RESUMO
BACKGROUND: Multiple myeloma (MM) is the malignancy with the most frequent expression of the highly immunogenic cancer-testis antigens (CTA), and we have performed the first analysis of longitudinal expression, immunological properties, and fine specificity of CTA-specific antibody responses in MM. METHODS: Frequency and characteristics of antibody responses against cancer-testis antigens MAGE-A3, NY-ESO-1, PRAME, and SSX-2 were analyzed using peripheral blood (N = 1094) and bone marrow (N = 200) plasma samples from 194 MM patients. RESULTS: We found that antibody responses against CTA were surprisingly rare, only 2.6 and 3.1 % of patients evidenced NY-ESO-1- and SSX-2-specific antibodies, respectively. NY-ESO-1-specific responses were observed during disease progression, while anti-SSX-2 antibodies appeared after allogeneic stem cell transplantation and persisted during clinical remission. We found that NY-ESO-1- and SSX-2-specific antibodies were both capable of activating complement and increasing CTA uptake by antigen-presenting cells. SSX-2-specific antibodies were restricted to IgG3, NY-ESO-1 responses to IgG1 and IgG3. Remarkably, NY-ESO-1-positive sera recognized various non-contiguous regions, while SSX-2-specific responses were directed against a single 6mer epitope, SSX-2(85-90). CONCLUSIONS: We conclude that primary autoantibodies against intracellular MM-specific tumor antigens SSX-2 and NY-ESO-1 are rare but functional. While their contribution to disease control still remains unclear, our data demonstrate their theoretic ability to affect cellular anti-tumor immunity by formation and uptake of mono- and polyvalent immune complexes.
Assuntos
Antígenos de Neoplasias/imunologia , Autoanticorpos/imunologia , Transplante de Células-Tronco Hematopoéticas , Proteínas de Membrana/imunologia , Mieloma Múltiplo/imunologia , Proteínas de Neoplasias/imunologia , Proteínas Repressoras/imunologia , Adulto , Idoso , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Ativação do Complemento , Ensaio de Imunoadsorção Enzimática , Epitopos/química , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células K562 , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Reação em Cadeia da Polimerase em Tempo Real , Transplante HomólogoRESUMO
INTRODUCTION: The aim of this study was to determine the percentage of seropositive pregnant women, i.e. of pregnant women infected with Toxoplasma gondii in order to provide an insight into the risk of developing congenital toxoplasmosis in our community. MATERIAL AND METHODS: In the period of two years, 662 pregnant women from Vojvodina were examined serologically. The enzyme-linked immunosorbent assay tests were performed to determine IgM and IgG antibodies against Toxoplasma gondii and the complement fixation test was done to detect total antibodies against Toxoplasma gondii. RESULTS AND DISCUSSION: Seropositivity was determined in 180 pregnant women (27.19%). Of 135 pregnant women examined in the routine control in pregnancy, 16.30% were seropositive and out of five proven, completely new Toxoplasma gondii intfections, three were detected in pregnant women who had undergone the routine check-up for no specific symptoms. A detailed analysis of the frequency of seropositive findings in relation to clinical diagnoses and the place of residence of pregnant women (urban and rural areas) was performed. At the same time, the results from the serological reactions were presented, commented and interpreted, and recommendations were given for the implementation of additional examinations (eg, IgG antibody avidity test) in order to make the accurate diagnosis. CONCLUSION: It can be concluded that the occurrence of congenital toxoplasmosis is still a problem in our community and that the best prevention is the prompt and adequate examination of pregnant women for the presence of Toxoplasma gondii infection.
Assuntos
Complicações Infecciosas na Gravidez/epidemiologia , Toxoplasma/isolamento & purificação , Toxoplasmose/epidemiologia , Adulto , Anticorpos Antiprotozoários/sangue , Testes de Fixação de Complemento , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/imunologia , Resultado da Gravidez , Estudos Soroepidemiológicos , Toxoplasma/imunologia , Toxoplasmose/diagnóstico , Toxoplasmose/imunologiaRESUMO
OBJECTIVE: To evaluate diagnostic value of cystatin C serum levels as alternative marker of renal function in pre-eclamsia (PE) and compare it with the traditional markers of renal function, creatinine and uric acid. In order to investigate the possible influence of inflammation on biochemical markers of renal function, serum levels of high sensitive CRP were measured (hsCRP). METHODS: In this prospective study markers of kidney function were investigated in two groups of pregnant women: one with PE (n = 32) and the other of healthy pregnant women (n = 60). Serum cystatin C levels were measured as well as levels of traditional renal markers creatinin and uric acid and levels of high sensitive C-reactive protein. RESULTS: Serum levels of cystatin C, creatinine and uric acid were significantly higher in the PE group than in the control group. Serum levels of hsCRP were higher in approximately the same number of patients with PE (50%) as in normal pregnancies (40%), without significant differences in CRP values between the two groups of patients. CONCLUSIONS: Cystatin C serum level may have significant role as a marker of pre-eclampsia specially when used in combination with uric acid levels.