RESUMO
BACKGROUND: The relationship between the risk of celiac disease and both the age at which gluten is introduced to a child's diet and a child's early dietary pattern is unclear. METHODS: We randomly assigned 832 newborns who had a first-degree relative with celiac disease to the introduction of dietary gluten at 6 months (group A) or 12 months (group B). The HLA genotype was determined at 15 months of age, and serologic screening for celiac disease was evaluated at 15, 24, and 36 months and at 5, 8, and 10 years. Patients with positive serologic findings underwent intestinal biopsies. The primary outcome was the prevalence of celiac disease autoimmunity and of overt celiac disease among the children at 5 years of age. RESULTS: Of the 707 participants who remained in the trial at 36 months, 553 had a standard-risk or high-risk HLA genotype and completed the study. At 2 years of age, significantly higher proportions of children in group A than in group B had celiac disease autoimmunity (16% vs. 7%, P=0.002) and overt celiac disease (12% vs. 5%, P=0.01). At 5 years of age, the between-group differences were no longer significant for autoimmunity (21% in group A and 20% in group B, P=0.59) or overt disease (16% and 16%, P=0.78 by the log-rank test). At 10 years, the risk of celiac disease autoimmunity was far higher among children with high-risk HLA than among those with standard-risk HLA (38% vs. 19%, P=0.001), as was the risk of overt celiac disease (26% vs. 16%, P=0.05). Other variables, including breast-feeding, were not associated with the development of celiac disease. CONCLUSIONS: Neither the delayed introduction of gluten nor breast-feeding modified the risk of celiac disease among at-risk infants, although the later introduction of gluten was associated with a delayed onset of disease. A high-risk HLA genotype was an important predictor of disease. (Funded by the Fondazione Celiachia of the Italian Society for Celiac Disease; CELIPREV ClinicalTrials.gov number, NCT00639444.).
Assuntos
Doença Celíaca/prevenção & controle , Dieta , Proteínas Alimentares/administração & dosagem , Glutens , Antígenos HLA/genética , Fatores Etários , Idade de Início , Autoanticorpos/sangue , Aleitamento Materno , Doença Celíaca/diagnóstico , Doença Celíaca/genética , Criança , Pré-Escolar , Feminino , Proteínas de Ligação ao GTP/imunologia , Genótipo , Gliadina/imunologia , Glutens/administração & dosagem , Humanos , Lactente , Recém-Nascido , Intestino Delgado/patologia , Estimativa de Kaplan-Meier , Masculino , Estudos Prospectivos , Proteína 2 Glutamina gama-Glutamiltransferase , Risco , Transglutaminases/imunologiaRESUMO
OBJECTIVE: To investigate the polymorphisms in the promoter region of the B lymphocyte stimulator (BLyS) gene as markers of response to rituximab (RTX) in rheumatoid arthritis (RA). METHODS: The study was first conducted in 152 Italian RA patients and then replicated in an additional 117 RA patients (73 Italian, 44 British). The European League Against Rheumatism response criteria were used to evaluate the response rate at months 4 and 6 after the first cycle of RTX, by means of the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate; patients were classified according to the best response shown between months 4 and 6. BLyS promoter polymorphisms were analyzed by polymerase chain reaction followed by the analysis of the restriction fragments, BLyS promoter haplotypes were analyzed using the expectation-maximization algorithm, and BLyS serum levels were analyzed using enzyme-linked immunosorbent assay. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs). RESULTS: The TTTT BLyS promoter haplotype appeared to be significantly associated with response to RTX only in the subset of seropositive patients (those positive for rheumatoid factor and/or anti-cyclic citrullinated peptide). The replication study confirmed that this association was limited to seropositive RA patients in whom treatment with anti-tumor necrosis factor (anti-TNF) agents had previously failed. In the whole series of seropositive patients in whom anti-TNF agents had previously failed, patients carrying the TTTT BLyS promoter haplotype were more prevalent in good responders (18 of 43 [41.9%]) than in moderate responders (20 of 83 [24.1%]) or in nonresponders (1 of 21 [4.8%]) (for good responders versus nonresponders, OR 14.4 [95% CI 1.77-117.39], P=0.0028). Furthermore, multivariate analysis selected the TTTT BLyS promoter haplotype as an independent marker of good response to RTX (for good responders versus nonresponders, OR 16.2 [95% CI 1.7-152.5], P=0.01; for good responders versus moderate responders and nonresponders combined, OR 3.1 [95% CI 1.2-7.8], P=0.02). The relationship between BLyS polymorphisms and BLyS serum levels remained unclear. CONCLUSION: BLyS promoter genotyping may be suitable for identifying seropositive RA patients who may have a good response to RTX after anti-TNF agents have failed.
Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Fator Ativador de Células B/genética , Fator de Necrose Tumoral alfa/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/genética , Sedimentação Sanguínea , Estudos de Coortes , Resistência a Medicamentos/genética , Inglaterra , Ensaio de Imunoadsorção Enzimática , Feminino , Haplótipos , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Regiões Promotoras Genéticas/genética , Estudos Retrospectivos , Rituximab , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: A lyophilised reference serum from one patient with rheumatoid arthritis (RA) diluted with serum samples from healthy subjects was evaluated as a possible first international standard for anticitrullinated peptide antibodies (ACPAs). METHODS: The authors used 12 commercial ELISAs for ACPA detection in the reference serum and for testing the linearity of the assays by studying twofold serial dilutions. To test the effectiveness of the standardisation, sera from 20 RA patients with variable antibody concentrations were analysed, and the relative concentrations were calculated using both the kit's own curve and the six dilutions of the reference serum as a calibration curve. Fifty sera from normal healthy subjects were used to calculate cut-off values for the reference serum using each commercial kit. RESULTS: The calibration curve obtained for each of the 12 methods using the reference sample dilutions as calibrator allowed harmonisation of the ACPA concentration of the 20 RA serum samples, significantly reducing the dispersion of the values. The mean coefficient of variation (CV) was reduced from 76.4% to 27.9% (p=0.018) and from 85.9% to 33.5% (p=0.028) for the medium/high and negative samples, respectively. Low positive sera CV was also reduced, but to a smaller degree, from 82.5% to 55.5% (p=0.043). CONCLUSION: This first evaluation of the behaviour of the ACPA reference serum demonstrated that it tested positive in all the assays and that it may be used as a reference standard for establishing calibration curves, reducing the dispersion of antibody values and better comparing results obtained from different methods/laboratories.
Assuntos
Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Peptídeos Cíclicos/imunologia , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Biomarcadores/sangue , Calibragem , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Peptídeos Cíclicos/sangue , Kit de Reagentes para Diagnóstico , Padrões de ReferênciaRESUMO
OBJECTIVE: To evaluate the frequency and the natural history of potential (serology positive/Marsh 0-1 histology) celiac disease (CD) in children with a family risk of CD and factors associated with potential instead of overt (serology positive/Marsh 2-3 histology) CD expression. STUDY DESIGN: Two-year follow-up study of 96 children (57 females; mean age: 29 ± 12 months) prospectively investigated from birth with: (1) a CD-affected first-degree relative; (2) positivity of serum IgA anti-tissue transglutaminase (tTG) or IgG antigliadin and IgA deficiency; and (3) the results of small intestinal biopsy. Children with potential CD were advised to remain on a gluten containing diet, repeat the celiac antibodies every 6 months, and to have an intestinal biopsy performed in case of persistently high anti-tTG level. Factors discriminating between potential and overt CD were analyzed by decision tree analysis based on the C4.5 algorithm. RESULTS: Twenty-four children had potential and 72 overt CD. The stronger predictors of potential CD were lack of symptoms, anti-tTG level lower than 11-fold the upper normal limit, age lower than 24 months, and breastfeeding longer than 8 months. Eighteen out of 21 (86%) patients with potential CD continuing a gluten-containing diet became antibody negative, 1/21 (5%) developed overt CD, and 2/21 (9%) had fluctuating antibodies levels after 2 years. CONCLUSIONS: The prevalence of potential CD and the percentage of short-term loss of CD-related-antibodies are high in infants at-family-risk for CD. In symptomless children with a positive celiac serology, the decision of performing an intestinal biopsy should be preceded by a period of repeated serological testing.
Assuntos
Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Algoritmos , Biópsia , Pré-Escolar , Saúde da Família , Feminino , Glutens/metabolismo , Antígenos HLA/metabolismo , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Masculino , Pediatria/métodos , Fenótipo , Prevalência , Estudos Prospectivos , Risco , Transglutaminases/sangueRESUMO
AIM: To assess the predictive value for chronic autoimmune gastritis (AIG) of the combined assay of anti-parietal-cell antibodies (PCA), anti-intrinsic-factor antibodies (IFA), anti-Helicobacter pylori (Hp) antibodies, and measurement of blood gastrin. METHODS: We studied 181 consecutive patients with anemia, due to iron deficiency resistant to oral replacement therapy or to vitamin B12 deficiency. RESULTS: 83 patients (45.8%) tested positive for PCA and underwent gastroscopy with multiple gastric biopsies. On the basis of the histological diagnosis, PCA-positive patients were divided into 4 groups: (1) 30 patients with chronic atrophic gastritis; they had high concentrations of PCA and gastrin and no detectable IFA; (2) 14 subjects with metaplastic gastric atrophy; they had high PCA, IFA, and gastrin; (3) 18 patients with nonspecific lymphocytic inflammation with increased PCA, normal gastrin levels, and absence of IFA; (4) 21 patients with multifocal atrophic gastritis with "borderline" PCA, normal gastrin, absence of IFA and presence of anti-Hp in 100% of the cases. CONCLUSIONS: The assay of four serological markers proved particularly effective in the diagnostic classification of gastritis and highly correlated with the histological profile. As such, this laboratory diagnostic profile may be considered an authentic "serological biopsy."
Assuntos
Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Biópsia/métodos , Gastrite Atrófica/diagnóstico , Testes Sorológicos/métodos , Idoso , Anticorpos/imunologia , Doenças Autoimunes/microbiologia , Doenças Autoimunes/patologia , Feminino , Gastrinas/imunologia , Gastrite Atrófica/imunologia , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Gastroscopia/métodos , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/patologia , Helicobacter pylori/imunologia , Humanos , Fator Intrínseco/imunologia , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Células Parietais Gástricas/imunologia , Células Parietais Gástricas/patologiaRESUMO
OBJECTIVES: Positivity of both immunoglobulin A anti-tissue transglutaminase (TTG) and anti-endomysium antibodies (EMA) has a positive predictive value of nearly 100% for celiac disease (CD). The objective of the present study was to evaluate whether patients of any age, with high pretest probability of CD and high titre of anti-TTG and EMA positivity, have a high probability of intestinal damage and may not require the biopsy for final diagnosis. METHODS: A retrospective analysis of 412 consecutively referred patients, age range 10 months to 72 years, who underwent small-bowel biopsy for suspicion of CD and positivity to both anti-TTG and EMA, was performed at 4 Italian centers. Biopsies were evaluated independently by 2 pathologists using Marsh modified classification; in cases of dissimilar results, a third pathologist examined the biopsy. The final histological finding diagnosis was expressed as the prevalent or highest score assigned by the pathologist board. RESULTS: Three hundred ninety-six patients (96.1%) had histological findings consistent with CD (grade 2 and 3a, 3b, or 3c of modified Marsh classification). An anti-TTG ratio ≥ 7 was able to identify with the 3 assays used (Celikey, anti-TTG immunoglobulin A, EuTTG) all of the patients with significant mucosal damage (Marsh ≥ 2) independent of age and sex; specificity and positive predictive value were 100%. An anti-TTG ratio >20 was more specific (99.8%) for identification of patients with villous atrophy (Marsh 3 a, b, or c). CONCLUSIONS: Patients with positivity of anti-TTG ≥ 7-fold cutoff, confirmed by positivity to EMA, have a high-degree probability of duodenal damage. In selected conditions, a duodenal biopsy may be avoided and a confirmed greatly positive anti-TTG result could be the basis to prescribe a gluten-free diet.
Assuntos
Doença Celíaca/imunologia , Doença Celíaca/patologia , Duodeno/patologia , Proteínas de Ligação ao GTP/imunologia , Imunoglobulina A/sangue , Músculos/imunologia , Transglutaminases/imunologia , Adolescente , Adulto , Idoso , Biópsia , Doença Celíaca/classificação , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Proteína 2 Glutamina gama-Glutamiltransferase , Estudos Retrospectivos , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Adulto JovemRESUMO
BACKGROUND: In the diagnosis of celiac disease (CD), serum assays for anti-endomysium (EMA) and anti-transglutaminase (anti-tTG) antibodies have excellent diagnostic accuracy. However, these assays are less sensitive in young pediatric patients. Recently, a new ELISA test using deamidated gliadin peptides (DGP) as antigen has proved to be very sensitive and specific even in pediatric patients. In addition, anti-actin IgA antibodies (AAA) is another test that can be used in CD patients because antibody concentrations correlate with the degree of villous atrophy. This study evaluated the clinical accuracy of anti-tTG, EMA, AGA, anti-DGP and AAA and the effectiveness of these in different combinations for diagnosing CD in a large cohort of pediatric patients. METHODS: Sera of 150 children under 6 years of age were tested: 95 patients had a diagnosis of CD, while 55 patients who did not suffer from CD were used as controls. Anti-DGP IgA/IgG and AAA were assayed with ELISA kits, while anti-tTG IgA/IgG and AGA IgG/IgA were assayed using a quantitative fluoroimmunoassay. The EMA test was conducted by indirect immunofluorescence. RESULTS: Seventy-six of 95 (80%) CD patients were positive for DGP IgA and/or tTG IgA. Eighty of 95 (84.2%) patients were positive for DGP IgG and/or tTG IgA. None of the controls were positive for these antibodies. Eighty-four of 95 (88.4%) patients and 8/55 (14.5%) controls were positive for AAA and/or anti-tTG IgA. CONCLUSIONS: In very young children, association of anti-tTG IgA with anti-DGP IgG is the best test combination for diagnosing CD, yielding a cumulative sensitivity of 84.2% and a specificity of 100%.
Assuntos
Doença Celíaca/diagnóstico , Técnicas de Laboratório Clínico/normas , Estudos de Casos e Controles , Doença Celíaca/sangue , Pré-Escolar , Técnicas de Laboratório Clínico/economia , Ensaio de Imunoadsorção Enzimática , Feminino , Imunofluorescência , Humanos , Lactente , Masculino , Padrões de Referência , Sensibilidade e EspecificidadeRESUMO
UNLABELLED: Diabetes mellitus is a common autoimmune endocrine disorder associated with organ-specific autoantibodies which are frequently detected at the time of diagnosis. Some of these antibodies are specific to the pancreas (GAD, IA2, ICA) while others are related to different autoimmune diseases. AIM OF THE STUDY: To define the prevalence of thyroid autoimmune disease in Libyan patients with type 1 diabetes mellitus (T1DM) since no similar studies have been performed in Libya. MATERIALS AND METHODS: Blood samples were collected from 218 patients with T1DM who are followed by the Pediatric Department, Tripoli Medical Center, Libya. All sera were analyzed in Italy (Laboratory of Immunopathology and Allergy, Udine). The patients were composed of 123 females (56.4%) and 95 males (43.6%), mean age 12.2 ± 4.6 years (range 2.1-24.5 years), mean duration of diabetes 4.7 ± 4.0 years (range 0.1-17.5 years). Sera were tested for anti-thyroperoxidase (TPO) and anti-thyroglobulin antibodies (TG). TSH and FT4 concentrations were measured in all subjects. GAD, IA-2 was also measured. RESULTS: Of the diabetic children, 23.4% were positive for anti-microsomal peroxidase antibodies (TPO-Ab) and 7.8% for antithyroglobulin antibodies (TG-Ab); whereas 6.9% of the patients were positive for both TPO-Ab and TG-Ab. Of the T1DM patients who were positive for TPO-Ab, 66.6% were females. The majority (57%) of the patients who were positive for TPO had diabetes for longer than 5 years. Five patients (2.3%) had evidence of subclinical hypothyroidism whereas two patients (0.9%) had overt hypothyroidism. Two patients had subclinical hyperthyroidism and two (0.9%) had overt hyperthyroidism. Interestingly, 16.2% of patients were positive for both thyroid and pancreatic antibodies. CONCLUSIONS: The prevalence of autoimmune thyroid disease in type 1 diabetic patients is higher than in the general population. A routine screening strategy should be implemented with the determination of anti-thyroid antibodies and TSH in type 1 diabetic patients, particularly in girls, and in patients with diabetes of more than 5 years duration. Patients who have positive TPO antibodies may need the assessment of thyroid function at shorter intervals.
Assuntos
Complicações do Diabetes/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Tireoidite Autoimune/epidemiologia , Adolescente , Anticorpos/sangue , Criança , Pré-Escolar , Estudos de Coortes , Complicações do Diabetes/diagnóstico , Feminino , Humanos , Líbia/epidemiologia , Masculino , Pâncreas/imunologia , Prevalência , Tireoidite Autoimune/sangue , Tireoidite Autoimune/diagnóstico , Adulto JovemRESUMO
BACKGROUND: Assays for IgG antibodies against deamidated gliadin (IgG-anti-dGli) are comparable in performance with tests detecting IgA antibodies against tissue transglutaminase (IgA-anti-tTG) in diagnosing celiac disease (CD). IgA-anti-tTG are absent in IgA deficiency, a condition often associated with CD. In IgA deficiency, IgG-anti-tTG, which have a lower overall diagnostic accuracy, are routinely measured. We examined whether IgG-anti-dGli would be useful for diagnosing CD in patients with IgA deficiency. METHODS: We studied 34 IgA-deficient CD patients, 185 IgA-competent newly diagnosed children with CD, 316 children without CD, 400 adult blood donors, and 6 control IgA-deficient individuals without CD. Anti-dGli and anti-tTG were measured by ELISA, and endomysium antibodies (EmA) were measured by immunofluorescence on monkey esophagus (IgA as well as IgG class for all antibodies). We calculated diagnostic sensitivity (percentage of patients above cutoff with 95% CIs) according to age-specific cutoffs for 95% diagnostic specificity and according to cutoffs proposed by the manufacturer of the assays. RESULTS: No IgA-deficient CD patients were positive for any IgA-based antibody assay. Diagnostic sensitivity of IgG-anti-tTG was 91.2% (95% CI 76.3%-97.7%) according to age-specific cutoffs and 82.4% (66.1%-92.0%) according to manufacturer cutoffs. The diagnostic sensitivity of IgG-EmA was 75.8% (58.8%-87.4%) and the sensitivity of IgG-anti-dGli was 88.2% (72.8%-95.9%) according to both cutoffs. CONCLUSIONS: IgG-anti-dGli and IgG-anti-tTG have comparable diagnostic sensitivities for IgA-deficient celiac patients. IgG-anti-dGli may be useful for diagnosing CD in IgA-deficient patients.
Assuntos
Doença Celíaca/diagnóstico , Gliadina/imunologia , Deficiência de IgA/complicações , Imunoglobulina G/imunologia , Adolescente , Adulto , Idoso , Doença Celíaca/complicações , Doença Celíaca/imunologia , Criança , Pré-Escolar , Feminino , Gliadina/sangue , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Peptídeos/sangue , Peptídeos/imunologia , Sensibilidade e EspecificidadeRESUMO
BACKGROUND AND AIM: We evaluated the diagnostic performance of an ELISA test for anti-gliadin IgA and IgG antibodies, which uses synthetic deamidated gliadin peptides (anti-gliadin antibodies, AGAs) as coating; the results were compared with a test that uses extracted gliadin (AGAe). METHODS: The study was conducted on the sera of 144 patients suffering from celiac disease (CD), including 20 patients with IgA deficiency and 9 who were following a gluten-free diet (GFD), and 129 controls. RESULTS: In the 115 CD patients (without IgA deficiency), the sensitivity of AGAe IgA and IgG was 32.2 and 60.9%, whereas that of AGAs IgA and IgG was 59.1 and 72.2%. The specificity for AGAe IgA and IgG, and AGAs IgA and IgG was 93.8 and 89.9%, and 96.9% and 99.2%, respectively. Of the 20 patients with CD and IgA deficiency, 7 tested positive for AGAe IgG and 14 for AGAs IgG. The test using deamidated gliadin peptides performed better in terms of sensitivity and specificity than the AGA tests with extracted antigen. CONCLUSIONS: The very high specificity of the AGAs IgG test (99.2%) also suggests that patients who test positive with this assay require a thorough followup, even if the anti-tissue transglutaminase antibodies (anti-tTG) and anti-endomysial autoantibodies (EMA) assays are negative.
Assuntos
Anticorpos/sangue , Anticorpos/imunologia , Doença Celíaca/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Gliadina/imunologia , Adolescente , Adulto , Idoso , Autoanticorpos/sangue , Autoanticorpos/imunologia , Estudos de Casos e Controles , Doença Celíaca/sangue , Doença Celíaca/imunologia , Criança , Pré-Escolar , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Peptídeos/imunologia , Curva ROC , Sensibilidade e Especificidade , Testes Sorológicos , Transglutaminases/imunologia , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: BLyS (B-Lymphocyte stimulator) is over-expressed in several tumoral settings, with direct or indirect effects on neoplastic proliferation and possibly representing a therapeutic target. In this study, we explored the role of BLyS in a large population of patients with neuroendocrine tumors (NETs). METHODS: The study analyzed the stored sera of 124 consecutive unselected patients with NETs: 36 lung carcinoids (24 typical, 12 atypical), 47 gastroenteric tract and 41 pancreatic (30 non-functioning and 11 functioning: 9 insulinomas, 2 glucagonomas). In 23 cases, BLyS was repeatedly assessed during the follow-up and the disease was monitored (progression, stabilization or remission) according to the RECIST criteria. Patients were compared to 92 age and sex-matched blood donors (BDs). Serum levels of BLyS and Chromogranin A (CgA) were analyzed by ELISA. RESULTS: NET patients showed significantly higher BLyS levels than BDs (1274±809 pg/ml vs. 587±173 pg/ml; p<0.0001). BLyS correlated weakly with CgA (r=0.19 and p=0.035) but did not correlate with Ki67, grading, metastasis, histological type and site. In patients with sustained remission after surgery, BLyS and CgA both showed a gradual reduction over time. Patients with progressing disease showed higher BLyS levels compared to stable patients (1524±694 pg/ml vs. 1168± 373 pg/ml; p= 0.033). BLyS serum levels remained stable in remission and therapy-controlled patients, while increased in the follow-up of progressing cases. CONCLUSION: Higher BLyS levels identify patients with a more severe disease, characterized by progression despite treatments, possibly representing a factor implicated in the proliferation of the neoplastic cells or in sustaining the neoplastic environment.
Assuntos
Fator Ativador de Células B/sangue , Biomarcadores Tumorais/sangue , Tumores Neuroendócrinos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima , Adulto JovemRESUMO
Immunology laboratories perform diagnostic tests to identify the autoantibody markers needed to classify disorders which are complex, often rare, and hard to define. The recent introduction of new markers and the use of increasingly complicated assay procedures can cause difficulty in interpreting test results. Moreover, during the performance of some tests, some autoantibodies which were not requested, and consequently not expected, may be identified by chance. It is advisable for these positive results to be reported only when they have a high predictive value and suggest the possible presence of an autoimmune disease. An interpretative comment on autoantibody test results is crucial in a number of cases: when autoantibodies with a significant clinical correlation (high specificity) are found; when two or more methods are used to determine the same autoantibody and the results disagree; when unexpected autoantibody positivity is found and in case of results generated by further diagnostic tests conducted by the laboratory on its own initiative. The interpretative comment should be based on the patient's personal characteristics (sex, age) and the other laboratory parameters available; it should specify the diagnostic accuracy of the assay methods used, the clinical and diagnostic correlations of the antibodies which tested positive, and any further tests needed to complete the diagnostic process.
Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/diagnóstico , Testes Imunológicos , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Erros de Diagnóstico , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como AssuntoRESUMO
Array technology and proteomics are about to launch the era of multiplexed analysis, which allows simultaneous detection of numerous autoantibody specificities and the possibility of defining broad autoantibody profiles. This will probably improve disease staging, risk stratification, prognosis and treatment. However, although these technologies are very promising, they are still in their infancy, and therefore need to undergo strict analytical and clinical validation processes. The latter should involve clinicians and pathologists in prospective, multicentric studies conducted on large numbers of patients to define the specific significance of the various autoantibody profiles. Establishing common standards for the publication and sharing of microarray-generated data will be important for this purpose. Only when these studies have been completed will these new technologies find a place in clinical laboratories. Although we are entering a decade which will probably see a radical change in the diagnostic approach to autoimmune diseases, we do not yet have sufficient knowledge to apply proteomic technologies on a large scale. For the time being, therefore, it is advisable to continue using well-established approaches and diagnostic algorithms such as those reported in the international guidelines, which have been prepared in accordance with the principles of appropriateness and evidence-based medicine.
Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/diagnóstico , Análise Serial de Proteínas , Proteômica , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Reações Falso-Positivas , Humanos , Guias de Prática Clínica como Assunto , Análise Serial de Proteínas/métodos , Análise Serial de Proteínas/normas , Proteômica/métodos , Proteômica/normas , Sensibilidade e EspecificidadeRESUMO
Anti-prothrombin (anti-PT) antibodies are recently identified antibodies directed toward a phospholipid-binding protein (prothrombin), which deserve attention for the reported clinical and pathogenic relevance in antiphospholipid syndrome and systemic lupus erythematosus (SLE). We have recently carried out a longitudinal study on the predictive value of anti-PT antibodies in SLE showing that they have a higher diagnostic accuracy for thrombosis than anti-beta(2)-GPI and anticardiolipin antibodies, and, along with LAC activity, are the best predictors of thromboembolic events in SLE patients.
Assuntos
Anticorpos/sangue , Anticorpos/imunologia , Protrombina/imunologia , Ensaio de Imunoadsorção Enzimática , HumanosRESUMO
Autoantibodies against DFS70 (dense fine speckles 70) antigen have recently been identified among antinuclear antibodies (ANA) in patients with various inflammatory diseases and in patients with different types of cancer. These antibodies are recognized using indirect immunofluorescence (IIF) on HEp-2 cells, by a fine speckled nuclear staining in interphase HEp-2 cells and a positive reaction in the chromosome region of mitotic cells. Given that the DFS70 protein is also known as the lens epithelium-derived growth factor, this study was performed with two objectives: (a) to assess the prevalence of these antibodies in patients sent for ANA testing and in 334 patients with different types of neoplasia and (b) to determine whether the lens tissue was a suitable substrate for the detection of antibodies specific to lens proteins. During routine workup for ANA detection by the IIF method, we found 172 DFS70-positive sera among 21,516 consecutive samples (prevalence, 0.8%). In the group of patients with neoplastic disease, 6 of 334 (1.8%) were anti-DFS70-positive. DFS70-positive sera were then assayed by the IIF method on cryostatic sections of mouse eye at a dilution of 1:40 with an anti-human IgG conjugate. Among the 172 DFS70-positive samples detected by the ANA screening, 32 (19%) were strongly reactive against the reticular fibers of the lens; 8 (5%) were positive only to the corneal epithelium (nuclear negative); 5 (3%) were positive both for the cornea and the lens fibers; 13 (7%) stained only the nuclei of lens and cornea cells, and 4 (2%) were positive against the ciliary muscle. Among the patients with neoplastic diseases, only one with lung cancer reacted weakly with the reticular fibers of the lens. Sera from 20 healthy blood donors were negative. In this preliminary study, we have shown that the prevalence of anti-DFS70 antibodies is much lower than previously reported, both in patients screened for ANA and in patients with cancer. We have also seen that some DFS70-positive sera have antibodies that recognize antigens of the lens. Further studies are needed to investigate the fine specificity and the possible significance of these new autoantibodies.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/imunologia , Autoanticorpos/imunologia , Córnea/imunologia , Cristalino/imunologia , Fatores de Transcrição/imunologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Criança , Pré-Escolar , Córnea/metabolismo , Feminino , Humanos , Cristalino/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: To evaluate the diagnostic characteristics of commercially available IgG anti-tTG assays in selective IgA deficiency (SIgAD), we tested different IgG anti-tTG methods and compared the results with those obtained from two other tests: one for IgG anti-gliadin (AGA) and one for IgG to deaminated gliadin peptides (DGP). METHODS: 20 CD patients with SIgAD and 113 controls (9 patients with SIgAD without CD; 54 patients with chronic liver disease; 50 healthy subjects) were tested with 9 IgG anti-tTG assays (2 of which are enriched with gliadin peptides), one IgG AGA assay and one IgG anti-DGP assay. RESULTS: Using optimal cutoffs as determined by ROC curves, the sensitivity of IgG anti-tTG methods ranged from 75% (1 kit) to 95% (7 kits) and the specificity from 94% (1 kit) to 100% (5 kits). Sensitivity and specificity were 40% and 87% for IgG AGA, and 80% and 98% for IgG anti-DGP, respectively. CONCLUSIONS: All IgG anti-tTG methods evaluated are reliable serologic assays for the diagnosis of CD in patients with SIgAD and perform better than the gliadin-based assays used in this study. The tests containing both tTG and gliadinic peptides are burdened by a lower specificity than the anti-tTG assays.
Assuntos
Autoanticorpos/sangue , Doença Celíaca , Gliadina/imunologia , Imunoglobulina G/sangue , Kit de Reagentes para Diagnóstico , Transglutaminases/imunologia , Adolescente , Adulto , Doença Celíaca/diagnóstico , Doença Celíaca/imunologia , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Deficiência de IgA/sangue , Deficiência de IgA/imunologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: The onset of coeliac disease (CD) in the first year of life is uncommon and the diagnosis can be challenging due to the suboptimal sensitivity of tissue transglutaminase antibodies (tTG) at this age and the many other possible causes of malabsorption in infants. Antibodies to deamidated gliadin peptides (anti-DGPs), especially IgG, may appear earlier than IgA anti-tTG in very young children with CD. CASE PRESENTATION: We report here on an 8-month-old child who was evaluated for failure to thrive, constipation and developmental delay. The symptoms started following gluten introduction in the diet. Laboratory tests showed high fecal elastase concentration, normal serum IgA levels with positive IgG and IgA anti-DGPs, whereas anti-tTG were not detected. The duodenal biopsy revealed a complete villous atrophy (Marsh-Oberhuber 3C). The culture of biopsy fragments in the presence of gliadin peptides did not stimulate the production of IgA anti-endomysial antibodies. Genetic testing proved the child was positive for HLA-DQ2 (DQA1*05; DQB1*02) and HLA-DQ8 (DQA1*03, DQB1*0302). Having initiated the gluten-free diet, the symptoms disappeared and the infant experienced rapid catch-up growth with normalization of psychomotor development. CONCLUSIONS: This case report highlights the utility of anti-DGPs for screening infants with suspected CD. The pattern with positivity for IgG and IgA anti-DGPs only is rare in IgA-competent children with biopsy-proven CD. It could be explained in infancy as immaturity of the adaptive immune system.
Assuntos
Doença Celíaca/diagnóstico , Dieta Livre de Glúten/métodos , Gliadina/imunologia , Gliadina/metabolismo , Autoanticorpos/imunologia , Doença Celíaca/dietoterapia , Doença Celíaca/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Seguimentos , Humanos , Lactente , Masculino , Medição de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
PURPOSE: To explore the role of plasmatic platelet-activating factor acetylhydrolase (PAF-AH), a marker of cardiovascular risk, in patients with anti-phospholipid antibodies (aPL). METHODS: PAF-AH activity was assessed in a series of 167 unselected patients screened for aPL in a context of thrombotic events, risk of thrombosis or obstetric complications and in 77 blood donors. RESULTS: 116/167 patients showed positive results for at least one aPL among IgG/IgM anti-prothrombin/phosphatidylserine (aPS/PT), anti-cardiolipin (aCL), anti-beta2-glycoprotein I (aß2GPI) or lupus anticoagulant (LAC), while 51/167 patients resulted aPL-negative. LAC+ patients disclosed higher PAF-AH than LAC-negative (22.1 ± 6.4 nmol/min/ml vs. 19.5 ± 4.1 nmol/min/ml; p = 0.0032), and aPL-negative patients (p = 0.03). Patients presenting positive IgG aß2GPI disclosed higher PAF-AH than patients with only IgM aß2GPI-positive antibodies (23.1 ± 7.2 nmol/min/ml vs. 20.1 ± 5.3 nmol/min/ml; p = 0.035), as well as than patients showing only isolated LAC, aCL or aPS/PT (16.9 ± 3.8 nmol/min/ml; p = 0.003). CONCLUSIONS: PAF-AH plasmatic activity is particularly up-regulated in LAC+ and in aß2GPI IgG+ patients, possibly representing an alternative prognostic biomarker for the therapeutic management of APS patients.