AB0193 Antibodies to Hnrnp B1 (RA33) in Patients with Systemic Sclerosis

Maslyanskiy, A.; Roggenbuck, Dirk; Лапин, С. В.; Мазинг, А. В.; Lazareva, N M; Ilivanova, Elena; Kolesova, Ekaterina; Мазуров, В. И.

doi:10.1136/annrheumdis-2014-eular.2222

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“…Objectives: To compare the frequency of anti-hnRNP B1 with other SSc-specific Aab and to determine an association thereof with the clinical phenotype in patients with SSc Methods: We studied Aab prevalence in 64 patients with SSc, 29 with diffuse cutaneous SSc and 26 with limited cutaneous disease as well as 9 patients with overlap syndrome. Diagnosis of SSc in all patients was based on 1980 ACR (ARA) criteria and the disease phenotype was analyzed according to LeRoy's classification criteria [7]. Serum samples from clinically healthy blood donors (n=174) were used as a control group.…”

Section: Discussionmentioning

confidence: 99%

AB0192 Proof of Concept, Self-Organized Criticality Theory of Autoimmunity: Autoantibody-Inducing CD4 T Cell That Causes SLE Belongs to CD45rb-Cd122-Pd1+ Subset

2014

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Background A critical question in elucidating the pathogenesis of SLE or autoimmunity would be how autoreactive clones emerge and expand in the host. According to the prevailing view of autoimmune disease, autoreactive clones may come from either clones that had escaped negative selection in the thymus or clones that have been reactivated from tolerance. However, clones that would emerge by either process would be restricted in their antigen specificity and apparently could not account for the broad T cell receptor (TCR) repertoire and the more than 100 distinct autoantibody specificities found in SLE (Ref 1). We have proposed an alternative novel theory, called the self-organized criticality theory, which explains that systemic autoimmunity necessarily takes place when the host's immune system is overdriven by repeated exposure to antigen, reaching levels that surpass the immune system's stability-limit, i.e., self-organized criticality (Ref 2). We found that a CD4 T cell subset which has passed thru TCRα but not TCRβ revision is generated at peripheral lymphoid organ spleen after heavily repeated immunization with any antigen, and we named this CD4 T cell an “autoantibody-inducing CD4 T cell” (aiCD4 T cell). This aiCD4 T cell not only induced B cells to generate a large variety of autoantibodies, but also promoted final differentiation of CD8 T cells into cytotoxic T lymphocytes (CTL) via antigen cross-presentation, leading to the tissue injuries identical to those seen in SLE. This aiCD4 T cell is functionally indispensable for the pathogenesis of SLE. Objectives We report our recent findings on the distinct cell surface markers that characterize and identify aiCD4 T cells to be CD45RBlo122lo and programmed cell death-1 (PD-1)-positive. Methods BALB/c mice were repeatedly immunized with OVA. To investigate gene expression profiles of aiCD4 T cell, we performed microarray analysis of CD45RBlo122lo CD4 T cell after immunization 12x with OVA. CD45RBlo122lo CD4 T cells were isolated referring to PD-1 expression, and these fractionated cells were adoptively transferred into naïve recipients. Autoantibodies in sera of recipient mice were measured 2 weeks after cell transfer. Results Under microarray analysis, we found that gene expression of PD-1 was increased x2 in the CD45RBlo122lo CD4 subset. Simultaneously, surface expression of PD-1 protein was also significantly increased in this subset. Adoptive cell transfer of PD-1+CD45RBlo122lo CD4 T cells from 12x immunized mice significantly increased both RF and anti-dsDNA antibody in the naïve recipients. Conclusions The aiCD4 T cell that induces SLE belongs to PD-1+CD45RBlo122lo CD4 subpopulation. References Shiozawa S. Joint Bone Spine 79:428, 2012. 2, Tsumiyama K et al. PLoS ONE 4(12): e8382, 2009. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3938

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Section: Discussionmentioning

confidence: 99%