| 1. |
- Martinsson, Klara, et al.
(författare)
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The effect of activating and inhibiting Fc-receptors on murine mercury-induced autoimmunity.
- 2008
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 31:1, s. 22-29
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Tidskriftsartikel (refereegranskat)abstract
- Fc-receptors for IgG (Fc gamma R) link cellular and humoral immune responses, controlling the balance between activating and inhibitory immune responses, and are involved in autoimmune diseases. Mercury (Hg) induces an autoimmune condition in genetically (H-2(s,q,f)) susceptible mice characterized by lymphoproliferation, hypergammaglobulinemia and IgG antinucleolar antibodies (ANoA). Here we investigate the role of activating (Fc gamma RI, Fc gamma RIII) and inhibitory (Fc gamma RIIb) Fc-receptors on mercury-induced autoimmunity (HgIA) using DBA/1 mice (H-2(q))(-) with targeted Fc gamma R mutations and wild type (wt) mice. Mice deficient for the FcR gamma-chain or FcyRIII and treated with 15 mg/L HgCl2 showed a delayed and attenuated IgG1, IgG2a and IgG2b ANoA response compared to wt mice. Female Hg-treated FcyRIIB(-/-) mice showed a significant increased of lgG2b ANoA development compared to wt mice. The total serum IgG1 response due to Hg was attenuated in FcR gamma(-/-) and Fe gamma RIII-/- mice compared to wt mice. Hg-treated Fc gamma RIIB-/- mice showed an increase of both serum IgG1 and IgE compared to wt mice. We conclude that FcyRIII is of importance for the rapidity and final strength of the ANoA response and the increase in serum IgG1 in HgIA, while lack of Fc gamma RIIb increases the IgG2b ANoA response and the serum IgG1 and IgE response.
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| 2. |
- Berryman, Meghan A., et al.
(författare)
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Autoimmune-associated genetics impact probiotic colonization of the infant gut
- 2022
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Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 133
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Tidskriftsartikel (refereegranskat)abstract
- To exemplify autoimmune-associated genetic influence on the colonization of bacteria frequently used in probiotics, microbial composition of stool from 1326 one-year-old infants was analyzed in a prospective general-population cohort, All Babies In Southeast Sweden (ABIS). We show that an individual's HLA haplotype composition has a significant impact on which common Bifidobacterium strains thrive in colonizing the gut. The effect HLA has on the gut microbiome can be more clearly observed when considered in terms of allelic dosage. HLA DR1-DQ5 showed the most significant and most prominent effect on increased Bifidobacterium relative abundance. Therefore, HLA DR1-DQ5 is proposed to act as a protective haplotype in many individuals. Protection-associated HLA haplotypes are more likely to influence the promotion of specific bifidobacteria. In addition, strain-level differences are correlated with colonization proficiency in the gut depending on HLA haplotype makeup. These results demonstrate that HLA genetics should be considered when designing effective probiotics, particularly for those at high genetic risk for autoimmune diseases.
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| 3. |
- Henriksson, Elisabet Welin, 1960-, et al.
(författare)
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Autoepitope-mapping of the U1-70K protein with human-Drosophila chimeric proteins
- 1997
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Ingår i: Journal of Autoimmunity. - : Academic Press. - 0896-8411 .- 1095-9157. ; 10:6, s. 559-568
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Tidskriftsartikel (refereegranskat)abstract
- The 70K protein is the major autoantigen for anti-RNP autoantibodies directed against the U1 small nuclear ribonucleoprotein complex particle. The U1-70K protein has been epitope-mapped by various groups, and a major antigenic region of about 70 amino acids has been found which overlaps with the RNA binding motif. Attempts to map the major antigenic region further with smaller cloned fragments or with peptides have been hampered by total loss of, or strongly reduced, antigenicity. Thus the major antigenic region is composed of conformational epitopes and a detailed analysis of particular epitopes has not been possible. In the present work, we examine the antigenicity of chimeric proteins assembled from the highly conserved Drosophila melanogaster 70K proteins grafted with human 70K segments. With this approach, the effects on antigenicity of exchanging particular segments can be assayed with the overall structure of the major antigenic domain kept relatively constant. Our results, supported by depletion experiments, show that residues 99-128 from the human protein are essential for recognition by both human and canine anti-RNP autoantibodies. These residues have to be presented in a manner that allows correct conformational interaction between the different protein domains.
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| 4. |
- Henriksson, Elisabet Welin, 1960-, et al.
(författare)
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Human anti-RNP sera contain both human-specific and cross-reactive anti-70K autoantibodies
- 1996
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Ingår i: Journal of Autoimmunity. - : Academic Press. - 0896-8411 .- 1095-9157. ; 9:4, s. 551-559
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Tidskriftsartikel (refereegranskat)abstract
- The U1 snRNP (small nuclear ribonucleoprotein complex) associated 70K protein is the main autoantigen for the anti-RNP autoantibodies which are directed against the U1 snRNP particle. The major antigenic region of the 70K protein has by various laboratories been mapped to an RNA binding domain required for the 70K-U1 snRNA interaction. We have used recombinant proteins comprising this region from the human and the Drosophila melanogaster 70K proteins to examine the species specificity of the human anti-70K autoantibodies found in 42 patient sera. Most, but not all, anti-70K positive sera in this cross-sectional sample contained both human 70K specific anti-bodies and Drosophila 70K reactive antibodies. Results of a longitudinal follow-up of 14 patients indicated that the cross-reactive anti-70K antibodies developed secondarily to the establishment of a species-specific anti-70K reaction. In a fraction of the patient sera this broadening of the response never occurred. Taken together, the data in this study support the hypothesis that the endogenous human 70K protein is the immunogen driving the production of anti-70K autoantibodies.
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| 5. |
- Leijon, Kristina, 1967-, et al.
(författare)
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Specific destruction of islet transplants in NOD‹–›C57BL/6 and NOD‹–›C3H/Tif embryo aggregation chimeras irrespective of allelic differences in beta-cell antigens
- 1995
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Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 8:3, s. 347-356
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Tidskriftsartikel (refereegranskat)abstract
- We have tested the hypothesis that allelic differences in the antigens expressed by the beta-cells of the islets of Langerhans influence the development of insulitis in the non-obese diabetic (NOD) mouse. Islets of Langerhans from NOD, C57BL/6 and C3H/Tif mice were transplanted under the kidney capsule of NOD<-->C57BL/6 and NOD<-->C3H/Tif embryo aggregation (EA) chimeras and the infiltration was scored 5-7 weeks later. Mononuclear cell infiltration of pancreatic islets was observed in 60% of the NOD<-->C57BL/6 and in 55% of the NOD<-->C3H/Tif EA chimeras. All transplanted EA chimeras that developed insulitis also displayed mononuclear cell infiltrates in the transplants, irrespective of the origin of the transplanted islets. In contrast, no infiltration of transplants was detected in EA chimeras scoring negative for insulitis. These results demonstrate that the specific destruction of islet transplants does not require the expression of NOD specific antigens by the islets. Moreover, the beta-cell destruction appears not to be restricted to NOD-MHC. The correlation between insulitis and transplant beta-cell destruction suggests the possibility that the development of insulitis is a prerequisite for transplant specific destruction. MHC restricted destruction may, therefore, precede the beta-cell destruction of transplanted islets. The chimerism among the mononuclear cells infiltrating the islet transplants was found to correlate with the overall haematopoetic chimerism in each of the individual EA chimeras. This observation suggests that NOD bone marrow, as well as non-NOD bone marrow, generates cells contributing to the beta-cell destruction process.
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| 6. |
- Palm, Anna-Karin E., 1983-, et al.
(författare)
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Marginal zone B cells : From housekeeping function to autoimmunity?
- 2021
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Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 119
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Tidskriftsartikel (refereegranskat)abstract
- Marginal zone (MZ) B cells comprise a subset of innate-like B cells found predominantly in the spleen, but also in lymph nodes and blood. Their principal functions are participation in quick responses to blood-borne pathogens and secretion of natural antibodies. The latter is important for housekeeping functions such as clearance of apoptotic cell debris. MZ B cells have B cell receptors with low poly-/self-reactivity, but they are not pathogenic at steady state. However, if simultaneously stimulated with self-antigen and pathogen- and/or damageassociated molecular patterns (PAMPs/DAMPs), MZ B cells may participate in the initial steps towards breakage of immunological tolerance. This review summarizes what is known about the role of MZ B cells in autoimmunity, both in mouse models and human disease. We cover factors important for shaping the MZ B cell compartment, how the functional properties of MZ B cells may contribute to breaking tolerance, and how MZ B cells are being regulated.
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| 7. |
- Svanberg, Cecilia, et al.
(författare)
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Conformational state of C-reactive protein is critical for reducing immune complex-triggered type I interferon response: Implications for pathogenic mechanisms in autoimmune diseases imprinted by type I interferon gene dysregulation
- 2023
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Ingår i: Journal of Autoimmunity. - : ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. - 0896-8411 .- 1095-9157. ; 135
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Tidskriftsartikel (refereegranskat)abstract
- Presence of autoantibodies targeting nuclear constituents, i.e., double-stranded DNA and small nuclear ribonu-cleoproteins (snRNPs), remain a cornerstone in systemic lupus erythematosus (SLE). Fc gamma receptor IIa (Fc gamma RIIa) dependent uptake of nucleic acid containing immune complexes (ICs) by plasmacytoid dendritic cells (PDCs) can activate toll-like receptors (TLRs) such as TLR7 and TLR9 resulting in type I interferon (IFN) production. Pre-viously, the classical liver-derived acute-phase reactant C-reactive protein (CRP) has been suggested to reduce IC -induced type I IFN production, whereas monomeric (mCRP) vs. pentameric (pCRP) mediated effects have not yet been unraveled. Herein, peripheral blood mononuclear cells (PBMCs) or enriched blood DCs from healthy vol-unteers were stimulated with SLE sera, snRNP-IgG (ICs), or TLR ligands with or without pCRP, mCRP, or anti- Fc gamma RIIa antibody. Type I IFNs and cytokine responses were investigated using quantitative PCR, ELISA, and flow cytometry. pCRP inhibited IFN gene expression in PBMCs and enriched DCs after incubation with ICs, compared to ICs alone, whereas mCRP had significantly less inhibitory effect. The effect was independent on the order in which IC or CRP was added to the cells. In addition, pCRP inhibited IFN induced by other TLR stimulators, implicating broader inhibitory effects induced by pCRP. We demonstrate pronounced immunoregulatory functions of CRP whereas the inhibitory properties were evidently dependent on CRPs intact conformational state. The inhibition of type I IFNs was not due to competition of Fc gamma Rs, or binding of CRP to the ICs. Our findings have implications for autoimmune IC-mediated conditions imprinted by type I IFN gene dysregulation.
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