RESUMO
Malignant plasma cells (PC) in human multiple myeloma (MM) are retained in the bone marrow (BM) microenvironment. Using HUTS21 monoclonal antibody that reacts with active CD29 integrin, we demonstrate that this active form is tightly regulated by divalent cations and soluble CD106 (sCD106) contained in the BM plasma. Moreover, we also show that in vivo expression of the active CD29 on PC was clearly diminished in a minority of MM cases (HUTS21(-) patients). HUTS21(-) cells were refractory to the addition of either normal allogeneic BM plasma or optimal concentrations of exogenous divalent cations and recombinant sCD106. Furthermore, a lower binding to fibronectin was detected in comparison with HUTS21(+) PC. On the other hand, although HUTS21(-) PC showed a reduced amount of total (active+inactive) CD29, western-blot assays demonstrated that these clonal PC contained the two species of CD29, with molecular masses of 110 and 130 kDa, which were expressed on normal or HUTS21(+) PC. Finally, we detected a clear association between the presence of HUTS21(-) PC in the BM and an increased percentage of circulating PC with a high proliferative index, emphasizing the essential role of CD29 in the pathogenesis and progression of this disease.
Assuntos
Medula Óssea/imunologia , Cátions Bivalentes , Proliferação de Células , Integrina beta1/imunologia , Mieloma Múltiplo/patologia , Plasmócitos/imunologia , Molécula 1 de Adesão de Célula Vascular/imunologia , Western Blotting , Humanos , Imunofenotipagem , Mieloma Múltiplo/sangue , Mieloma Múltiplo/imunologia , SolubilidadeAssuntos
Antialérgicos/administração & dosagem , Anticorpos Anti-Idiotípicos/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Teste de Degranulação de Basófilos/métodos , Urticária/tratamento farmacológico , Antialérgicos/uso terapêutico , Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Autoimunidade , Basófilos/efeitos dos fármacos , Basófilos/imunologia , Degranulação Celular/efeitos dos fármacos , Doença Crônica , Monitoramento de Medicamentos/métodos , Resistência a Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Omalizumab , Tetraspanina 30/metabolismo , Resultado do TratamentoRESUMO
An early and accurate diagnosis of multiple sclerosis (MS) is very important, since it allows early treatment initiation, which reduces the activity of the disease. Oligoclonal IgG band (OCGB) detection is a good ancillary tool for MS diagnosis. However, it was argued that its usefulness was limited by the high interlaboratory variability. In the last years, different techniques for OCGB detection have appeared. We performed a blinded aleatorized multicenter study in 19 Spanish hospitals to assess the accuracy and reproducibility of OCGB detection in this new scenario. We studied cerebrospinal fluid (CSF) and serum samples from 114 neurological patients. Every hospital contributed to the study with triplicated pairs of CSF and serum samples of six patients and analyzed 18 different samples. Global analysis rendered a sensitivity of 92.1%, a specificity of 95.1% and a Kappa value of 0.81. This shows that current techniques for OCGB detection have good accuracy and a high interlaboratory reproducibility and thus, represent a good tool for MS diagnosis. When we analyzed separately the different techniques used for OCGB detection, the highest concordance was observed in western blot with alkaline phosphatase detection (kappa=0.91). This indicates that high sensitivity techniques improve the reproducibility of this assay.
