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1.
Iran J Allergy Asthma Immunol ; 18(4): 447-451, 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31522453

RESUMO

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defective phagocytic NADPH oxidase, causing a complete lack or significant decrease in the production of microbicidal reactive oxygen metabolites. It mainly affects male children; however, there are scarce reports of adult females diagnosed with X-linked-CGD attributed to an extremely skewed X-chromosome inactivation. This condition is characterized by severe and recurrent infections that usually develop after childhood. In clinical practice, physicians who usually confront these patients should suspect this entity and differentiate it from a secondary immunodeficiency. Here, we report a 38-year-old Mexican female with juvenile-onset X linked-CGD, caused by a de novo mutation and extremely skewed X-inactivation, whose clinical features were similar to those in patients with classic X-linked-CDG.

2.
J Allergy Clin Immunol ; 144(4): 897-905, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31419546

RESUMO

Severe combined immunodeficiency (SCID) represents the most lethal form of primary immunodeficiency, with mortality rates of greater than 90% within the first year of life without treatment. Hematopoietic stem cell transplantation and gene therapy are the only curative treatments available, and the best-known prognostic factors for success are age at diagnosis, age at hematopoietic stem cell transplantation, and the comorbidities that develop in between. There are no evidence-based guidelines for standardized clinical care for patients with SCID during the time between diagnosis and definitive treatment, and we aim to generate a consensus management strategy on the supportive care of patients with SCID. First, we gathered available information about SCID diagnostic and therapeutic guidelines, then we developed a document including diagnostic and therapeutic interventions, and finally we submitted the interventions for expert consensus through a modified Delphi technique. Interventions are grouped in 10 topic domains, including 123 "agreed" and 38 "nonagreed" statements. This document intends to standardize supportive clinical care of patients with SCID from diagnosis to definitive treatment, reduce disease burden, and ultimately improve prognosis, particularly in countries where newborn screening for SCID is not universally available and delayed diagnosis is the rule. Our work intends to provide a tool not only for immunologists but also for primary care physicians and other specialists involved in the care of patients with SCID.

3.
Rheumatol Int ; 39(10): 1829-1838, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31312887

RESUMO

Kawasaki disease (KD) has features that appear supporting an infectious cause with a secondary deranged inflammatory/autoimmune response. The association of KD in adults with human immunodeficiency virus infection and the presence of KD in patients with immunodeficiency disorders support the infectious theory. We present four KD patients associated with immunodeficiencies: one with X-linked agammaglobulinemia, one with HIV infection, and two with leukemia; one of these patients also had Down syndrome. We did a literature search to find out all reported cases of immunodeficiency with KD in children. In immunodeficiency disorders, the inability of the immune system to eradicate the pathogens coupled to an exaggerated inflammatory response, especially in chronic granulomatous disease, may lead to the development of KD. The study of patients with immunodeficiencies complicated with KD may shed light into the etiopathogenesis of the disease.

6.
Clin Rheumatol ; 2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30343342

RESUMO

Previous studies have suggested an association of IgG levels (before and after IVIG infusion) with clinical outcomes in Kawasaki disease. A retrospective analysis was performed that included 418 patients with KD admitted to Tokyo Women's Medical University Yachiyo Medical Center to evaluate pre- and post-IVIG IgG levels and its relation to outcomes. All patients received an initial IVIG infusion and aspirin; IgG levels were measured in 350 patients before IVIG (pre-IVIG IgG levels) and in 373 patients 48 h after starting IVIG infusion (post-IVIG IgG levels). Media and standard deviation of the pre- and post-IVIG IgG levels were reported and classified according to age. Also, IgG z-scores were calculated according to normal values of IgG by age. The number of cases and corresponding percentage of non-responders were reported by age and total patients. The association of pre-IVIG, post-IVIG IgG levels and post-IVIG IgG level/pre-IVIG IgG level ratio with no-response was evaluated by simple logistic regression model based on the IgG z-score, and regression coefficient, X2 value, p, and R2 of Nagelkerke were reported. Pre-IVIG and post-IVIG IgG levels presented an association with non-responders with statistical significance. This association was more evident between post-IVIG IgG levels and non-responders. Regarding coronary alterations, it was not possible to perform an adequate statistical analysis due the small number of patients. Pre- and post-IVIG infusion IgG levels could be an important biomarker in KD as well as in other inflammatory conditions. Higher IgG levels could be associated with a more effective immunomodulatory action and associated with better clinical outcomes.

7.
Arch Cardiol Mex ; 2018 Apr 09.
Artigo em Espanhol | MEDLINE | ID: mdl-29650328

RESUMO

OBJECTIVES: To describe the cardiac manifestations in the acute phase of patients with Kawasaki disease treated in a third level Children's hospital in Mexico City, Mexico. METHODS: A cross-sectional study was conducted in patients with a diagnosis of Kawasaki disease treated in this hospital from August 1995 to December 2016. Information included patient demographics, clinical features, treatment used, electrocardiographic findings, extra-coronary echocardiographic findings, and the development of coronary artery aneurysms in the acute phase of the disease. RESULTS: The study included 508 cases of Kawasaki disease, with a mean age at diagnosis of 37.64±35.56 months (range from 2 to 200 months). Almost two-thirds (65.4%) of the patients were male, with a male/female ratio of 1.88:1. Complete Kawasaki disease was diagnosed in 79.2% of cases. Almost all cases (92.4%) received intravenous immunoglobulin. Twenty-eight patients (5.5%) developed arrhythmias, ST changes developed in 29 patients (5.6%), and 5 patients presented with ischaemic changes. In the initial echocardiographic evaluation, 51 patients (9.9%) were diagnosed with myocarditis, 72 patients (14.0%) with pericarditis and 77 cases (15.0%) developed pericardial effusion. Coronary artery anomalies were detected in 169 cases (32.9%). 32 cases were diagnosed as giant coronary aneurysms. Four patients died from cardiac complications in the acute phase of the disease. CONCLUSIONS: There has been an increase in the diagnosis of Kawasaki disease in Mexico. They presented with more cardiac complications than reported in literature. An increased knowledge of Kawasaki disease is required in Mexico in order to establish the cardiac outcomes of this group of patients.

8.
Expert Rev Clin Immunol ; 14(1): 83-93, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29202590

RESUMO

BACKGROUND: X-linked agammaglobulinemia (XLA) is characterized by the absence of immunoglobulin and B cells. Patients suffer from recurrent bacterial infections from early childhood, and require lifelong immunoglobulin replacement therapy. Mutations in BTK (Bruton's Tyrosine Kinase) are associated with this phenotype. Some patients that present XLA do not show typical clinical symptoms, resulting in delayed diagnosis due to the lack of a severe phenotype. This study presents a report of five XLA patients from four different families and attempts to determine a relationship between delayed diagnosis and the occurrence of BTK mutations. METHODS: Samples from patients with antibody deficiency were analyzed to determine BTK expression, immunophenotyping and mutation analysis. Clinical and laboratory data was analyzed and presented for each patient. RESULTS: Most patients presented here showed atypical clinical and laboratory data for XLA, including normal IgM, IgG, or IgA levels. Most patients expressed detectable BTK protein. Sequencing of BTK showed that these patients harbored missense mutations in the pleckstrin homology and Src-homology-2 domains. When it was compared to public databases, BTK sequencing exhibited a new change, along with three other previously reported changes. CONCLUSIONS: Delayed diagnosis and atypical manifestations in XLA might be related to mutation type and BTK expression.


Assuntos
Agamaglobulinemia/diagnóstico , Linfócitos B/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Infecção/diagnóstico , Mutação de Sentido Incorreto/genética , Domínios de Homologia à Plecstrina/genética , Proteínas Tirosina Quinases/genética , Domínios de Homologia de src/genética , Adolescente , Adulto , Tirosina Quinase da Agamaglobulinemia , Criança , Pré-Escolar , Análise Mutacional de DNA , Diagnóstico Tardio , Humanos , Imunoglobulinas/sangue , Imunoglobulinas/deficiência , Imunofenotipagem , Fenótipo , Adulto Jovem
9.
Rev Alerg Mex ; 64(1): 121-125, 2017 Jan-Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-28188718

RESUMO

BACKGROUND: Patients with common variable immunodeficiency show higher incidence of sinopulmonary and gastrointestinal infections, as well as lymphoproliferative and autoimmune diseases. The treatment of choice is replacement therapy with human gamma-globulin. Hematopoietic stem cell transplantation is a non-conventional therapeutic modality. CASE REPORT: Twenty-six-year old woman with no family or hereditary history of primary immune deficiencies or consanguinity, with repeated episodes of otitis, sinusitis, gastroenteritis and bronchitis since childhood. At adolescence, she was diagnosed with common variable immunodeficiency; she was prescribed intravenous gamma-globulin, broad-spectrum antimicrobials and macrolides. At 22 years of age, she underwent hematopoietic stem cell transplantation owing to continued severe infections. At 4 months, post-transplantation she was diagnosed with hypothyroidism and ovarian insufficiency. During the following 3 years, she had no infections, but at 25 years of age she had immune thrombocytopenic purpura diagnosed, which persists together with Raynaud's disease and upper respiratory tract persistent infections. At the moment of this report she is being treated with intravenous gamma-globulin and receiving prophylaxis with clarithromycin, without steroids or danazol. CONCLUSIONS: Given the high rate of morbidity and mortality associated and immune reconstitution failure, hematopoietic stem cell transplantation should be carefully evaluated in patients with treatment-unresponsive infections or lymphoproliferative disorders.

10.
Reumatol. clín. (Barc.) ; 12(5): 274-281, sept.-oct. 2016. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-155878

RESUMO

El lupus eritematoso sistémico (LES) es una enfermedad multisistémica poseedora de una gran variedad de presentaciones clínicas. Se han descrito enfermedades monogénicas que predisponen la aparición de LES. Como ejemplos tenemos a los defectos en los genes reguladores de la expresión de interferón alfa o a nivel del complemento, que presentan comportamientos clínicos particulares. Estos defectos presentan una presentación y severidad distintas, por lo que se puede argumentar que el lupus no es una sola enfermedad sino varias. El tratamiento se podría individualizar dependiendo del defecto subyacente que genere el subtipo de lupus (AU)


Systemic lupus erythematosus (SLE) is a multisystemic disease with a variety of clinical presentations. Monogenic predisposing conditions to the development of this disease have been described. As examples, an impaired expression of interferon-α regulated genes or complement deficiencies have been reported in patients with SLE, with particular clinical presentations. Those defects present particular presentations and a different severity, making an argument that lupus is not a single disease but many. Treatment could be individualized depending on the underlying defect generating the subtype of the disease (AU)


Assuntos
Humanos , Masculino , Feminino , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/prevenção & controle , Síndromes de Imunodeficiência/complicações , Complemento C1s/deficiência , Complemento C1q/deficiência , Complemento C1r/deficiência , Deficiência de Prolidase/complicações , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/genética , Vasculite Reumatoide/epidemiologia
12.
J Allergy Clin Immunol ; 138(1): 241-248.e3, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26936803

RESUMO

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients. OBJECTIVE: Our objective was to assess the effect of mycobacterial disease in patients with CGD. METHODS: We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria. RESULTS: Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae, or Mycobacterium ulcerans. Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients. CONCLUSION: Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD.


Assuntos
Doença Granulomatosa Crônica/complicações , Infecções por Mycobacterium/diagnóstico , Infecções por Mycobacterium/etiologia , Vacina BCG/administração & dosagem , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/etiologia , Infecções Bacterianas/mortalidade , Criança , Pré-Escolar , Feminino , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/mortalidade , Doença Granulomatosa Crônica/terapia , Humanos , Lactente , Masculino , Infecções por Mycobacterium/epidemiologia , Infecções por Mycobacterium/mortalidade , Micoses/diagnóstico , Micoses/epidemiologia , Micoses/etiologia , Micoses/mortalidade , Avaliação de Resultados da Assistência ao Paciente , Estudos Retrospectivos , Tuberculose/diagnóstico , Tuberculose/etiologia
13.
Reumatol Clin ; 12(5): 274-81, 2016 Sep-Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-26922326

RESUMO

Systemic lupus erythematosus (SLE) is a multisystemic disease with a variety of clinical presentations. Monogenic predisposing conditions to the development of this disease have been described. As examples, an impaired expression of interferon-α regulated genes or complement deficiencies have been reported in patients with SLE, with particular clinical presentations. Those defects present particular presentations and a different severity, making an argument that lupus is not a single disease but many. Treatment could be individualized depending on the underlying defect generating the subtype of the disease.


Assuntos
Genótipo , Lúpus Eritematoso Sistêmico/genética , Fenótipo , Medicina de Precisão , Marcadores Genéticos , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/terapia , Índice de Gravidade de Doença
14.
Rev Alerg Mex ; 62(1): 22-7, 2015 Jan-Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-25758110

RESUMO

BACKGROUND: Common variable immunodeficiency (CVID) implies an increased risk of cancer, with an estimated incidence of 11-13%, particularly during the 5th and 6th decade of life. B cell-Hodgkin lymphomas are the more frequent cancer, followed by non-Hodgkin lymphoma and epithelial tumors (gastric, breast, bladder and cervix). OBJECTIVE: To describe the types of cancers in a cohort of adult patients with CVID. MATERIAL AND METHOD: An observational, cross-sectional and descriptive study was made in which we reviewed the charts of patients with CVID attending the Primary Immunodeficiencies Clinic at Specialties Hospital Dr. Bernardo Sepulveda, Centro Medico Nacional Siglo XXI, Mexico City. RESULTS: There were included 23 patients with CVID diagnosis, 13 women (56%) and 10 men (44%), with an average age of 36.7 years. Four patients developed malignancies (2 men and 2 women), with a prevalence of 17.3%. The types of cancers in this group of patients were: B cell-Hodgkin lymphoma (1/23), neuroendocrine carcinoma of the pancreas (1/23), myeloid chronic leukemia (1/23) and thyroid papillary carcinoma (1/23). In two of the subjects the diagnosis of cancer was established previous to CVID diagnosis. The average age of diagnosis of cancer was 27 years (19-34 years). CONCLUSIONS: In our patients we found different types of malignancies compared to previously described. We consider necessary a screening protocol for an early diagnosis of cancer in these patients. The frequency of cancer in our population was the same as reported in the literature.

15.
Immunol Res ; 62(1): 89-94, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25752457

RESUMO

The X-linked hyper-IgM syndrome (XHIGM) is the most common form of HIGM. Patients are clinically diagnosed on the basis of recurrent sinopulmonary infections, accompanied with low levels of IgG and IgA, normal to elevated levels of IgM, and the presence of peripheral B cells. Here, we have reported a novel deletion of four nucleotides in CD40LG exon 3, c.375_378delCAAA, which led to a frameshift mutation with a premature stop codon, p.Asn101*126. The deletion resulted in a truncated protein, in which majority of the extracellular domain was lost. However, detection of surface CD40L was still possible as the intracellular, transmembrane, and part of the extracellular domains were not affected. This indicated that this mutation did not affect protein stability and that immunodetection of CD40L expression is not enough for the diagnosis of XHIGM. Our study strongly suggests that genetic diagnosis for XHIGM should always be performed when clinical data support this diagnosis and CD40L protein is present.


Assuntos
Ligante de CD40/genética , Ligante de CD40/metabolismo , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/metabolismo , Animais , Sequência de Bases , Ligante de CD40/imunologia , Células CHO , Cricetulus , Mutação da Fase de Leitura , Humanos , Lactente , Leucócitos Mononucleares , Deleção de Sequência , Transfecção
16.
Rev Alerg Mex ; 60(1): 26-30, 2013 Jan-Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-24008066

RESUMO

BACKGROUND: Common variable immunodeficiency (CVID) is one of the most common antibody deficiencies, is characterized by low serum immunoglobulins, defective antibody response and increased susceptibility to chronic and recurrent infections. OBJECTIVE: we present the clinical findings of patients with CVID in two hospitals in Mexico City. METHODS: We performed a retrospective study of patients who filled CVID criteria. We collected the following information, demographic data, age at onset, age at diagnosis, family history, infection, autoimmunity, lymphoproliferative disease, allergy, malignancy, immunoglobulin levels at diagnosis, route of administration, dosage and frequency of IVIG of each patient. Data were analyzed with descriptive statistics. RESULTS: Amongst 26 patients who filled CVID criteria, 14 were men and 12 women. The mean diagnosis delay was 48 months (22-128), serum immunoglobulins at diagnosis in mg/dL were IgG 216 (114-316), IgM 21 (12-121), IgA 21 (6-26) and IgE 4.6 (1.8) IU/mL. 81% of patients suffered pneumonia. There was a decrease in the number of pneumonias before and after treatment with gammaglobulin (p = 0.028). 27% of the patients had autoimmune diseases, 35% allergies, 35% chronic diarrhea, 62% bronchiectasis, 73% chronic cough, 50% lymphadenopathy. One patient had lymphoproliferative disease and none developed malignancy. CONCLUSIONS: We found that the delay in the diagnosis and initiation of gammaglobulin replacement affects the occurrence of complications such as bronchiectasis.


Assuntos
Imunodeficiência de Variável Comum/diagnóstico , Imunodeficiência de Variável Comum/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , México , Estudos Retrospectivos , Centros de Atenção Terciária , Saúde da População Urbana
17.
Rev Alerg Mex ; 60(1): 38-40, 2013 Jan-Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-24008068

RESUMO

Kawasaki disease is an acute, self-limiting vasculitis of unknown origin, characterized by fever, palms and soles edema, cervical lymphadenopathy, strawberry tongue, and non-exudative conjunctivitis. It is a multisystemic vasculitis that affects predominantly infants and young children. The most feared complication is the development of coronary aneurysms that occurs up to 25% of untreated patients; however there are reports of extra coronary involvement. Herein we present the case of a 2 year-old girl who had a severe symptomatology and persistent fever despite intravenous gammaglobulin. Two years later she presented right hemiparesia and headache, with data from CAT and MRI suggestive of brain mass and deviation of the midline, secondary to left frontoparietal haemorrhage that was treated with a craniotomy. She was discharged on prednisone, ASA and rehabilitation.


Assuntos
Hemorragias Intracranianas/etiologia , Síndrome de Linfonodos Mucocutâneos/complicações , Pré-Escolar , Feminino , Humanos
18.
J Clin Immunol ; 32(5): 967-74, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22665224

RESUMO

PURPOSE: To evaluate the lipopolysaccharide (LPS)-induced pro-inflammatory cytokine response by peripheral blood mononuclear cells (PBMCs) from XLA patients. METHODS: Thirteen patients with XLA were included in the study. LPS-induced TNF-α, IL-1ß, IL-6, and IL-10 production was determined in PBMCs from patients and matched healthy controls by ELISA. Cytokine production was correlated with the severity of mutation, affected domain and clinical characteristics. RESULTS: In response to LPS, PBMCs from XLA patients produced significantly higher amounts of pro-inflammatory cytokines and IL-10 compared to controls, and this production was influenced neither by the severity of the mutation nor the affected domain. PBMCs from patients with a history of more hospital admissions before their diagnosis produced higher levels of TNF-α. PBMCs from patients with lower serum IgA levels showed a higher production of TNF-α and IL-1ß. Less severe (punctual) mutations in the Btk gene were associated with higher serum IgG levels at diagnosis. CONCLUSIONS: Our results demonstrate a predominantly inflammatory response in XLA patients after LPS stimulation and suggest a deregulation of TLR signaling in the absence of Btk. This response may be influenced by environmental factors.


Assuntos
Agamaglobulinemia/imunologia , Citocinas/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Leucócitos Mononucleares/imunologia , Proteínas Tirosina Quinases/genética , Adolescente , Adulto , Tirosina Quinase da Agamaglobulinemia , Agamaglobulinemia/genética , Linfócitos B/imunologia , Estudos de Casos e Controles , Células Cultivadas , Criança , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Lipopolissacarídeos/imunologia , Masculino , Mutação , Proteínas Tirosina Quinases/imunologia , Receptor 4 Toll-Like/imunologia , Adulto Jovem
19.
Rev Alerg Mex ; 59(1): 37-40, 2012 Jan-Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-24007932

RESUMO

Henoch-Schönlein Purpura (HSP) and Kawasaki disease (KD) are the most frequent systemic vasculitis in childhood. Both diseases are clearly distinct and easily distinguishable. Despite their high frequency, the coexistence of both diseases in the same patient is very rare. The diagnosis of these two diseases is based on clinical features, but sometimes it may be difficult, since signs and symptoms can be atypical and occasionally there are overlapping features among different forms of vasculitis. We present a 5 year-old boy who showed KD and three years later he developed HSP. We discuss similarities and differences between these two systemic vasculitic diseases and make a review of the literature of the few cases reported where KD and PHS have coexisted. Although rare, these two diseases can be present in the same patient and should be treated accordingly.


Assuntos
Síndrome de Linfonodos Mucocutâneos , Púrpura de Schoenlein-Henoch , Humanos , Vasculite Sistêmica , Vasculite
20.
Rev Alerg Mex ; 59(2): 93-6, 2012 Apr-Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-24007965

RESUMO

Down syndrome is associated with changes characteristic of primary immunodeficiencies, such as susceptibility to infection, autoimmunity and malignancy risk. However, it is not considered a primary immunodeficiency but rather a syndromatic deficiency, due to the relevance of the characteristic neurological delay. This article presents some arguments that consider Down syndrome as a primary immunodeficiency.


Assuntos
Síndrome de Down , Síndromes de Imunodeficiência , Autoimunidade , Humanos
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