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P Ubbiali

Publications and source records attributed to P Ubbiali.

4 recordsLinked to original sources
PubMed1999

Cells with clonal light chains are present in peripheral blood at diagnosis and in apheretic stem cell harvests of primary amyloidosis.

In primary systemic amyloidosis, small numbers of bone marrow plasma cells secrete monoclonal light chains that form extracellular fibrils (amyloid) in various organs. Evidence limited to a few cases suggests that rare clonal elements can also be found in the peripheral blood (PB), and this may be relevant in PB stem cell autotransplantation. Since up to 40% of amyloid clones do not synthesize heavy chains, in order to detect tumor cells with high specificity and sensitivity we developed a seminested allele-specific oligonucleotide polymerase chain reaction for tumor light chains. Clone-related sequences were detected in DNA and/or cDNA from the PB cells of eight of 10 patients at diagnosis and from apheretic collections of three of four cases undergoing PB progenitor autotransplantation. Since there are experimental data suggesting that circulating tumor cells may be involved in the growth of the amyloidogenic clone and may be chemoresistant, these findings are relevant to the use of leukapheresis purging strategies for PB progenitor autotransplantation in amyloidosis.

Adult↗
PubMed1998

Evidence that amyloidogenic light chains undergo antigen-driven selection.

AL amyloidosis is characterized by fibrillar tissue deposits (amyloid) composed of monoclonal light chains secreted by small numbers of indolent bone marrow plasma cells whose ontogenesis is unknown. To address this issue and to provide insights into the processes that accompanied pathogenic light chain formation, we isolated the complete variable (V) regions of 14 light (VL) and 3 heavy (VH) chains secreted by amyloid clones at diagnosis (10 Bence Jones and 4 with complete Igs, 9 lambda and 5 kappa) by using an inverse polymerase chain reaction-based approach free of primer-induced biases. Amyloid V regions were found to be highly mutated compared with the closest germline genes in the databases or those isolated from the patients' DNA, and mutations were not associated with intraclonal diversification. Apparently high usage of the lambdaIII family germline gene V lambdaIII.1 was observed (4 of 9 lambda light chains). Analysis of the nature and distribution of somatic mutations in amyloid V regions showed that there was statistical evidence of antigen selection in 8 of 14 clones (7 in VL and 1 in VH). These results indicate that a substantial proportion of the amyloid clones developed from B cells selected for improved antigen binding properties and that pathogenic light chains show evidence of this selection.

Aged↗
PubMed1997

Membrane CD22 defines circulating myeloma-related cells as mature or later B cells.

Circulating clonally related earlier cells are present in multiple myeloma (MM) and may be involved in the dissemination of this disease, its recurrence, and chemoresistance. The nature, stage of differentiation, and size of this cell population remain uncertain. Unlike other B-cell markers, CD22 membrane expression is limited to the late differentiation stages comprised between mature B cells (CD22+) and plasma cells (PC; CD22-) and may thus be useful in delimiting the maturational state of circulating early myeloma cells. Peripheral blood clone-related cells were detected by anti-idiotypic (Id) monoclonal antibodies and found to express CD22 (92% to 95%), monotypic light and heavy chain (100%), and CD38 (45%), whereas bone marrow PC were CD22-negative. CD22 expression was also documented on functional myeloma PC precursors, defined as peripheral blood cells capable of in vitro cytokine-driven monotypic PC differentiation, because up to approximately 70% inhibition of this process was obtained in 10 myeloma patients through the use of biospecific antibodies (BsAb) that deliver the plant toxin saporin to CD22+ cells. As further evidence of CD22 on circulating abnormal cells, it was found that in the only patient analyzed for DNA content, a portion of the peripheral blood CD22+ cells killed were hyperdiploid. Collectively, these findings indicate that most peripheral blood myeloma PC precursors are mature or later B cells presenting membrane CD22. The pattern of CD22 expression suggests the existence in MM of a differentiation process analogous to the normal antigenic response, in which CD22+ B cells migrate to the bone marrow and lose CD22 with PC differentiation. In addition, the sensitivity of myeloma PC precursors to the cytotoxic effects of the anti-CD22 BsAb and the possibility of interfering with their differentiation have potential therapeutic relevance.

Amyloidosis↗