mutação , Doenças da Imunodeficiência Primária/diagnóstico , Sequenciamento Completo do Exoma , Adolescente , Adulto , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/genética , Criança , Pré-Escolar , Tomada de Decisão Clínica , Consanguinidade , Gerenciamento Clínico , Feminino , Genótipo , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Recém-Nascido , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/genética , Israel/epidemiologia , Masculino , Doenças da Imunodeficiência Primária/epidemiologia , Doenças da Imunodeficiência Primária/genética , Doenças da Imunodeficiência Primária/terapia , Adulto Jovem
8.
Clin Immunol ; 212: 108248, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31382036
9.
J Allergy Clin Immunol ; 145(1): 46-69, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31568798

RESUMO

Genetic testing has become an integral component of the diagnostic evaluation of patients with suspected primary immunodeficiency diseases. Results of genetic testing can have a profound effect on clinical management decisions. Therefore clinical providers must demonstrate proficiency in interpreting genetic data. Because of the need for increased knowledge regarding this practice, the American Academy of Allergy, Asthma & Immunology Primary Immunodeficiency Diseases Committee established a work group that reviewed and summarized information concerning appropriate methods, tools, and resources for evaluating variants identified by genetic testing. Strengths and limitations of tests frequently ordered by clinicians were examined. Summary statements and tables were then developed to guide the interpretation process. Finally, the need for research and collaboration was emphasized. Greater understanding of these important concepts will improve the diagnosis and management of patients with suspected primary immunodeficiency diseases.


Assuntos
Testes Genéticos , Doenças da Imunodeficiência Primária , Asma , Humanos , Doenças da Imunodeficiência Primária/diagnóstico , Doenças da Imunodeficiência Primária/genética , Doenças da Imunodeficiência Primária/terapia , Estados Unidos
10.
J Pediatr Hematol Oncol ; 42(2): 156-159, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31033788

RESUMO

Gain of function mutations in the p110δ catalytic subunit of the phosphatidylinositol-3-OH kinase (PIK3CD) classified as activated phosphoinositide 3-kinase delta syndrome (APDS) are the cause of a primary immunodeficiency characterized by recurrent sinopulmonary infections, and lymphoproliferation. Previously, autoimmunity and Epstein-Barr virus-related B-cell lymphoma have been documented for patients with APDS; here, we present a case that extends the picture, as the patient shows the full diagnostic criteria of hemophagocytic lymphohistiocytosis at 6 months of age. He experienced Hodgkin lymphoma as a 2.5-year-old baby. Next-generation sequencing returned a de novo heterozygous missense variant in PIK3CD (LRG_191t1: c.3061G>A; p.Glu1021Lys), confirming the primary immunodeficiency. After 2 courses of ifosfamide, cisplatin, and etoposide combined with brentuximab, the patient successfully underwent allogeneic hematopoietic stem cell transplantation from his HLA full matched sister, and he has been well for 18 months after that. The hematologist treating Hodgkin lymphoma and/or hemophagocytic lymphohistiocytosis should be vigilant about the possible underlying immune deficiency, and they should consider APDS in their differential diagnosis.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases/genética , Doença de Hodgkin/patologia , Linfo-Histiocitose Hemofagocítica/patologia , Mutação , Doenças da Imunodeficiência Primária/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/complicações , Doença de Hodgkin/genética , Doença de Hodgkin/terapia , Humanos , Lactente , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/genética , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Doenças da Imunodeficiência Primária/complicações , Doenças da Imunodeficiência Primária/genética , Doenças da Imunodeficiência Primária/terapia , Prognóstico
11.
Pediatr Ann ; 48(12): e489-e494, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31830289

RESUMO

This article presents the general pediatrician with a broad overview of the rapidly expanding spectrum of primary immune deficiencies, which are diseases that go beyond the classic description of increased susceptibility to infections and also those with predisposition to autoimmunity, malignancy, and immune dysregulation. Readers are guided through the three proposed categories under the umbrella term of primary immune deficiencies. These categories are lack of function, inappropriate surveillance and clearance, and inadequate control immune dysregulation. This article presents an illustrative distribution of the interrelated groups of immune disorders. [Pediatr Ann. 2019;48(12):e489-e494.].


Assuntos
Autoimunidade/imunologia , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/epidemiologia , Neoplasias/epidemiologia , Doenças da Imunodeficiência Primária/diagnóstico , Doenças da Imunodeficiência Primária/terapia , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Gerenciamento Clínico , Feminino , Humanos , Síndromes de Imunodeficiência/terapia , Masculino , Neoplasias/etiologia , Prevalência , Doenças da Imunodeficiência Primária/epidemiologia , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Resultado do Tratamento , Estados Unidos
12.
Hematology Am Soc Hematol Educ Program ; 2019(1): 443-448, 2019 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-31808899

RESUMO

Recent advances in genomics have greatly expanded the spectrum of primary immune deficiencies (PIDs). Along with the identification of pathogenic variants in novel genes, distinct phenotypes have been associated with different variants in the same gene. Although PIDs have been historically defined based on increased susceptibility to infections, immune dysregulation has emerged as a frequent and in some cases, predominant phenotype. Autoimmune cytopenias with onset in childhood, lasting longer than 12 months, and affecting multiple lineages should raise the suspicion of a possible PID with monogenic origin. Characterization of the various molecular and cellular mechanisms responsible for these unusual manifestations of PIDs, although at times resource intensive, may allow for targeted intervention in many of them.


Assuntos
Doenças da Imunodeficiência Primária/genética , Doenças da Imunodeficiência Primária/metabolismo , Doenças da Imunodeficiência Primária/terapia , Criança , Humanos , Masculino
14.
JCI Insight ; 4(24)2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31687976

RESUMO

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome immunodeficiency is caused by autosomal dominant gain-of-function mutations in chemokine receptor CXCR4. Patient WHIM-09 was spontaneously cured by chromothriptic deletion of 1 copy of 164 genes, including the CXCR4WHIM allele, presumably in a single hematopoietic stem cell (HSC) that repopulated HSCs and the myeloid lineage. Testing the specific contribution of CXCR4 hemizygosity to her cure, we previously demonstrated enhanced engraftment of Cxcr4+/o HSCs after transplantation in WHIM (Cxcr4+/w) model mice, but the potency was not quantitated. We now report graded-dose competitive transplantation experiments using lethally irradiated Cxcr4+/+ recipients in which mixed BM cells containing approximately 5 Cxcr4+/o HSCs and a 100-fold excess of Cxcr4+/w HSCs achieved durable 50% Cxcr4+/o myeloid and B cell chimerism in blood and approximately 20% Cxcr4+/o HSC chimerism in BM. In Cxcr4+/o/Cxcr4+/w parabiotic mice, we observed 80%-100% Cxcr4+/o myeloid and lymphoid chimerism in the blood and 15% Cxcr4+/o HSC chimerism in BM from the Cxcr4+/w parabiont, which was durable after separation from the Cxcr4+/o parabiont. Thus, CXCR4 haploinsufficiency likely significantly contributed to the selective repopulation of HSCs and the myeloid lineage from a single chromothriptic HSC in WHIM-09. Moreover, the results suggest that WHIM allele silencing of patient HSCs is a viable gene therapy strategy.


Assuntos
Haploinsuficiência , Transplante de Células-Tronco Hematopoéticas , Leucopenia/terapia , Doenças da Imunodeficiência Primária/terapia , Receptores CXCR4/genética , Verrugas/terapia , Animais , Cromotripsia , Modelos Animais de Doenças , Feminino , Mutação com Ganho de Função , Terapia Genética/métodos , Humanos , Leucopenia/genética , Masculino , Camundongos , Doenças da Imunodeficiência Primária/complicações , Doenças da Imunodeficiência Primária/genética , Quimeras de Transplante , Verrugas/complicações , Verrugas/genética
15.
BMC Pediatr ; 19(1): 410, 2019 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684895

RESUMO

BACKGROUND: Primary immunodeficiency disease (PID) is a disorder caused by an inherited flaw in the immune system that increases the susceptibility to infections. METHODS: In this study, 112 children with PID were diagnosed and classified based on the 2017 criteria presented by the International Union of Immunological Societies (IUIC) in a single tertiary care center from January 2013 to November 2018. We retrospectively studied the clinical features of those PID children and followed-up them as well. RESULTS: It was revealed that male/female ratio was 6:1. The most frequent diagnosed PID was severe combined immunodeficiency (SCID) (28.6%) and hyper-IgM (HIGM) syndrome (24.1%), followed by predominantly antibody deficiencies (17.8%). Combined immunodeficiencies with associated or syndromic features (12.5%) and congenital defects of phagocyte number, function, or both (10.7%) were less common in our center compared with SCID and HIGM syndrome. Besides, we found that 20 children (17.8%) had a positive family history of PID, and almost all cases (97.3%) had a history of recurrent infection. Recurrent respiratory tract infection was among the most common symptoms, followed by the bacterial infection of the skin and mucous membranes and diarrhea. Additionally, adverse event following immunization (AEFI) was found in 20.5% of the patients, and immune disorder was commonly observed in PID patients. In the present study, 47 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 2-year overall survival (OS) rate for these patients was 78.7% (37/47). It is noteworthy that OS widely differed among PID patients with different phenotypes who underwent allo-HSCT. The 2-year OS rate for SCID, HIGM syndrome, and the remaining of PID patients who underwent allo-HSCT was 14.3, 83.3, and 100%, respectively. CONCLUSIONS: PID typically emerges at early age. Recurrent infection and serious infection were the most common clinical manifestations. Allo-HSCT is a relatively effective therapeutic strategy for PID patients.


Assuntos
Doenças da Imunodeficiência Primária/epidemiologia , Criança , Pré-Escolar , China , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Síndrome de Imunodeficiência com Hiper-IgM/diagnóstico , Síndrome de Imunodeficiência com Hiper-IgM/epidemiologia , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/epidemiologia , Lactente , Infecções/epidemiologia , Masculino , Doenças da Imunodeficiência Primária/diagnóstico , Doenças da Imunodeficiência Primária/terapia , Recidiva , Infecções Respiratórias/epidemiologia , Estudos Retrospectivos , Imunodeficiência Combinada Severa/epidemiologia , Dermatopatias Bacterianas/epidemiologia , Centros de Atenção Terciária
16.
Transfusion ; 59(12): 3570-3574, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31710384

RESUMO

BACKGROUND: Delayed hemolytic reactions are potential complications of incompatible transfusions and are usually associated with the identification of a new antibody on serologic studies, following a second immunization event. However, in rare cases, the antibody investigation remains negative even if the clinical presentation would lead one to suspect otherwise. CASE REPORT: A 44-year-old woman with hereditary hemorrhagic telangiectasia presented to the emergency department with hematuria and low back pain after she had received three units of RBCs 2 weeks earlier. Hematology and biochemistry results were consistent with delayed hemolytic transfusion reaction, but surprisingly, serologic antibody investigations were negative. It was only when her plasma was tested with enzyme (ficin)-treated panel cells that anti-e was finally detected, with a 3+ reaction with all homozygous e+ cells. No reaction was seen with heterozygous e+ cells. Four months later, an anti-K was also detected on standard panels, while the anti-e remained detectable only with ficin-treated panel cells. Three years later, both antibodies had vanished and remained undetectable. The weakness of anti-e reaction, combined with the quick evanescence of both antibodies led to the suspicion of a potential underlying immunodeficiency disorder, which was confirmed by low immunoglobulin levels on two occasions. CONCLUSION: To our knowledge, this is the first case of immunodeficiency disorder diagnosed after the identification of evanescent antibody reactions. This case also outlines the importance of a good clinical history that should lead to further investigations when a hemolytic transfusion reaction is suspected.


Assuntos
Hemólise/fisiologia , Telangiectasia Hemorrágica Hereditária/terapia , Reação Transfusional , Adulto , Anticorpos/metabolismo , Feminino , Ficina , Humanos , Imunoglobulinas/metabolismo , Doenças da Imunodeficiência Primária/terapia
17.
Curr Allergy Asthma Rep ; 19(11): 52, 2019 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-31741098

RESUMO

PURPOSE OF REVIEW: Hematopoietic cell transplantation (HCT) is an established curative treatment for children with primary immunodeficiencies. This article reviews the latest developments in conditioning regimens for primary immunodeficiency (PID). It focuses on data regarding transplant outcomes according to newer reduced toxicity conditioning regimens used in HCT for PID. RECENT FINDINGS: Conventional myeloablative conditioning regimens are associated with significant acute toxicities, transplant-related mortality, and late effects such as infertility. Reduced toxicity conditioning regimens have had significant positive impacts on HCT outcome, and there are now well-established strategies in children with PID. Treosulfan has emerged as a promising preparative agent. Use of a peripheral stem cell source has been shown to be associated with better donor chimerism in patients receiving reduced toxicity conditioning. Minimal conditioning regimens using monoclonal antibodies are in clinical trials with promising results thus far. Reduced toxicity conditioning has emerged as standard of care for PID and has resulted in improved transplant survival for patients with significant comorbidities.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Doenças da Imunodeficiência Primária/terapia , Condicionamento Pré-Transplante/métodos , Bussulfano/análogos & derivados , Bussulfano/farmacocinética , Bussulfano/uso terapêutico , Humanos , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Doenças da Imunodeficiência Primária/metabolismo , Vidarabina/análogos & derivados , Vidarabina/farmacocinética , Vidarabina/uso terapêutico
19.
Emerg Infect Dis ; 25(11): 2005-2012, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31625840

RESUMO

Patients with immunodeficiency-associated vaccine-derived poliovirus (iVDPV) are potential poliovirus reservoirs in the posteradication era that might reintroduce polioviruses into the community. We update the iVDPV registry in Iran by reporting 9 new patients. In addition to national acute flaccid paralysis surveillance, cases were identified by screening nonparalyzed primary immunodeficiency (PID) patients. Overall, 23 iVDPV patients have been identified since 1995. Seven patients (30%) never had paralysis. Poliovirus screening accelerated the iVDPV detection rate in Iran after 2014.The iVDPV infection rate among nonparalyzed patients with adaptive PID was 3.1% (7/224), several folds higher than previous estimates. Severe combined immunodeficiency patients had the highest risk for asymptomatic infection (28.6%) compared with other PIDs. iVDPV2 emergence has decreased after the switch from trivalent to bivalent oral poliovirus vaccine in 2016. However, emergence of iVDPV1 and iVDPV3 continued. Poliovirus screening in PID patients is an essential step in the endgame of polio eradication.


Assuntos
Poliomielite/epidemiologia , Poliomielite/etiologia , Vacinas contra Poliovirus/efeitos adversos , Poliovirus/imunologia , Doenças da Imunodeficiência Primária/complicações , Doenças da Imunodeficiência Primária/epidemiologia , Adolescente , Adulto , Doenças Assintomáticas , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Irã (Geográfico)/epidemiologia , Masculino , Programas de Rastreamento , Avaliação de Resultados em Cuidados de Saúde , Poliomielite/prevenção & controle , Poliomielite/virologia , Vacinas contra Poliovirus/imunologia , Doenças da Imunodeficiência Primária/terapia , Vigilância em Saúde Pública , Sistema de Registros , Avaliação de Sintomas , Vacinação , Adulto Jovem
20.
PLoS One ; 14(10): e0223861, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31613907

RESUMO

Patients with primary or secondary antibody deficiency (PAD or SAD) are at increased risk of recurrent infections that can be alleviated by immunoglobulin replacement therapy (IRT). In addition to replenishing antibody levels, IRT has been suggested to modulate immune response in patients with antibody deficiency. Although both commonly treated with IRT, the underlying causes of PAD and SAD vary greatly, suggesting differential modulation of T-cell function that may lead to different responses to IRT. To explore this, peripheral blood mononuclear cells (PBMCs) were sampled from 17 PAD and 14 SAD patients before and 2-10 months after initiation of IRT, and analyzed for changes in T-cell phenotype and function. Proportions of CD4, CD8, Treg, or memory T-cells did not significantly change post-IRT compared to pre-IRT. However, we report distinct modulation in T-cell function between PAD and SAD patients post-IRT. Upon α-CD3/CD28 stimulation, proportion of IFN-γ+ CD4 and CD8 T-cells increased in SAD (p = 0.005) but not PAD patients post-IRT compared to baseline. Interestingly, total T-cell proliferation was reduced post-IRT in both PAD and SAD patients, although the reduction in proliferation was primarily due to reduced CD4 T-cell proliferation in PAD (p = 0.025) in contrast to CD8 T-cells in SAD (p = 0.042). In summary, even though IRT provides patients with passive humoral immunity-mediated protection in PAD and SAD, our findings suggest that IRT immunomodulation of T-cells is different in T-cell subsets depending on underlying immunodeficiency.


Assuntos
Agamaglobulinemia/terapia , Imunização Passiva/métodos , Doenças da Imunodeficiência Primária/terapia , Linfócitos T/metabolismo , Administração Intravenosa , Agamaglobulinemia/imunologia , Idoso , Proliferação de Células , Citocinas/metabolismo , Feminino , Humanos , Injeções Subcutâneas , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Doenças da Imunodeficiência Primária/imunologia , Linfócitos T/citologia , Resultado do Tratamento
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