Plasma proteomic and autoantibody profiles reveal the proteomic characteristics involved in longevity families in Bama, China.

BACKGROUND: Chinese Bama Yao Autonomous County is a well-known longevity region in the world. In the past 30 years, population and genome studies were undertaken to investigate the secret of longevity and showed that longevity is the result of a combination of multiple factors, such as genetic, environmental and other causes. In this study, characteristics of the blood plasma proteomic and autoantibody profiles of people from Bama longevity family were investigated. METHODS: Sixty-six plasma donors from Chinese Bama longevity area were recruited in this study. Thirty-three offsprings of longevous families were selected as case studies (Longevous group) and 33 ABO (blood type), age, and gender-matched subjects from non-longevous families were selected as controls (Normal group). Each group contains 3 biological replicates. Tandem mass tag-based proteomic technique was used to investigate the differentially expressed plasma proteins between the two groups. The auto-reactive IgG antibody profiles of the 3 pooled samples in each group were revealed by human proteome microarrays with 17,000 recombinant human proteins. RESULTS: Firstly, 525 plasma proteins were quantified and 12 proteins were discovered differentially expressed between the two groups. Secondly, more than 500 proteins were recognized by plasma antibodies, 14 proteins ware differentially reacted with the autoantibodies in the two groups. Bioinformatics analysis showed some of the differential proteins and targeted autoantigens were involved in cancer, cardiovascular disease and immunity. CONCLUSIONS: Proteomic and autoantibody profiles varied between the offspring of longevous and normal families which are from the same area and shared the same environmental factors. The identified differences were reported to be involved in several physiological and pathological pathways. The identified proteins will contribute to a better understanding of the proteomic characteristics of people from Bama longevous area and a revelation of the molecular mechanisms of longevity.

Early detection of hepatocellular carcinoma using autoantibody profiles from a panel of tumor-associated antigens.

BACKGROUND: Multiple antigen miniarrays used for detecting autoantibodies to tumor-associated antigens (TAAs) can be a useful approach for cancer detection and diagnosis. We here address a very specific question: might there be autoimmune responses to TAAs which precede clinical detection of hepatocellular carcinoma (HCC) in HBV and HCV chronic liver disease patients under continuous medical surveillance, and if so, could these anti-TAAs be added to the armamentarium of diagnostic tests? METHODS: We here examine the utility of a panel of 12 TAAs for the diagnosis of hepatocellular carcinoma (HCC). We derived a predictive rule for the presence of HCC based on the panel, from a cohort comprising 160 HCC patients and 90 normals. We then applied this rule to sequential anti-TAA data from a cohort of 17 HCC patients, from whom this information was available prior to diagnosis. RESULTS: The predictors (autoantibodies to HCC1, P16, P53, P90, and survivin) indicated the presence of HCC prior to diagnosis in 16 of the 17 patients, at a median lead time of 0.75 year. CONCLUSIONS: We believe these findings warrant further study of anti-TAA profiles as biomarkers for primary or early diagnosis of HCC.

Analysis of autoantibody profiles in osteoarthritis using comprehensive protein array concepts.

Osteoarthritis (OA) is the most common rheumatic disease and one of the most disabling pathologies worldwide. To date, the diagnostic methods of OA are very limited, and there are no available medications capable of halting its characteristic cartilage degeneration. Therefore, there is a significant interest in new biomarkers useful for the early diagnosis, prognosis, and therapeutic monitoring. In the recent years, protein microarrays have emerged as a powerful proteomic tool to search for new biomarkers. In this study, we have used two concepts for generating protein arrays, antigen microarrays, and NAPPA (nucleic acid programmable protein arrays), to characterize differential autoantibody profiles in a set of 62 samples from OA, rheumatoid arthritis (RA), and healthy controls. An untargeted screen was performed on 3840 protein fragments spotted on planar antigen arrays, and 373 antigens were selected for validation on bead-based arrays. In the NAPPA approach, a targeted screening was performed on 80 preselected proteins. The autoantibody targeting CHST14 was validated by ELISA in the same set of patients. Altogether, nine and seven disease related autoantibody target candidates were identified, and this work demonstrates a combination of these two array concepts for biomarker discovery and their usefulness for characterizing disease-specific autoantibody profiles.

Combinaciones de autoanticuerpos y su asociación con variables clínicas en artritis reumatoidea / Combinations of autoantibodies and their association with clinical variables in rheumatoid arthritis / Combinações de autoanticorpos e sua associação com variáveis clínicas na artrite reumatóide

Se evaluó la relevancia clínica de analizar conjuntamente dos nuevos autoanticuerpos (anti-vimentina citrulinada mutada: anti-MCV y anti-peptidil arginina desaminasa 4: anti-PAD4) en conjunto con los utilizados clásicamente en el diagnóstico (factor reumatoideo: FR y anticuerpos contra péptidos citrulinados cíclicos de la anti-CCP) en la artritis reumatoidea (AR). Los autoanticuerpos se determinaron mediante ensayos inmunoenzimáticos en suero de 370 pacientes con AR y 200 controles. Se observó que los anticuerpos anti-MCV presentaron la mayor especificidad de todos los analizados (100%), mientras que los anticuerpos anti-PAD4 presentaron la menor sensibilidad (24%) y especificidad (95%). El 4% de los individuos seronegativos a FR y anti-CCP fue seropositivo a anti-MCV o PAD4. Los pacientes triples seropositivos (FR, anti-CCP y anti-MCV) presentaron mayor inflamación sistémica/articular y actividad clínica que los que expresaron otras combinaciones de autoanticuerpos (p<0,001). Por otra parte, los pacientes sólo positivos a FR cursaron con menor inflamación y actividad clínica (p<0,001). En conclusión, la inclusión de los anticuerpos anti-MCV al panel utilizado para el diagnóstico de la AR (FR y anti-CCP) podría mejorar el diagnóstico oportuno de los individuos, principalmente en aquellos pacientes seronegativos a FR y anti-CCP. Por otra parte, existen perfiles de autoanticuerpos asociados a la actividad clínica de los pacientes.

In this paper it was evaluated the clinical relevance of analyzing together two new autoantibodies (anti-mutated citrullinated vimentin: anti-MCV and anti-peptidyl arginine deiminase type 4: anti-PAD4) and those used classically in the diagnosis (rheumatoid factor: RF and antibodies against cyclic citrullinated peptide: anti-CCP) of rheumatoid arthritis (RA). The autoantibodies were examined by immunoenzymatic assays in sera of 370 patients with RA and 200 controls. It was observed that anti-MCV antibodies have the highest level of specificity of all the analyzed (100%), while the anti-PAD4 antibodies have the lowest sensitivity (24%) and specificity (95%). Four percent of the individuals that were seronegative for RF and anti-CCP were seropositive for anti-MCV or PAD4. Triple seropositive patients (RF, anti-CCP, and anti-MCV) have greater systemic/ joint inflammation and clinical activity than those with other combinations of autoantibodies (p<0.001). Patients who are only positive for FR had less inflammation and clinical activity (p<0.001). In conclusion, the inclusion of anti-MCV antibodies into the panel used for the diagnosis of RA (RF and anti-CCP) could improve the early diagnosis of individuals, mainly in patients that were seronegative for RF and anti-CCP. On the other hand, there are profiles of autoantibodies associated with the clinical activity of RA patients.

O objetivo deste estudo foi avaliar a relevância clínica de analisar dois novos autoanticorpos (anti-vimentina citrulinada mutada: anti-MCV e anti-peptidilarginina deiminase 4: anti-PAD4) e os convencionalmente utilizados no diagnóstico (fator reumatóide: FR e anticorpos contra peptídeos citrulinados cíclicos: anti-CCP) da artrite reumatóide (AR). Os autoanticorpos foram avaliados através de ensaios imunoenzimáticos em soro de 370 doentes com AR e 200 controles. Foi observado que os anticorpos anti-MCV apresentaram o maior grau de especificidade de todos os analisados (100%), enquanto que os anticorpos anti-PAD4 apresentaram a menor sensibilidade (24%) e especificidade (95%). Quatro por cento dos indivíduos soronegativos para FR e anti-CCP foram soropositivos para anti-MCV ou PAD4. Os doentes tríplice soropositivos (FR, anti-CCP e anti-MCV) apresentam maior inflamação sistêmica/articular e atividade clínica do que aqueles com outras combinações de autoanticorpos (p<0.001). Os doentes apenas positivos para FR apresentaram menor inflamação e atividade clínica (p<0.001). Em conclusão, a inclusão dos anticorpos anti-MCV para o painel utilizado para o diagnóstico de AR (FR e anti-CCP) poderia melhorar o diagnóstico oportuno dos indivíduos, principalmente daqueles que são soronegativos para FR e anti-CCP. Por outro lado, existem perfis de autoanticorpos associados à atividade clínica de doentes.