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2.
Clin Immunol ; 213: 108366, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32092471

RESUMO

The nuclease Artemis is a enzyme for V(D)J recombination allowing for the creation of T and B lymphocytes as well as for the repair of radiation-induced DNA double strand breaks encoded by the DCLRE1C gene. Artemis-null mutations are a known cause of severe combined immunodeficiencies (SCIDs) with radiosensitivity. Hypomorphic mutations in Artemis have been reported to cause a "leaky SCID"" phenotype, typically with hypogammaglobulinemia. We present four patients, all harboring the same unique hypomorphic mutation in the DCLRE1C gene, an 8-base pair insertion (c.1299_1306dup, p.Cys436*) presenting with a relatively mild phenotype including pulmonary infectious EBV-related lymphoproliferative diseases, an autoimmune phenomenon. Non-typical findings of IgG hypergammaglobulinemia accompanied by IgA and IgE deficiency were recorded in all patients. The typical viral, fungal, and opportunistic infections were absent, and patients reached a relatively old age.


Assuntos
Proteínas de Ligação a DNA/genética , Endonucleases/genética , Hipergamaglobulinemia/genética , Imunoglobulina G , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/imunologia , Adolescente , Doenças Autoimunes/genética , Feminino , Humanos , Deficiência de IgA/genética , Imunoglobulina E/deficiência , Transtornos Linfoproliferativos/genética , Masculino , Mutação , Fenótipo , Imunodeficiência Combinada Severa/complicações
3.
Ann Dermatol Venereol ; 147(2): 131-134, 2020 Feb.
Artigo em Francês | MEDLINE | ID: mdl-31973905

RESUMO

BACKGROUND: Severe combined immunodeficiency (SCID) is a the most severe form of primary immunodeficiency and is highly heterogeneous. We report an atypical form of SCID revealed by exfoliative erythroderma. PATIENTS AND METHODS: A 3-month-old boy, born to consanguineous parents, was admitted to the dermatology department with exfoliative erythroderma associated with eczematous patches and alopecia of the scalp, eyelashes, and eyebrows, but with no lymphadenopathy or hepatosplenomegaly. He displayed chronic diarrhea and recurrent infection since birth. A complete blood count showed marked leukocytosis with eosinophilia and lymphocytosis. These clinical and biological findings improved partly with topical steroids. The patient no longer had erythroderma and showed regrowth of hair, eyelashes and eyebrows. The subsequent CBC showed less marked eosinophilia with mild lymphopenia and no leukocytosis. Immunoglobulin levels were undetectable. Primary immunodeficiency was discussed. Immunological investigations concluded on a diagnosis of T-B-NK+ SCID. Mutation analysis revealed a homozygous c.1338C>G (pCys446Trp) mutation in the RAG2 gene. Hematopoietic stem cell transplantation is planned in the near future. CONCLUSION: This case illustrates atypical T-B-NK+ SCID revealed by severe exfoliative erythroderma in a 3-month-old boy with RAG2 gene mutation. Neonatal erythroderma must be considered a warning sign of primary immunodeficiency requiring immediate immunological phenotyping as well as genetic testing for a definitive diagnosis.


Assuntos
Dermatite Esfoliativa/etiologia , Imunodeficiência Combinada Severa/complicações , Alopecia/etiologia , Alopecia/patologia , Doença Crônica , Consanguinidade , Proteínas de Ligação a DNA/genética , Dermatite Esfoliativa/patologia , Diarreia/etiologia , Eczema/etiologia , Eczema/patologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Masculino , Proteínas Nucleares/genética , Fotografação , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/terapia
4.
Pediatr Infect Dis J ; 39(3): 258-259, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31876612

RESUMO

We are reporting a case of Bacillus Calmette-Guérin vaccine-disseminated infection in a 19-month-old HIV-negative girl diagnosed with severe combined immunodeficiency. While standard culture protocols failed to isolate and culture the Mycobacterium bovis Bacillus Calmette-Guérin strain, it was isolated from skin and mesenteric lymph node biopsies using the shell-vial assay, allowing whole-genome sequencing and in silico drug susceptibility testing.


Assuntos
Testes de Sensibilidade Microbiana/métodos , Mycobacterium bovis , Imunodeficiência Combinada Severa/complicações , Tuberculose/diagnóstico , Tuberculose/etiologia , Antituberculosos/uso terapêutico , Biópsia , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/métodos , Quimioterapia Combinada , Feminino , Humanos , Lactente , Linfonodos/microbiologia , Linfonodos/patologia , Mycobacterium bovis/efeitos dos fármacos , Mycobacterium bovis/genética , Mycobacterium bovis/imunologia , Imunodeficiência Combinada Severa/terapia , Úlcera Cutânea/etiologia , Úlcera Cutânea/patologia , Resultado do Tratamento , Tuberculose/tratamento farmacológico
5.
Pediatr Dermatol ; 36(5): 672-676, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31309596

RESUMO

Bacille Calmette-Guérin (BCG), a live attenuated vaccine prepared using Mycobacterium bovis, can prevent tuberculosis in children and is routinely administered to infants in China and many other countries. A serious complication following vaccination is disseminated BCG infection. The risk is greatly increased in patients with severe combined immunodeficiency disease (SCID), a syndrome characterized by deficiency of both humoral and cellular immunity. We report a case of disseminated BCG infection in an infant with SCID caused by two novel janus kinase 3 (JAK3) gene mutations.


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Vacina BCG/efeitos adversos , Janus Quinase 3/genética , Mutação/genética , Imunodeficiência Combinada Severa/complicações , Tuberculose/etiologia , Feminino , Humanos , Lactente , Mycobacterium bovis , Imunodeficiência Combinada Severa/genética
6.
Infect Dis (Lond) ; 51(8): 585-592, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31204539

RESUMO

Background: Bacille Calmette-Guerin (BCG) is included in the routine vaccination program in Gaza and the West Bank. Although safe, complications can occur and include local, extra-regional and disseminated BCG infection. Therefore it is contraindicated in immunodeficiencies. However, most infants are immunized prior to diagnosis of immunodeficiency. We report clinical and immunological characteristics of patients referred with severe combined immunodeficiency (SCID) who suffered from BCG complications. Methods: Files of patients referred for evaluation of immunodeficiency from January 2008 to February 2016 were retrieved. All patients have received BCG. Cell surface markers of peripheral blood mononuclear cells (PBMCs) were measured by immunofluorescent staining and flow cytometry. Serum concentrations of immunoglobulins were measured using nephelometry. Genetic diagnosis of SCID was made by direct Sanger sequencing of candidate genes. BCG complications were classified as: a) local; b) regional; c) distant; and d) disseminated disease. Results: Twenty-one children were diagnosed with SCID. BCG complications were diagnosed in 12 (57.1%). Eight patients developed local and regional disease (67%) and 4 (33%) had disseminated infection. Patients received at least three drugs: isoniazid, ethambutol and rifampicin. Outcome was relatively favorable with eight patients surviving (66.6%). No death related to BCG infection was observed. Disseminated disease was associated with reduced numbers of total lymphocytes, CD3 and CD8 levels (p < .05). Conclusions: Although high rates of BCG complications were observed, mortality was not increased and outcomes were good. Increased awareness in countries where BCG vaccine is not routinely administered and newborn screening programs for SCID could reduce complication rates.


Assuntos
Vacina BCG/efeitos adversos , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/microbiologia , Tuberculose/etiologia , Vacinação/efeitos adversos , Antibacterianos/uso terapêutico , Anticorpos Antibacterianos/sangue , Criança , Pré-Escolar , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Leucócitos Mononucleares , Masculino , Oriente Médio , Mycobacterium bovis , Tuberculose/tratamento farmacológico
7.
BMJ Case Rep ; 12(5)2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151968

RESUMO

Severe combined immunodeficiency (SCID) is an extremely rare disease caused by a disruption in the forkhead box N1 (FOXN1) gene, with an incidence of <1 per 1 000 000 live births. We report a boy aged 4 months who presented with a history of fever for 3 weeks and enlarged lymph nodes. The fever was associated with dry cough and runny nose. On physical examination, we noted oral thrush, generalised lymphadenopathy, nail dystrophy and alopecia. Flow cytometry of lymph node biopsy showed high-grade B-cell lymphoma. In addition, Epstein-Barr virus (EBV) infection was documented by PCR. The diagnosis of SCID was made by genetic testing, which revealed a homozygous variant of the FOXN1 gene. The variant was confirmed with Sanger sequencing. Management of EBV infection and lymphoma was initiated; unfortunately, the patient passed away on day 45 of hospitalisation.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Fatores de Transcrição Forkhead/deficiência , Linfoma de Células B/complicações , Imunodeficiência Combinada Severa/complicações , Diagnóstico Diferencial , Infecções por Vírus Epstein-Barr/diagnóstico , Evolução Fatal , Fatores de Transcrição Forkhead/genética , Herpesvirus Humano 4 , Humanos , Lactente , Masculino , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/genética
8.
Rev Peru Med Exp Salud Publica ; 36(1): 134-137, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31116327

RESUMO

The Bacillus Calmette-Guerin (BCG) vaccine given to newborns in countries with a high incidence of tuberculosis may cause local reactions up to disseminated infection in immunocompromised patients. We report the case of a six-monthold male infant with a history of having received the BCG vaccine at birth, and presenting repeated infectious, soft violet nodules in the trunk and extremities with the presence of acid-alcohol-resistant bacilli (BAAR) in histopathology and skin culture; the molecular study reported the presence of Mycobacterium bovis BCG. In the tomography, interstitial opacities were observed in the lungs and in the gastric lavage BAAR was identified. The genetic study of the patient and the mother revealed the presence of a mutation in the IL2RG gene confirming the diagnosis of severe combined immunodeficiency. Received treatment with human immunoglobulin and anti-tuberculosis scheme with isoniazid, rifampicin, and ethambutol. We present the case because of the implication in the life prognosis of these patients and because of the need for an accurate and timely diagnosis.


Assuntos
Vacina BCG/efeitos adversos , Imunodeficiência Combinada Severa/complicações , Tuberculose/etiologia , Humanos , Lactente , Masculino , Tuberculose/microbiologia
10.
J Eur Acad Dermatol Venereol ; 33(7): 1412-1420, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30869812

RESUMO

BACKGROUND: Paediatric cutaneous granuloma with primary immunodeficiency (PID) is a rare condition. The physiopathology is unclear, and treatment is challenging. We report on 17 paediatric cases and review the literature. OBJECTIVES: To make dermatologists and dermatopathologists aware of the diagnostic value of skin granulomas in paediatric PID. METHODS: We collected data on 17 patients with cutaneous granulomas and PID registered with us and also reviewed 33 cases from the literature. RESULTS: Cutaneous granuloma was the presenting feature of the PID in 15 of the 50 collated cases. The lesions presented as red-brownish nodules and infiltrated ulcerative plaques, predominantly on the face and limbs. Scleroderma-like infiltration on a single limb was observed in 10% of the cases. The associated PID was ataxia-telangiectasia (52%), combined immunodeficiency (24%), cartilage-hair hypoplasia (6%) and other subtypes (18%). The granulomas were mostly sarcoidal, tuberculoid, palisaded or undefined subtypes. In some patients, several different histopathologic granulomatous patterns were found in the same biopsy. Some granulomas were associated with the presence of a vaccine strain of rubella virus. CONCLUSION: Cutaneous granulomas associated with a PID have a variable clinical presentation. A PID can be suspected when crusty, brownish lesions are found on the face or limbs. The concomitant presence of several histological subtypes in a single patient is suggestive of a PID.


Assuntos
Granuloma/diagnóstico , Granuloma/patologia , Doenças da Imunodeficiência Primária/diagnóstico , Dermatopatias/diagnóstico , Dermatopatias/patologia , Anormalidades Múltiplas/diagnóstico , Ataxia Telangiectasia/etiologia , Criança , Pré-Escolar , Feminino , Granuloma/complicações , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Humanos , Hidrocolpos/complicações , Hidrocolpos/diagnóstico , Lactente , Masculino , Polidactilia/complicações , Polidactilia/diagnóstico , Doenças da Imunodeficiência Primária/complicações , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/diagnóstico , Dermatopatias/complicações , Úlcera Cutânea/etiologia , Doenças Uterinas/complicações , Doenças Uterinas/diagnóstico
11.
Indian J Pediatr ; 86(7): 584-589, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30879237

RESUMO

OBJECTIVES: Severe combined immunodeficiency (SCID) represents one of the most severe forms of Primary immunodeficiency (PID) disorders, characterized by T cell lymphopenia (TCL) and lack of cellular and humoral immune responses. However, not all patients with low T cell lymphocyte counts may have an abnormal T cell immunity and the observed TCL may be a temporary suppression resulting from transient lymphopenia secondary to severe infections. In such cases, it is necessary to estimate the severity of the observed TCL by assessing thymic capabilities. METHODS: In this study, patients clinically suspected of SCID were evaluated for lymphocyte subsets analysis, naïve T cells and T cell receptor excision circles (TREC). RESULTS: Patients with transient lymphopenia had detectable TREC levels and normal naïve T cells subsets. Normalization of absolute lymphocyte counts, and T cells was seen in the patients after a short duration. CONCLUSIONS: The authors highlight the importance of detailed immunological investigations in an infant with severe infections and lymphopenia before labeling the infant as SCID.


Assuntos
Linfopenia/complicações , Linfopenia/imunologia , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/imunologia , Feminino , Humanos , Imunidade Humoral , Lactente , Contagem de Linfócitos , Masculino
13.
Clin Immunol ; 200: 16-18, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30630113

RESUMO

Severe combined immunodeficiency (SCID) can be caused by deleterious mutations in DCLRE1C, leading to deficient non-homologous end joining by compromising the function of the Artemis protein. This impairs the process of V(D)J recombination of the T- and B-cell receptors and typically results in radiosensitive T-, B-, NK+ SCID presenting during the first months of life. We present a case of a 3-year-old girl with two novel compound heterozygous variants in DCLRE1C (c.58G>C and c.374A>C) that were associated with marked reduced numbers of peripheral T- and B-cells and undetectable total serum IgG. Despite the severe laboratory phenotype, the patient had a normal development, albeit failure to thrive (-2.5 to -3 SD), during her first years of life including day-care attendance at preschool for 1.5 years. After being diagnosed with pneumonia the clinical picture of SCID was recognized and the girl successfully underwent hematopoietic stem-cell transplantation.


Assuntos
Agamaglobulinemia/genética , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Imunodeficiência Combinada Severa/genética , Agamaglobulinemia/complicações , Agamaglobulinemia/imunologia , Pré-Escolar , Feminino , Heterozigoto , Humanos , Mutação , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/etiologia , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/imunologia
14.
J Pediatr ; 204: 219-224.e1, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30268402

RESUMO

OBJECTIVE: Based on experiences and results from newborn screening for severe combined immunodeficiency (SCID), we evaluated the occurrence of chromosome 22q11.2 deletion syndrome (22q11.2DS) in newborns with different T cell receptor excision circles (TREC) results and established a second tier genetic test for 22q11.2DS. STUDY DESIGN: Recalled dried blood spots from 486 newborns with TREC results <90 copies/uL were tested from the SCID newborn screening. Quantitative real-time polymerase chain reaction assay was used to detect the copy number of TBX1 and HIRA genes by simple DNA extraction method. Multiplex ligation dependent probe amplification was used for further confirmation. RESULTS: Four hundred sixty-eight cases were considered negative because their haploid copy number of TBX1 and HIRA genes was >0.75. Eighteen cases with TBX1 and/or HIRA gene copy number <0.75 were suspected as positive, and 13 cases were further confirmed with 22q11.2DS. Detection rates of 22q11.2DS were 10.7% (6/56) in TREC <30 copies, 6.8% (9/132) in <50 TREC copies, 4.6% (12/260) in <70 TREC copies, and 2.7% (13/486) in <90 TREC copies. CONCLUSIONS: 22q11.2DS detection can be incorporated into the second-tier assay in subjects with low TREC copies in SCID screening. The dried blood spot methods were feasible for 22q11.2DS newborn screening.


Assuntos
Síndrome de DiGeorge/genética , Triagem Neonatal/métodos , Receptores de Antígenos de Linfócitos T/genética , Imunodeficiência Combinada Severa/genética , Proteínas de Ciclo Celular/genética , Síndrome de DiGeorge/complicações , Teste em Amostras de Sangue Seco/métodos , Feminino , Chaperonas de Histonas/genética , Humanos , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase Multiplex , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Imunodeficiência Combinada Severa/complicações , Proteínas com Domínio T/genética , Fatores de Transcrição/genética
15.
Pediatr Infect Dis J ; 38(2): 157-160, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29613974

RESUMO

Newborn screening for severe combined immunodeficiency using T-cell receptor excision circles allows prompt diagnosis and initiation of supportive and curative therapy thereby reducing morbidity and mortality. However, profound combined immunodeficiencies with normal numbers of nonfunctional T cells will go undetected. We present a patient with calcium release-activated calcium channel gene (ORAI1) deficiency and normal T-cell receptor excision circle numbers observed after diagnosis at the age of 14 months who suffered from disseminated fatal cytomegalovirus and Pneumocystis jirovecii infection, demonstrating a potential pitfall of the current newborn screening program.


Assuntos
Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/isolamento & purificação , Testes Diagnósticos de Rotina/métodos , Triagem Neonatal/métodos , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Imunodeficiência Combinada Severa/diagnóstico , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/patologia , Evolução Fatal , Feminino , Humanos , Lactente , Recém-Nascido , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/patologia , Imunodeficiência Combinada Severa/complicações , Linfócitos T/patologia
16.
Rev Chil Pediatr ; 90(6): 581-588, 2019 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-32186580

RESUMO

Primary immunodeficiencies (PIDs) are a set of about 350 genetic disorders that affect the normal function of the immune system. Advances in genetic diagnosis have allowed the description of new defects in the immune system, broadening the clinical spectrum of PIDs' manifestations beyond susceptibility to infection. Although most PIDs present with recurrent or opportunistic infections, a subgroup of them may be recognized by the early development of auto-inflammatory events, tumors and, paradoxically, the coexistence of autoimmunity and immunodeficiency in the same patient. As their clinical manifestations, the severity of PIDs is highly variable. Severe combined immunodefi ciency (SCID), a PID that affects cellular and humoral immunity, is one of the most severe forms of PIDs and the only available curative treatment in Latin America is hematopoietic stem cells trans plantation. All patients affected by SCID die during the first two years of life if they are not diagnosed and treated opportunely. In contrast, early transplantation of patients with SCID can lead to excellent survival outcomes. Despite recent advances in the diagnosis of PIDs in Chile, diagnostic resources are not available throughout the country, making the early diagnosis of SCID and other forms of PID difficult in big areas of Chile. The objective of this article is to review general concepts on the patho physiology, diagnosis, and initial management of SCID and raise the need for the implementation of neonatal screening for SCID in Chile.


Assuntos
Diagnóstico Precoce , Triagem Neonatal , Imunodeficiência Combinada Severa/diagnóstico , Chile/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Recém-Nascido , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/epidemiologia , Imunodeficiência Combinada Severa/terapia
17.
Rev Chil Pediatr ; 90(6): 668-674, 2019 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-32186591

RESUMO

Patients with Primary Immunodeficiencies (PID) are at a higher risk of developing severe morbidities and mortality due to the administration of BCG vaccine. Risk-to-benefit of universal BCG vaccina tion of newborns must be assessed periodically. Chile has a low incidence of tuberculosis (TB) but the local epidemiology has recently changed with an increase of TB cases. Changes in the BCG vaccine schedule have been made in countries with similar or higher TB incidences and lower BCG vaccine coverage, with no increase in the severe TB cases, which are prevented by BCG. These changes have prevented serious complications in PID patients. We propose a critical analysis of the BCG adminis tration date in Chile due to the technical possibility of performing neonatal PID screening.


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Vacina BCG/efeitos adversos , Doenças da Imunodeficiência Primária/complicações , Chile/epidemiologia , Contraindicações de Medicamentos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Esquemas de Imunização , Incidência , Lactente , Recém-Nascido , Imunodeficiência Combinada Severa/complicações , Tuberculose/epidemiologia , Tuberculose/prevenção & controle
19.
Pediatrics ; 142(5)2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30377239

RESUMO

Deficiency of adenosine deaminase 2 (DADA2) is a rare autoinflammatory disease that was firstly described in patients with early-onset strokes, livedo reticularis, and periodic fever resembling polyarteritis nodosa. In reported case series, researchers described highly variable manifestations, including autoimmunity, immunodeficiency, hepatosplenomegaly, pancytopenia, ichthyosiform rash, and arthritis, in patients with DADA2. A thirteen-year-old female patient who was born to consanguineous parents was admitted to our hospital with generalized edema and leg pain. A physical examination revealed splenomegaly and left knee arthritis. Nephrotic-range proteinuria and hypoalbuminemia were present, and a renal biopsy revealed amyloidosis. Despite the absence of periodic fever and livedo reticularis, our patient had suggestive features of DADA2, including low serum immunoglobulin G and immunoglobulin M levels, hepatosplenomegaly, and renal amyloidosis. We found a heterozygote Met694Val mutation in the Mediterranean fever gene and a novel homozygote Thr317Argfs*25 (c.950-950delCys) mutation in the cat eye chromosome region 1 gene. A functional analysis revealed absent plasma adenosine deaminase 2 activity. Canakinumab was administered because of unresponsive proteinuria despite 2 months of treatment with colchicine and methylprednisolone. Proteinuria improved after 7 doses of canakinumab. In conclusion, DADA2 should be considered in the differential diagnosis of renal amyloidosis, particularly in the absence of homozygote Mediterranean fever mutations. Although anti-tumor necrosis factor agents are widely offered in DADA2 treatment, we speculate that canakinumab may be an appropriate treatment of renal amyloidosis in DADA2.


Assuntos
Amiloidose/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Nefropatias/tratamento farmacológico , Imunodeficiência Combinada Severa/complicações , Adenosina Desaminase/genética , Adolescente , Amiloidose/etiologia , Anticorpos Monoclonais Humanizados , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Nefropatias/etiologia , Mutação
20.
Papillomavirus Res ; 6: 83-89, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30414951

RESUMO

Canine oral papillomavirus (CPV1, also known as COPV), the most common cause of non-neoplastic papillomas, has not been shown to cause squamous cell carcinomas (SCC). Furthermore, malignant transformation of benign papillomas to SCC has only been reported in a single group of dogs with severe combined immunodeficiency infected with CPV2. Here, we report a series of 7 dogs with benign CPV1-associated papillomas with histologic evidence of CPV1 causing malignant transformation to carcinoma in situ and ultimately SCC. Expression of p53 and p16 proteins in CPV1-infected cells within the benign papillomas and lesions that progressed into SCC also supported an association between papillomavirus and malignant transformation. Moreover, our retrospective analysis indicated that while there have been increased numbers of viral papillomas with malignant transformation, the number of annually diagnosed canine viral papillomas has remained constant over the past decade in our laboratory. We speculate that either an altered host immunity from increased usage of immunosuppressive drugs or changing environmental factors, e.g. increase exposure to UV radiation, may cause an increased oncogenic potential of this "low-risk" virus. This study aims to raise awareness of the malignant potential of CPV1 and to encourage further investigations into the cause of this suspected change in its oncogenic potential.


Assuntos
Carcinoma de Células Escamosas/veterinária , Doenças do Cão/patologia , Lambdapapillomavirus/isolamento & purificação , Neoplasias Bucais/veterinária , Papiloma/veterinária , Infecções por Papillomavirus/veterinária , Animais , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Doenças do Cão/virologia , Cães , Histocitoquímica , Imuno-Histoquímica , Microscopia , Neoplasias Bucais/patologia , Neoplasias Bucais/virologia , Papiloma/complicações , Papiloma/virologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Estudos Retrospectivos , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/veterinária
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