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22.
  • Malmborg Hager, Ann-Christin, et al. (författare)
  • Affinity and Epitope Profiling of Mouse Anti-CD40 Monoclonal Antibodies
  • 2003
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 57:6, s. 517-524
  • Tidskriftsartikel (refereegranskat)abstract
    • The CD40-CD40L interaction plays a critical role in both humoral and cellular immune responses and interfering antibodies have been suggested as an effective approach for the treatment of lymphomas and autoimmune diseases. In this study we have profiled a panel of mouse antihuman CD40 monoclonal antibodies (MoAbs), regarding their CD40 binding affinity and epitope-specificity relative to the CD40L binding in relation to their cellular activating potential. Despite a rather similar domain-recognition profile, the MoAbs blocked the CD40L binding to a varying degree, with MoAb 5C3 being the poorest inhibitor. There was no correlation between affinity and cellular activation potential. In contrast, a correlation between the ability to block CD40L-binding and activation potential could be seen. We believe that this analysis of several mouse anti-CD40 antibodies can be used to develop strategies for producing new human anti-CD40 antibodies that can more effectively induce or block B-cell proliferation.
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23.
  • Oxelius, Vivi-Anne, et al. (författare)
  • Serum Gm Allotype development During Childhood
  • 1999
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 50, s. 440-446
  • Tidskriftsartikel (refereegranskat)abstract
    • Gm allotypes are genetic variants of the immunoglobulin heavy G chains (IGHG) of IgG molecules, coded from chromosome 14q32, characterized by differences in amino acid epitopes of the constant heavy G chains and inherited in the Mendelian manner. Gm allotypes have influence on IgG subclass levels, and serum Gm allotype levels have been given for different Gm genotypes in adults. Four hundred and thirty healthy children, aged 1-15 years, were examined for serum Gm allotypes and IgG subclasses from the six most common Gm genotypes and different age groups were measured using competitive enzyme-linked immunosorbant assay and radial immunodiffusion methods. Quantities (in g/l) of G1m(a) and G1m(f) of IgG1, G2m(n) and G2m(-n) of IgG2 and G3m(g), and G3m(b) of IgG3 are given. Different maturation rates of the alternative Gm allotypes within IgG1, IgG2 and IgG3 were shown. G2m(n) development was strikingly retarded compared with G2m(-n) from the gamma2 locus. This was found comparing IgG2 levels from homozygous G2m(-n-n) and G2m(nn) individuals, but was also seen in heterozygous G2m(n-n) genotypes. From the gamma1 locus G1m(f) levels dominated significantly, but inconstantly, over G1m(a) levels in heterozygous G1m(af) individuals. In homozygous G1m genotypes, G1m(aa) compared with G1m(ff) of the same age, one or the other dominated, sometimes significantly. Serum levels of G3m(b) from the gamma3 locus of homozygous G3m(bb) individuals were increased significantly compared with G3m(g) levels of homozygous G3m(gg) individuals, in ages over 3 years. However, in heterozygous G3m(gb) individuals G3m(b) dominance was not evident. There is a relatively rapid development of G1m(f) molecules and a retarded development of G2m(n) in the Gm(f;n;b) haplotype. In comparison, G1m(a) is retarded and G2m(-n) is enhanced in the Gm(a;-n;g) haplotype. The retarded serum G2m(n) development is comparable with serum IgA development during childhood. Different maturation rates of Gm allotypes within the same IgG subclass provide further explanation for the variation of the antibody response during childhood. Quantitative Gm allotype determinations give information of the activity from IGHG genes. The genetic variation constitutes an additional basis for evaluation of IgG antibodies in different diseases in childhood
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24.
  • Persson, Carl, et al. (författare)
  • Contribution of plasma-derived molecules to mucosal immune defence, disease and repair in the airways
  • 1998
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 47:4, s. 302-313
  • Forskningsöversikt (refereegranskat)abstract
    • This review discusses recent observations, in health and disease, on the release and distribution of plasma-derived molecules in the airway mucosa. Briefly, the new data on airway mucosal exudation mechanisms suggest that the protein systems of plasma contribute significantly to the mucosal biology, not only in injured airways but also in such mildly inflamed airways that lack oedema and exhibit no sign of epithelial derangement. Plasma as a source of pluripotent growth factor, adhesive, leucocyte-activating, etc., molecules may deserve a prominent position in schemes that claim to illustrate immunological and inflammatory mechanisms of the airway mucosa in vivo.
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26.
  • Popovic, M., et al. (författare)
  • Identification of new loci controlling collagen-induced arthritis in mouse using a partial advanced intercross and congenic strains
  • 2008
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 68:4, s. 405-413
  • Tidskriftsartikel (refereegranskat)abstract
    • Collagen-induced arthritis (CIA) is a well studied mouse model of the human disease rheumatoid arthritis (RA). Both CIA and RA are complex diseases affected by multiple genes as well as environmental factors. Identifying the genes that determine susceptibility to arthritis would give invaluable clues to the largely unknown aetiology of RA. In this study, we dissected a known locus, Cia6, as well as a genomic region on chromosome 14 with no previously known arthritis loci, using a partial advanced intercross and a collection of congenic strains. The chromosome 14 congenic fragment, containing the T-cell receptor alpha (Tcra) locus, was included based on the hypothesis that the Cia6 locus is caused by a polymorphism in the Tcr beta (Tcrb) locus and that the two loci interact. Splitting up the congenic fragments revealed multiple loci affecting arthritis traits as well as production of collagen-specific autoantibodies. In total seven new loci were identified of which four were in the previously unlinked chromosome 14 region. Both Tcr loci were within CIA loci making them candidate susceptibility genes. The results demonstrate the importance of breaking up genetic regions in smaller fragments to identify the underlying complex set of loci.
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29.
  • Roth, Bodil, et al. (författare)
  • Pathogenesis of autoimmune diseases: antibodies against transglutaminase, peptidylarginine deiminase and protein-bound citrulline in primary Sjögren's syndrome, multiple sclerosis and Alzheimer's disease.
  • 2008
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 67:6, s. 626-631
  • Tidskriftsartikel (refereegranskat)abstract
    • Coeliac disease (CD) is becoming a model for understanding the pathogenesis of autoimmune disorders. In CD, antibodies against transglutaminase 2 (TG2) and specific residues of gliadins have been identified. A similar situation is seen in rheumatoid arthritis (RA) with both anti-citrullinated protein antibodies (ACPA) and auto-antibodies against the citrullinating enzyme, peptidylarginine deiminase (PAD). Previously, we have suggested that a complex between an enzyme and its modified substrate constitutes the neoantigen in autoimmune diseases. Our hypothesis is challenged by findings in patients of primary Sjögren's syndrome (pSS) who do not express ACPA, but who have been reported to carry anti-PAD. The aims of our investigation were to reproduce the study claiming the presence of anti-PAD in pSS and screen for ACPA and antibodies against TG2 and PAD in pSS (n = 78), multiple sclerosis (MS) (n = 85) and Alzheimer's disease (AD) (n = 79) using ELISA. With blood donors (n = 100) as controls, no increased occurrence of autoantibodies was found among the patient groups tested. Contrary to what has been published previously, patients with pSS do not express anti-PAD. The hypothesis of a complex between an enzyme and its modified substrate constituting the neoantigen in autoimmune diseases is still valid. The prevalence of anti-PAD, anti-TG2 and ACPA is comparatively restricted. PAD and TG2 do not seem to be involved directly in autoimmune mechanisms in pSS, MS or AD.
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30.
  • Salomonsson, S., et al. (författare)
  • A Population-based Investigation of the Autoantibody Profile in Mothers of Children with Atrioventricular Block
  • 2011
  • Ingår i: Scandinavian Journal of Immunology. - Oxford : Blackwell Publishing. - 0300-9475 .- 1365-3083. ; 74:5, s. 511-517
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of the study was to investigate the antigen specificity and occurrence of individual autoantibodies in mothers of children diagnosed with atrioventricular (AV) block in a nation-wide setting. Patients with AV block detected before 15 years of age were identified using national quality registries as well as a network of pediatric and adult cardiologists and rheumatologists at the six university hospitals in Sweden. Patients with gross heart malformations, surgically or infectiously induced blocks were excluded. Blood samples were obtained from the mothers and maternal autoantibody profile, including the occurrence of antibodies against Ro52, Ro60, La, SmB, SmD, RNP-70k, RNP-A, RNP-C, CENP-C, Scl-70, Jo-1, ribosomal RNP and histones was investigated in 193 mothers of children with AV block by immunoblotting and ELISA. Autoantibody reactivity was detected in 48% (93/193) of the mothers of children with AV block. In autoantibody-positive mothers, the vast majority, 95% (88/93), had antibodies against Ro52, while 63% (59/93) had autoantibodies to Ro60 and 58% (54/93) had autoantibodies to La. In addition, 13% (12/93) of the autoantibody-positive mothers had antibodies to other investigated antigens besides Ro52, Ro60 and La, and of these anti-histone antibodies were most commonly represented, detected in 8% (7/93) of the mothers. In conclusion, this Swedish population-based study confirms that maternal autoantibodies may associate with heart block in the child. Further, our data demonstrate a dominant role of Ro52 antibodies in association with AV block.
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