FAN · 5,0% na cistite intersticial 1,7% em Graves 6,0% em Hashimoto.. Mahler M, Parker T, Peebles...
Transcript of FAN · 5,0% na cistite intersticial 1,7% em Graves 6,0% em Hashimoto.. Mahler M, Parker T, Peebles...
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FAN
FAN é feito por IFI há mais de 60 anos
(1950 by Coons and Kaplan)
Termo tem gerado confusão
Acs Anti-celular termo mais apropriado
Anti-nucleo (constituintes)
Anti-nucleo (envelope nuclear)
Anti-citosol (proteínas citosólicas)
Anti-citoplasma (organelas citoplasmáticas)
Solomon DH, Kavanaugh AJ, Schur PH. Evidence-based guidelines for the use of immunologic tests: antinuclear antibody testing.
Arthritis Rheum 2002;47:434–44.
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FAN
Acs específicos podem aparecer anos antes dos sintomas clínicos
Presente em doenças autoimunes
Triagem
Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the
clinical onset of systemic lupus erythematosus. N Engl J Med 2003; 349:1526–33.
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FAN
Técnica de Imunofluorescência Indireta
Células HEp-2
Série de diluições do soro até o final
Determinação visual da positividade e padrão
Determinação do antígeno específico
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IV Brazilian guidelines
for autoantibodies on
HEp-2 cells.
Francescantonio PL, et al.
Rev Bras Reumatol. 2014
Jan-Feb;54(1):44-50.
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Exemplo de laudo descritivo conforme as
recomendações do IV consenso (2014),
apresentando-se como primeira informação a
definição do padrão.
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FAN
FATORES QUE INFLUENCIAM
Onde o exame foi realizado
Leitura da fluorescência (subjetividade)
Exige treinamento e experiência
Variabilidade de resultados
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FAN
Alta variação na leitura dos testes entre países europeus e mesmo
dentro do mesmo País (2014)
No Brasil, estudo feito em 2013 analisou 17 padrões
Reações e leitura feitos de forma cega e independente por três
centros diagnósticos.
Evidenciou-se boa reprodutibilidade dos 17 padrões testados
Damoiseaux J1, Agmon-Levin N, Van Blerk M,et al.From ANA-screening to antigen-specificity: an EASI-survey on the daily practice in
European countries. Clin Exp Rheumatol. 2014 Jul-Aug;32(4):539-46.
Dellavance A, Cruvinel W de M, Francescantonio PLC, Mangueira CLP, Drugowick IC, Rodrigues SH, et al. Variability in the recognition of
distinctive immunofluorescence patterns in different brands of HEp-2 cell slides. J Bras Patot Med Lab. 2013;49(3):182-90.
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FAN
Especificidade do exame depende:
Diluição inicial
Titulo encontrado
Padrão
População estudada
Idade
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FAN E FATOR REUMATÓIDE EM IDOSOS DE CURITIBA-PR
Table - IgM-RF and ANA positivity according to age in studied groups
Age
(years)
n=336 Positive RF*
(22/336)
Positive ANA**
(58/336)
≤50 56 16.6% 2/56 3.6% 1/56 1.8%
51 - 60 51 15.2% 3/51 5.9% 5/51 9.8%
61 - 70 120 35.7% 6/120 5.0% 27/120 22.5%
71 - 80 79 23.5% 6/79 7.6% 19/79 24.0%
> 81 30 8.9% 5/30 16.6% 6/30 20.0%
Nisihara R, Kubis MM, Rodrigues PC, Skare T et al. Antinuclear antibodies and rheumatoid factor positivity in healthy elderly adults: a cross-
sectional study in 336 individuals. J Am Geriatr Soc. 2013 Nov;61(11):2044-6
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Nisihara R, Kubis MM, Rodrigues PC, Skare T et al. Antinuclear antibodies and rheumatoid factor positivity in healthy elderly adults: a cross-
sectional study in 336 individuals.J Am Geriatr Soc. 2013 Nov;61(11):2044-6
FAN E FATOR REUMATÓIDE EM IDOSOS DE CURITIBA-PR
Maioria dos casos positivos:
título 1:80 e
padrão granular fino denso-
DFS)
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FAN – PADRÃO DFS
Ac anti DFS 70 feito por IFI foi positivo em até 33% pessoas sadias,
MAS não é encontrado em
pacientes com doenças reumáticas
sistêmicas.
Mahler M1, Hanly JG, Fritzler MJ.
Importance of the dense fine speckled pattern on HEp-2 cells and anti-DFS70 antibodies for the
diagnosis of systemic autoimmune diseases. Autoimmun Rev. 2012 Jul;11(9):642-5.
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Ac ANTI DSF70
n = 3263 sadios - Ac anti DFS70 por ELISA
251 pacientes com LES
8,9% em indivíduos saudáveis
2,8% no LES,
2,6% na artrite reumatóide
4,0% na asma
5,0% na cistite intersticial
1,7% em Graves
6,0% em Hashimoto..
Mahler M, Parker T, Peebles CL et al. Anti-DFS70 antibodies are more prevalent in healthy individuals compared to patients
with systemic autoimmune rheumatic diseases. J Rheumatol. 2012 Nov;39(11):2104-10
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Novos métodos de imunoadsorção de Ac anti-DFS70
Aumentar a especificidade do FAN
Ac ANTI DSF70
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FAN
Aumento no número de solicitações
Teste presente no check-up
Tentativas de outras técnicas laboratoriais como
ELISA
quimioluminescência,
fluorimetria...
Kivity S, Gilburd B, Agmon-Levin N, et al. A novel automated indirect
immunofluorescence autoantibody evaluation. Clin Rheumatol 2012;31:503–9.
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NOVAS METODOLOGIAS PARA O FAN
Uso de Antígenos sintéticos
Não dão os mesmos resultados
Poderiam ser complementares ?
American College of Rheumatology – gold standard - IFI
O IV Consenso não recomenda a utilização de ensaios
automatizados na triagem de autoanticorpos
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FAN
Estudo de coorte (n=1306 consultas) onde 232 pacientes
foram encaminhados ao reumatologista por FAN positivo
(solicitado por pediatra, obstetra, clinico-geral)
A razão mais comum para solicitação do FAN: dor
generalizada.
The clinical utility of a positive antinuclear antibody test result.
Abeles AM, Abeles M.
Am J Med. 2013 Apr;126(4):342-8. doi:
10.1016/j.amjmed.2012.09.014. Epub 2013 Feb 8
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FAN
5/232 confirmaram LES (VPP= 2,1%)
23/232 tinham outra doença reumática associada ao
FAN (VPP 9,1%)
Nenhuma doença reumática associada tinha título
menor que 1:160
The clinical utility of a positive antinuclear antibody test result.
Abeles AM, Abeles M.
Am J Med. 2013 Apr;126(4):342-8. doi: 10.1016/j.amjmed.2012.09.014. Epub 2013 Feb 8
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NO ENTANTO,
Autores não levaram em consideração baixo título inicial
Não consideraram padrão
Outras doenças não reumáticas não foram pesquisadas.
Meroni PL1, Chan EK, Tincani A, García de la Torre I, Andrade LE. Antinuclear antibody test: when to
order? Am J Med. 2013 Oct;126(10):e17. doi: 10.1016/j.amjmed.2013.04.022.
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FAN
Pode ser precursor da doença
Exame de baixo custo
0,05% (1/2000) pessoas pode ter LES – triagem e diagnóstico precoce
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FAN – PONTO DE CORTE
Estudo internacional demonstra
FAN 1:40 em 31,7% das pessoas sadias
FAN 1:80 em 13,3%
FAN 1:160* em 5% do grupo sadio
Importância do padrão de positividade
*Considerar perda de sensibilidade
Crianças: não há consenso.
Tan EM, Feltkamp TE, Smolen JS, et al. Range of antinuclear
antibodies in“healthy” individuals. Arthritis Rheum 1997;40:1601–11.
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FAN
FAN negativo – Anti-ds dNA negativo
FAN negativo – Anti Ro (SSA) positivo
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FAN
É importante para diagnóstico de DAÍ
Ampla discussão sobre seu uso
Recomendações para sua execução e interpretação
Necessidade de treinamento para os executores dos exames
Educação continuada para os solicitantes dos exames.
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PONTOS CHAVES
Triagem
Interpretação do resultado
Outros exames mais específicos
Sm, RNP, Ro,La, Jo-1, Scl-70
Anti-dsDNA
Anti-p ribossomal
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FAN – PROGNÓSTICO DE LES EM PACIENTES TRATADOS COM IMUNOBIOLÓGICOS
n=1000 pacientes com AR
n= 454 em uso de imunobiológicos
Infliximab = 31,7% FAN pos
Adalimumab = 16,1% FAN pos
Etanercept= 11,8% FAN pos
.
Takase et al,. What is the utility of routine ANA testing in predicting development of biological
DMARD-induced lupus and vasculitis in patients with rheumatoid arthritis? Data from a single-
centre cohort. Ann Rheum Dis 2014 Sep;73(9):1695-9. doi: 10.1136/annrheumdis-2014-205318.
Epub 2014 May 22
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FAN
Não se observou utilidade em série de testes FAN / dsDNA para
prever o o desenvolvimento de lúpus / vasculite.
Sugeriu que pacientes que fazem FAN positivo podem apresentar
ausência de resposta secundária à terapia com imunobiológicos
.
Takase et al,. What is the utility of routine ANA testing in predicting development of biological
DMARD-induced lupus and vasculitis in patients with rheumatoid arthritis? Data from a single-
centre cohort. Ann Rheum Dis 2014 Sep;73(9):1695-9. doi: 10.1136/annrheumdis-2014-205318.
Epub 2014 May 22