J Nilsson

Publications (4)18.97 Total impact

• Article: Myelin protein P0‐specific IgM producing monoclonal B cell lines were established from polyneuropathy patients with monoclonal gammopathy of undetermined significance (MGUS)

  M. KVARNSTRÖM, E. SIDOROVA, J. NILSSON, C. EKERFELT, M. VRETHEM, O. SÖDERBERG, M. JOHANSSON, A. ROSÉN, J. ERNERUDH
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  ABSTRACT: Monoclonal expansion of B cells and plasma cells, producing antibodies against ‘self’ molecules, can be found not only in different autoimmune diseases, such as peripheral neuropathy (PN), but also in malignancies, such as Waldenström’s macroglobulinaemia and B-type of chronic lymphocytic leukaemia (B-CLL), as well as in precancerous conditions including monoclonal gammopathy of undetermined significance (MGUS). About 50% of patients with PN-MGUS have serum antibodies against peripheral nerve myelin, but the specific role of these antibodies remains uncertain. The aims of the study were to establish, and characterize, myelin-specific B cell clones from peripheral blood of patients with PN-MGUS, by selection of cells bearing specific membrane Ig-receptors for myelin protein P0, using beads coated with P0. P0-coated magnetic beads were used for selection of cells, which subsequently were transformed by Epstein–Barr virus. The specificity of secreted antibodies was tested by ELISA. Two of the clones producing anti-P0 antibodies were selected and expanded. The magnetic selection procedure was repeated and new clones established. The cells were CD5+ positive, although the expression declined in vitro over time. The anti-P0 antibodies were of IgM-λ type. The antibodies belonged to the VH3 gene family with presence of somatic mutations. The IgM reacted with P0 and myelin-associated glycoprotein (MAG), and showed no evidence for polyreactivity, in contrast to other IgM CD5+ clones included in the study as controls. The expanded clones expressed CD80 and HLA-DR, which is compatible with properties of antigen-presenting cells. The immunomagnetic selection technique was successfully used for isolation of antimyelin protein P0-specific clones. The cell lines may provide useful tools in studies of monoclonal gammopathies, leukaemia, and autoimmune diseases, including aspects of antigen-presentation by these cells followed by T cell activation.
  Clinical & Experimental Immunology 03/2002; 127(2):255 - 262. · 3.36 Impact Factor
• Article: Myelin protein P0-specific IgM producing monoclonal B cell lines were established from polyneuropathy patients with monoclonal gammopathy of undetermined significance (MGUS).

  M Kvarnstrom, E Sidorova, J Nilsson, C Ekerfelt, M Vrethem, O Soderberg, M Johansson, A Rosen, J Ernerudh
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  ABSTRACT: Monoclonal expansion of B cells and plasma cells, producing antibodies against 'self' molecules, can be found not only in different autoimmune diseases, such as peripheral neuropathy (PN), but also in malignancies, such as Waldenström's macroglobulinaemia and B-type of chronic lymphocytic leukaemia (B-CLL), as well as in precancerous conditions including monoclonal gammopathy of undetermined significance (MGUS). About 50% of patients with PN-MGUS have serum antibodies against peripheral nerve myelin, but the specific role of these antibodies remains uncertain. The aims of the study were to establish, and characterize, myelin-specific B cell clones from peripheral blood of patients with PN-MGUS, by selection of cells bearing specific membrane Ig-receptors for myelin protein P0, using beads coated with P0. P0-coated magnetic beads were used for selection of cells, which subsequently were transformed by Epstein--Barr virus. The specificity of secreted antibodies was tested by ELISA. Two of the clones producing anti-P0 antibodies were selected and expanded. The magnetic selection procedure was repeated and new clones established. The cells were CD5+ positive, although the expression declined in vitro over time. The anti-P0 antibodies were of IgM-lambda type. The antibodies belonged to the VH3 gene family with presence of somatic mutations. The IgM reacted with P0 and myelin-associated glycoprotein (MAG), and showed no evidence for polyreactivity, in contrast to other IgM CD5+ clones included in the study as controls. The expanded clones expressed CD80 and HLA-DR, which is compatible with properties of antigen-presenting cells. The immunomagnetic selection technique was successfully used for isolation of antimyelin protein P0-specific clones. The cell lines may provide useful tools in studies of monoclonal gammopathies, leukaemia, and autoimmune diseases, including aspects of antigen-presentation by these cells followed by T cell activation.
  Clinical & Experimental Immunology 03/2002; 127(2):255-62. · 3.36 Impact Factor
• Article: Abnormalities in T-lymphocyte populations in blood from patients with demyelinating polyneuropathy associated with monoclonal gammopathy.

  M Vrethem, C Dahle, C Ekerfeldt, J Nilsson, B Ekstedt, J Ernerudh
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  ABSTRACT: Patients with monoclonal gammopathy secrete monoclonal antibodies (M-component), that in some patients are associated with polyneuropathy. The M-component has been shown to react with peripheral nerve myelin in some of these patients. However, it is not known whether the M-component secreting B-cells are autonomous or subject to regulation by T-cells or if other cellular abnormalities may occur. In order to define circulating lymphocyte subpopulations, flow cytometry was done on blood samples from patients with monoclonal gammopathy and demyelinating polyneuropathy (n = 13) and patients with monoclonal gammopathy without polyneuropathy (n = 11), and were compared to healthy controls. Significantly increased proportions of primed T-helper (CD4+) cells, i.e. those expressing helper/inducer function (CD29+ CD4+), providing help for antibody secretion, as well as decreased proportions of naive, unprimed suppressor/inducer (CD45RA+ CD4+) T-helper cells were found in patients with M-component associated polyneuropathy. Within the T-cytotoxic/suppressor population (CD8+) we found an increased proportion of killer/effector (S6F1+ CD8+) cells and a decreased proportion of suppressor/effector (S6F1- CD8+) cells in patients with monoclonal gammopathy and polyneuropathy. Similar findings were found in monoclonal gammopathy patients without polyneuropathy, although the deviations in general were less pronounced and did not reach statistical significance compared to the controls. The proportion of natural killer (NK) cells (CD56+) was markedly decreased in all patients with monoclonal gammopathy. In the whole group of patients with monoclonal gammopathy, we found clear proportions of interleukin-2 receptor (CD25+) expressing lymphocytes, indicating the presence of activated T-cells. No clear correlation between abberations in T-cell subtypes and clinical severity of the demyelinating polyneuropathy or titres of anti-PNM antibodies was found.(ABSTRACT TRUNCATED AT 250 WORDS)
  Journal of the Neurological Sciences 05/1994; 122(2):171-8. · 2.35 Impact Factor
• Article: Thioredoxin prolongs survival of B-type chronic lymphocytic leukemia cells

  J. Nilsson, O. Soderberg, K. Nilsson, A. Rosen
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  ABSTRACT: Thioredoxin (Trx) is a ubiquitous protein disulfide oxidoreductase with antioxidant, cytokine, and chemotactic properties. Previously, we showed that Trx, in synergy with interleukin 1 (IL-1), IL-2, IL-4, tumor necrosis factor alpha (TNF-alpha), and CD40-ligation induced S-phase entry and mitosis in normal B cells and B-type chronic lymphocytic leukemia (B-CLL) cells. The viability of B-CLL cells stimulated by these protocols is high, and it has been hypothesized that the overexpression of Bcl-2 found in B-CLL protects the cells from apoptosis in vitro and in vivo. In this study, we have analyzed the response of cells derived from 12 samples of patients with B-CLL to recombinant human Trx in spontaneous apoptosis, with special reference to the Bcl-2 expression. Long-term cultures of B-CLL clones showed significantly higher viability when supplemented with human Trx (P =.031), also exemplified with clones surviving more than 2 months. Short-term cultures of B-CLL cells exposed to 1 microg/mL of Trx for 1, 5, or 12 days maintained expression or delayed down-regulation of Bcl-2 compared with control cultures containing RPMI 1640 medium and 10% fetal calf serum only (P =.032,. 002,.026, respectively). All B-CLL cells expressed constitutive Trx at varying but low levels, in contrast to adult T-cell leukemias, which overexpress Trx, as previously reported. We found that Trx added to B-CLL cells increased in a dose-dependent fashion the release of TNF-alpha, which has been suggested to be an autocrine growth factor for these cells. In conclusion, we have found that human recombinant Trx induced TNF-alpha secretion, maintained Bcl-2, and reduced apoptosis in B-CLL cells. (Blood. 2000;95:1420-1426)
  Blood 95(4):1420-6. · 9.90 Impact Factor