Optimización del algoritmo diagnóstico de anticuerpos antinucleares / Optimization of the diagnostic algorithm of antinuclear antibodies

Introducción: La prueba de anticuerpos antinucleares es una poderosa herramienta en el diagnóstico de las enfermedades reumáticas. Los anticuerpos antinucleares se determinan en el laboratorio por un algoritmo o secuencia que se inicia con prueba de cribado y sigue con la identificación de las especificidades antinucleares más comunes. Pero, ¿cómo interpretar los resultados discordantes entre los dos niveles de estudio de anticuerpos antinucleares? Objetivo: Determinar las especificidades antinucleares menos frecuentes en pacientes positivos de cribado de ANA y negativos de las especificidades más comunes. Métodos: Estudio prospectivo de 88 pacientes consecutivos remitidos para la detección rutinaria de ANA con resultado positivo de cribado por ensayo inmuno-adsorbente ligado a enzima (ELISA) pero negativo de anticuerpos anti-ADN de doble cadena (dc, IgG) y anti-antígenos nucleares extraíbles comunes (ENAc). Las muestras séricas correspondientes fueron evaluadas por inmunofluorescencia indirecta sobre células de carcinoma epidermoide laríngeo humano (IFI-HEp-2) y por ELISA para la detección individual de ANA específicos. Resultados: La prueba de ANA por IFI/HEp-2 resultó positiva en 56/88 (63,6 por ciento) y las especificidades antinucleares se detectaron en 57/88 (64,8 por ciento) muestras, en el orden decreciente de Anti-Nucs: 16/88 (18,2 por ciento); anti-centrómero (CENP-B): 15/88 (17,0 por ciento); -histona: 15/88 (17 por ciento); -PM/Scl: 13/88 (14,8 por ciento); -ADNsc: 11/88 (12,5 por ciento) y -ENAc individuales: 8/88 (9,1 por ciento). La sensibilidad de la IFI-HEp-2 para las especificidades antinucleares fue de 0,83 (IC95 por ciento: 0,72-0,93). De los pacientes negativos de subserología (26/31), 83,9 por ciento no tenían antecedentes de enfermedad reumática asociada a ANA. Conclusiones: La mayoría de los pacientes con resultados discordantes entre el primer y segundo nivel de ANA fueron positivos de especificidades antinucleares menos comunes, pero de reconocido valor diagnóstico(AU)

Introduction: The antinuclear antibody test is a powerful tool for diagnosing rheumatic diseases. Antinuclear antibodies are determined in the laboratory by an algorithm or sequence that starts with a screening test and continues with the identification of the most common antinuclear specificities. But how to interpret the discordant results between the two levels of study of antinuclear antibodies? Objective: To determine the less frequent antinuclear specificities in positive patients of ANA screening and negative of the most common specificities. Methods: A prospective study was done on 88 consecutive patients referred for the routine ANA screening with a positive result of screening by enzyme-linked immunosorbent assay (ELISA) but negative for anti-double-stranded DNA (dc, IgG) and common extractable anti-nuclear antigens (ENAc). The corresponding serum samples were evaluated by indirect immunofluorescence on human laryngeal epidermoid carcinoma cells (IFI-HEp-2) and by ELISA for the individual detection of specific ANA. Results: The ANA test by IFI / HEp-2 was positive in 56/88 (63.6 percent) and the antinuclear specificities were detected in 57/88 (64.8 percent) samples, in decreasing Anti-Nucs order: 16/88 (18.2 percent); anti-centromere (CENP-B): 15/88 (17.0 percent); -histona: 15/88 (17 percent); -PM / Scl: 13/88 (14.8 percent); -ADNsc: 11/88 (12.5 percent) and -ENAc individual: 8/88 (9.1 percent). The sensitivity of IFI-HEp-2 for antinuclear specificities was 0.83 (95 percent CI: 0.72-0.93). No history of rheumatic disease associated with ANA was read in (26/31) 83.9 percent patients with negative subserology. Conclusions: The majority of patients with discordant results between the first and second level of ANA were positive of less common antinuclear specificities, but of recognized diagnostic value(AU)

The clinical research about early diagnosis of small cell lung cancer through mad2 de-tection / 中国肿瘤临床

Objective:To explore combined detection of mad2 with anti-nuclear mitotic spindle apparatus antibody(MSA)and anti-centromere antibody(ACA)and their clinical value for the diagnosis of small cell lung cancer(SCLC).Methods:One hundred and twen-ty SCLC patients,110 non-small cell lung cancer(NSCLC)patients,and 115 pulmonary nodule(PN)patients were enrolled in this study. The expression of mad2 was analyzed by qt-PCR.MSA and ACA were detected by indirect immunofluorescence(IIF)staining.Results:mad2 was overexpressed in SCLC and NSCLC samples(P<0.05).There were significant differences between the results obtained for SCLC and NSCLC samples by qt-PCR(P<0.05).AUC in ROC curve for mad2 expression was 0.799 with an intermediate diagnostic value. In the correlative analysis,the odds ratio of MSA and ACA was 6.94 and 5.60,respectively.In the correlation analysis,Kappa value of mad2 with MSA was 0.49,and Kappa value of mad2 with ACA was 0.42.In the parallel analysis,the sensitivity and specificity was 83.31% and 79.34%,respectively,while the Youden Index was 0.62.Moreover,in the serial analysis,the sensitivity and specificity was 65.32% and 93.35%,respectively,and the Youden Index was 0.59.Conclusions:In comparison with the NSCLC and PN samples,mad2 was overexpressed in SCLC samples.Therefore,mad2 ought to play a critical role in the pathology of SCLC.The combined expression of mad2 with MSA and ACA may contribute to enhancing the sensitivity and specificity of detection;this expression may allow early diag-nosis and clinical diagnosis of SLCC and may be a promising treatment for SCLC.

Autoanticorpos em esclerose sistêmica e sua correlação com as manifestações clínicas da doença em pacientes do Centro-Oeste do Brasil / Autoantibodies in systemic sclerosis and their clinical correlation in patients from a Midwestern region of Brazil

Introdução: a esclerose sistêmica (ES) é uma enfermidade do tecido conjuntivo de caráter autoimune caracterizada pela tríade de injúria vascular, autoimunidade (celular e humoral) e fibrose tecidual. Os autoanticorpos não parecem ser simplesmente epifenômenos, mas sim estarem envolvidos na patogênese da doença. Acredita-se que os autoanticorpos específicos da ES são responsáveis tanto pela amplificação da resposta imune quanto por alvejar os tipos celulares que são relevantes na fisiopatologia da ES. Objetivos: correlacionar o perfil de autoanticorpos específicos (anti-SCL70, ACA, anti-POL3) com as manifestações clínicas e laboratoriais observadas em 46 pacientes com ES da região Centro-Oeste do Brasil. Métodos: pesquisou-se a ocorrência de autoanticorpos específicos em 46 pacientes com diagnóstico de ES e correlacionou-se o tipo de autoanticorpo com as manifestações clínicas e laboratoriais encontradas. Resultados: dentre todos os pacientes avaliados, encontrou-se predomínio feminino (97,8%), idade média de 50,21 anos, cor branca (50%), forma limitada da doença (47,8%), tempo de diagnóstico entre cinco e 10 anos (50%) e tempo de evolução da doença de 9,38 anos. De acordo com o autoanticorpo específico, 24 pacientes apresentavam ACA positivo (52,2%), 15 apresentavam positividade para anti-SCL70 (32,6%) e sete apresentavam anti-POL3 positivo (15,2%). O autoanticorpo anti-SCL70 se correlacionou com a forma difusa da doença, com maior gravidade e atividade da doença, com pior qualidade de vida medida pelo índice HAQ, com maior prevalência de fenômeno de Raynaud objetivo e microcicatrizes de polpas digitais. O ACA se correlacionou com a forma limitada da doença, com o início mais precoce da enfermidade, bem como com maior prevalência de telangiectasias nos pacientes. Já o anti-POL3 se correlacionou com a forma difusa da doença, com maior ocorrência de fenômeno de Raynaud subjetivo e de atrofia muscular. Para as demais variáveis relacionadas ...

Introduction: Systemic sclerosis (SSc) is a connective tissue disease of autoimmune nature characterized by the triad of vascular injury, autoimmunity (cellular and humoral) and tissue fibrosis. Autoantibodies do not seem to be simply epiphenomena, but are involved in disease pathogenesis. It is believed that the SSc-specific autoantibodies are responsible both for amplifying immune response and targeting cell types that are relevant in the pathophysiology of SSc. Objectives: To correlate the profile of the following specific autoantibodies: anti-centromere (ACA), anti-topoisomerase I (topo I) and anti-RNA polymerase III (RNAP III) with clinical and laboratory manifestations were observed in 46 patients with SSc in the Midwest region of Brazil. Methods: The occurrence of specific autoantibodies in 46 patients with SSc was investigated, correlating the type of autoantibody with clinical and laboratory manifestations found. Results: Among all patients evaluated, we found a predominance of females (97.8%), mean age 50.21 years old, Caucasian (50%), limited cutaneous SSc (47.8%), time of diagnosis between 5 and 10 years (50%), and disease duration of 9.38 years. According to the specific autoantibody profile, 24 patients were ACA-positive (52.2%), 15 were positive for anti-topo I (32.6%), and 7 showed positive anti-RNAP III (15.2%). The anti-topo I autoantibody correlated with diffuse scleroderma, with greater disease severity and activity, with worse quality of life measured by the SHAQ index, with a higher prevalence of objective Raynaud's phenomenon and digital pitting scars of fingertips. The ACA correlated with limited scleroderma, with earlier onset of disease, as well as higher prevalence of telangiectasias. The anti-RNAP III correlated with diffuse scleroderma, with a higher occurrence of subjective Raynaud's phenomenon and muscle atrophy. There was no association between the positivity for anti-topo I, ACA and anti-RNAP III antibodies ...

Clinical significance of PM-Scl antibody detection in systemic scleroderma / 国际检验医学杂志

Objective To analyze and discuss the expression of serum polymyositis‐scleroderma(PM‐Scl) antibody and its clinical significance in patients with systemic scleroderma(SSc) .Methods 315 hospitalized patients diagnosed with scleroderma by typical clinical manifestations or skin pathology from 2009 to 2012 were enrolled in the study .All patients were grouped into PM‐Scl antibody positive(PM‐Scl + ) group(90 cases) ,Scl‐70 antibody positive(Scl‐70+ ) group(70 cases) ,anti‐centromere antibody positive( ACA+ ) group(75 cases) and antibody negative group(80 cases) according to autoantibody spectrum .The severity of skin and visceral damage among all the groups were analyzed and compared .Results Patients in PM‐Scl+ group were characterized with different clinical manifestations .Compared with the other 3 groups ,the incidence of myositis in PM‐Scl+ group was significantly higher( all P< 0 .05) ;patients in Scl‐70+ group had higher incidence of visceral organ damage than PM‐Scl+ group(all P < 0 .05) .The incidence of skin lesions ,Raynaud′s phenomenon and capillary expansion in ACA+ group were higher than that of PM‐Scl+ ,while the incidence of interstitial lung disease ,heart disease and kidney disease were lower(all P< 0 .05) .Conclusion It is helpful for clinicists′ further understanding of common autoantibodies in Ssc patients and making correct assessment of the disease through analyzing the expression of PM‐Scl antibody .

The detection of scleroderma-related autoantibodies and its clinical significance in 135 Chinese patients with systemic sclerosis / 中华微生物学和免疫学杂志

Objective To detect the expression of scleroderma-related autoantibodies, such as anti-Scl-70, anli-centromere antibody ( ACA)and anti-RNA polymerase Ⅲ ( ARA) , and their relationship with clinical features in Chinese systemic sclerosis (SSc) patients. Methods One hundred and thirty-five Chinese SSc patients from the clinical database of the Scleroderma Trials and Research Group proposed by European League Against Rheumatism's Scheroderma Trial and Research Group( EUSTAR) were consecutively enrolled. The expression of ARA, anti-Scl-70 and ACA were detected through linear immunoblotting, double immunodiffusion and indirect irnmunofluorescence, respectively. The relevance between the existing of autoantibodies and clinical manifestations was analyzed statistically. Results Among the 135 Chinese SSc patients, the prevalence of anti-Scl-70, ACA, ARA were 49. 6% , 13.3 % and 8.9% respectively. Patients with anti-Scl-70 antibody had significantly shorter disease course [(71 ±59) month vs (90 ± 103) month, P = 0.041] , higher proportion of interstitial lung disease ( P = 0. 031) but lower of pulmonary arterial hypertension (P =0.042). Modified Rodnan's skin score (P=0.008) and prevalence of facial and cervical cutaneous sclerosis (P = 0. 002) , distal (to elbow/knee ) cutaneous sclerosis ( P = 0. 004 ) and digital pitting scarring/disappear of digital pad were all significantly higher in anti-Scl-70 positive group. Patients with AC A had longer disease course ( P = 0. 036) , lower IgM level ( P = 0. 045) and were less prevalent of interstitial lung disease ( P =0. 045). Patients with ARA had higher serum creatinine and urea nitrogen level ( P ＜ 0.001) although otherwise features had unremarkable differences. Conclusion Scleroderma-related autoantibodies have relevance with different clinical manifestation and detection of these autoantibodies may be helpful to the diagnosis of SSc, organ involvement evaluation and predicting outcomes. The clinical relevances of autoantibodies in Chinese SSc patients may differ from other areas or races.

Plasma paraoxonase activity in patients with systemic sclerosis.

Background & objectives: Systemic sclerosis (SSc) is a connective tissue disease characterized vascular damage and fi brosis. The aim of this study was to investigate the possible relation between systemic sclerosis and paraoxonase which is an antioxidant enzyme on the HDL. Methods: Twenty nine patients with SSc and 16 healthy subjects (control group) participated in the study. Plasma cholesterol levels, anti-centromere antibody (ACA) levels and paraoxonase (PON) activities were measured. Results: Lower level of high-density lipoprotein (HDL) cholesterol was observed in ACA negative SSc patients than in controls. Paraoxonase activity in ACA positive patients was however found to increase relative to control and ACA negative patient groups. Interpretation & conclusions: Our fi ndings suggested that low HDL level in ACA negative SSc patients might be one of the factors leading to some vascular problems, and increased PON activity in ACA positive SSc group might have some role in the limitation of cutaneous sclerotic process observed in these patients. However, these preliminary fi ndings need to be confi rmed with a larger sample.

Clinical Significance of Anti-centromere Antibody in Rheumatoid Arthritis / 대한류마티스학회지

OBJECTIVE: Anti-centromere antibody (ACA) is known to be specific for CREST syndrome, but individual studies showed variations in its distribution among related diseases. According to the authors'study on 56 ACA positive patients, 37 patients were known to have rheumatoid arthritis (RA). As a consequence, the authors studied the clinical significance of ACA positive RA patients. MEHTODS: Specific clinical findings, radiologic studies, and laboratory data were investigated on 72 ACA positive and on 50 ACA negative RA patients. ACA tests were performed by indirect immunoflourescence assay with IT-1 cell line using IT-AIT kit (ImmunoThink(r), Korea) RESULTS: No specific differences were noted between the ACA positive and the negative group of RA. However, there were a few notable findings between the low titer and the high titer group of ACA positive RA. In comparison with the low titer group, the high titer group showed lesser disease activity, more cases of seronegative RA (39.2%4.8%) and thyroid diseases (11.8%>0%). They generally showed atypical RA patterns and the antibodies tend to remain at high titer state. CONCLUSION: Since the high titer ACA group of RA patients showed specific clinical findings, it is thought to be necessary to classify such group into a new subset of RA. And such classification would be helpful in diagnosing some atypical forms of RA patients. More studies on these new types of patients as well as their prognoses should be investigated in the future.