Espondilite anquilosante e uveíte: revisão / Ankylosing spondylitis and uveitis: overview

O presente trabalho propõe uma revisão de epidemiologia, patogênese, quadro clínico, diagnóstico e tratamento da espondilite anquilosante e sua associação com alteração ocular com a devida condução da doença e suas manifestações. Os autores utilizaram em sua pesquisa os bancos de dados PubMed (MEDLINE), LILACS e Biblioteca do Centro de Estudos de Oftalmologia. A espondilite anquilosante é uma doença inflamatória crônica que acomete preferencialmente o esqueleto axial, podendo evoluir com rigidez e limitação funcional progressiva. Seu início costuma ocorrer por volta da segunda à terceira década de vida, preferencialmente em indivíduos do gênero masculino, caucasianos e HLA-B27-positivos. Sua etiologia e patogênese não são completamente elucidadas, e seu diagnóstico costuma ser tardio. O controle clínico e o tratamento são frequentemente satisfatórios.A uveíte anterior aguda é a manifestação extra-articular mais comum, ocorrendo em cerca de 20%-30% dos pacientes com espondilite anquilosante. Aproximadamente metade dos casos de uveíte anterior aguda está associada à presença do antígeno HLA-B27, podendo ser a primeira manifestação de uma doença reumatológica não diagnosticada, geralmente com boa resposta terapêutica e bom prognóstico. Concluímos que, para melhor avaliação e tratamento dos pacientes com uveíte, é importante maior integração entre oftalmologistas e reumatologistas.

The present article reviews the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of ankylosing spondylitis and its association with ocular changes. The authors used the PubMed (MEDLINE), LILACS, and Ophthalmology Library databases. Ankylosing spondylitis is a chronic inflammatory disease that usually affects the axial skeleton and can progress to stiffness and progressive functional limitation. Ankylosing spondylitis usually begins around the second to third decade of life, preferentially in HLA-B27-positive white males. Its etiology and pathogenesis are not completely understood, and its diagnosis is diffi cult. Clinical control and treatment are frequently satisfactory. Acute anterior uveíte is the most common extra-articular manifestation, occurring in 20%-30% of the patients with ankylosing spondylitis. Approximately half of the acute anterior uveíte cases are associated with the presence of the HLA-B27 antigen. It can be the first manifestation of an undiagnosed rheumatic disease, usually having a good prognosis and appropriate response to treatment. In conclusion, for better assessment and treatment of patients with uveitis, ophthalmologists and rheumatologists should work together.

CD4 and CD8 T cell response to the rHSP60 from Klebsiella pneumoniae in peripheral blood mononuclear cells from patients with ankylosing spondylitis / Respuesta de linfocitos T CD4 y CD8 contra la rHSP60 de Klebsiella pneumoniae en células mononucleares de sangre periférica de pacientes con espondilitis anquilosa

Objective. To determine the processing pathways used by peripheral blood mononuclear cells (PBMC) and present the rHSP60Kp, and the T cell subpopulations involved in the response, in patients with ankylosing spondylitis (AS) Methods. The lymphoproliferative response to the rHSP60Kp in PBMC from 14 HLA-B27 + AS patients and 15 B27 healthy controls was assessed by ³H-TdR incorporation. The processing pathways for the rHSP60Kp were analyzed by ³H-TdR incorporation in fresh PBMC from patients using homologous PBMC preincubated with the antigen and specific inhibitors: chloroquine, N-acetyl-L-leucil-L-leucil-L-nor-leucinal (LLnL) or brefeldin A (BFA), fixed with p-formaldehyde (fixed APC). The CD4+/CD8+ T cell subpopulation activated with the antigen was determined by three colours flow cytometry in PBMC from patients. Results. Eight out of fourteen patients showed positive lymphoproliferative responses to the rHSP60Kp while none of the healthy controls responded (p < 0.012). In five patients S.I. was above 4.0. In these patients lymphoproliferation was lower when chloroquine and LLnL was used and it became negative with BFA, indicating that both pathways are used. CD4+ and CD8+ T cells populations expressed CD69 when activated by the rHSP60Kp. Conclusions. Our results suggest that CD4 and CD8 T cells participate in the response to the rHSP60Kp in B27+ AS patients.

Objetivo.Determinar las vías utilizadas por las células mononucleares de sangre periférica (CMSP) de pacientes con espondilitis anquilosante para procesar a la rHSPGO de Klebsiella pneumoniae (rHSPGOKp) y las subpoblaciones de linfocitos T involucrados en la activación. Métodos. Se determinó la respuesta linfoproliferativa, por incorporación de ³H-TdR en CMSP, en presencia de la rHSPGOKp, en 14 pacientes con EA HLA-B27+y en 15 sujetos sanos HLA-B27-. La ruta de procesamiento y presentación de la rHSPGOKp se determinó por incorporación de ³H-TdR en las CMSP de los pacientes utilizando como células presentadoras a las CMSP homologas, preíncubadas con el antígeno y los inhibidores específicos: cloroquína, brefeldína A y N-acetil-L-leucil-L-leucil-L-nor-leucinal (LLnL), y fijadas con p-formaldehído. Se evaluaron las subpoblaciones de linfocitos T CD4+ y CD8+ que expresaron CD69, frente al antígeno, por citometría de flujo. Resultados. Ocho de los 14 pacientes y ninguno de los sujetos sanos, tuvo respuesta linfoproliferativa positiva (IE > 3.0) contra la rHSPGOKp (p < 0.012). En cinco de los pacientes el I.E. fue superior a 4.0. En estos pacientes la linfoproliferación disminuyó cuando se utilizó cloroquína y LLnL, y se hizo negativa cuando se utilizó BFA, lo que indica que ambas vías son empleadas. Las subpoblaciones de linfocitos T (CD4+ y CD8+) expresaron CD69 frente al antigeno. Conclusiones. Nuestros resultados sugieren que ambas poblaciones de linfocitos T: CD4+ y CD8+ participan en la respuesta a la rHSPGOKp.

Comparison of validity of microlymphocytotoxicity and flow cytometry methods with PCR for HLA-B27 antigen typing

The Human Major Histocompatibility Complex [MHC] plays a crucial role in transplantation, transfusion, paternity test and assessment of susceptibility to some diseases associated with HLA-B27. Three of the most fashionable methods for determination of HLA antigens in clinical and research laboratories are microlymphocytotoxicity [MLCT], flowcytometry and polymerase chain reaction [PCR].The purpose of this study was to compare the sensitivity, specificity, and positive and negative predictive values of MLCT and flowcytometry methods with PCR as a gold standard method in determination of HLA-B27 antigen. In the present study, all three above-mentioned techniques have been used for 36 patients suffering from ankylosing spondylitis and 31 healthy volunteers. Specific antisera and monoclonal antibodies against HLA-B27, and allele specific PCR have been used in MLCT, flowcytometry and PCR methods respectively. The results show that sensitivity, specificity, positive and negative predictive values of MLCT method as compared with PCR technique were 83.3%, 100%, 100% and 88.1% respectively. Moreover, sensitivity, specificity, positive and negative predictive values of flowcytometry compared to the PCR technique were 100%, 94.6%, 93.8% and 100% respectively. Based on the results, the flowcytometry method in determination of HLA-B27 is more valid than MLCT in this regard, particularly in research programs. The similarity between the results of our study and those studies done in Europe suggests the probability of resemblance between HLA-B27 subtypes in Europe and in Iran

HLA B27 y las espondilartropatias seronegativas / HLA B27 and seronegative spondyloarthropaties

Se realizo el tipaje serologico para el antigeno HLA B27 a 19 pacientes con espondilartropatias seronegativas para conocer su relacion y, de ellos, 6 resultaron positivos; 94 individuos sanos conformaron el grupo control y en 4 se encontro el antigeno. Los resultados expuestos sugieren la presencia de genes adicionales al B27 en los pacientes con este grupo de enfermedades

Quantificaçäo da interferência do soro na fagocitose de imunocomplexos nas espondiloartropatias soronegativas, lúpus eritematoso sistêmico e doença reumatóide / Quantification of serum interference in the immune complexes phagocytosis in seronegative spondylarthropaties, systemic lupus erythematosus and rheumatoid disease

Cinqüenta e cinco soros de pacientes portadores de espondiloartropatias soronegativas, lúpus eritematoso sistêmico e artrite reumatóide foram selecionados para o estudo. Todos os soros mostravam fator reumatóide negativo pela prova de látex. A determinaçäo da interferência na fagocitose de gamaglobulina agregada por macrófagos de cobaia foi obtida por uma fórmula. A caracterizaçäo dos soros foi discriminada pela reaçäo daqueles que mostraram resultados mais expressivos na interferência sobre a fagocitose, facilitando ou inibindo-a. Os resultados, em valores absolutos e percentuais, mostraram a predominância do fenômeno da interferência na fagocitose, com valores significantes estatisticamente (p<0,05), quando comparado com soro normal. A análise comparativa entre as doenças estudadas na quantificaçäo da interferência do soro na fagocitose de imunocomplexo näo mostrou diferença significativa. A inibiçäo da fagocitose ocorreu com mais predominância no soro de pacientes com síndrome de Reiter e artrite psoriática; no soro de pacientes com síndrome de Reiter houve uma diferença estatisticamente significante na inibiçäo da fagocitose (p=0,0247). A caracterizaçäo da fraçäo sérica responsável pela interferência na fagocitose näo foi demonstrada. No estado atual dos conhecimentos, näo há uniformidade nas curvas de diluiçäo estudadas. É enfatizada a possibilidade de existência de mais de um elemento interferindo na fagocitose de imunocomplexos.

A study of the gram-negative bacterial flora in patients with ankylosing spondylitis

Twenty-eight patients with active definite primary ankylosing spondylitis and fifty-four healthy control subjects were studied. The HLA-B27 antigen was found in 75% of patients and 3.7% of control. Fecal samples from these subjects were cultured for gram-negative enteric bacteria on two occasions within one month. Positive cultures for Klebsiella sp were found in 32.1% of patients and in 22.2% of healthy controls, but this difference was not statistically significant. All obther microorganisms detected were qualitatively and quantitatively similar in both groups. Significantly increased mean values of serum IgA levels were found in the patient group when compared with the control group (P<0.01). The mean serum IgG and IgM levels did not differ statistically between the two groups. There was no correlation between any laboratory or clinical parameter and presence of Klebsiella sp carriage in ankylosing spondylitis patients. These data are consistent with the view that a long time elapses between exposure to a trigger facter and clinical manifestations of the disease