Anti-BiP antibody levels in juvenile idiopathic arthritis (JIA)

The original article can be found at: http://rheumatology.oxfordjournals.org/archive/ Copyright British Society for Rheumatology DOI: 10.1093/rheumatology/keh186 [Full text of this article is not available in the UHRA]We have previously described the human heat shock protein BiP (immunoglobulin binding protein; glucose regulated protein 78) as an autoantigen in rheumatoid arthritis [1]. Antibodies to BiP have been described in the serum of RA patients by ourselves and other groups [2, 3] and we have recently described anti-BiP antibodies in the synovial fluid of RA patients and the serum of patients with primary Sjögren's syndrome [3]. Moreover anti-BiP antibodies have been shown to be elevated in animal models of arthritis [1].Peer reviewe

Stromal cell-derived factor 1 (CXCL12) induces human cell migration into human lymph nodes transplanted into SCID mice

Stromal cell-derived factor 1 (SDF-1; CXCL12), a CXC chemokine, has a primary role in signaling the recruitment of hemopoietic stem cell precursors to the bone marrow during embryonic development. In postnatal life, SDF-1 is widely expressed and is induced in chronically inflamed tissues such as psoriatic skin and the rheumatoid synovium, but has also been implicated in the migration of lymphocytes to lymphoid organs. To investigate the role of SDF-1 in recirculation and homing in vivo, we have developed a model in which human peripheral lymph nodes (huPLN) are transplanted into SCID mice. We have shown that huPLN transplants are viable, vascularized by the murine circulation that forms functional anastomoses with transplant vessels. In addition, grafts retain some features of the pretransplantation tissue, such as lymphoid follicles, lymphatic and high endothelial venule markers. We also show that SDF-1 is capable of inducing the migration of a SDF-1-responsive cell line (U937) and human PBLs from the murine circulation into the grafts in a dose-dependent manner, inhibitable by CXCR4 blockade. The mechanism of action of SDF-1 in this model is independent from that of TNF-alpha and does not rely on the up-regulation of adhesion molecules (such as ICAM-1) on the graft vascular endothelium. This is the first description of huPLN transplantation into SCID mice and of the functional effects of SDF-1 in regard to the migration of human cells into huPLN in vivo. This model provides a powerful tool to investigate the pathways involved in cell migration into lymphoid organs and potentially to target them for therapeutic purposes

Genetic polymorphism of IL-12 p40 gene in immune-mediated disease

Understanding of the genetic basis of autoimmune diseases is currently incomplete. Cytokine gene polymorphisms warrant consideration as factors explaining variation in the human immune and inflammatory responses and as candidate susceptibility genes for related pathological states. Interleukin 12 (IL-12) is a key regulator of the polarisation of immune responses to T helper 1 or 2 categories and plays a role in autoimmune and infectious diseases. Using a bioinformatic strategy, we aligned cDNA and expressed sequence tag sequences to identify putative polymorphic regions of the IL-12 p40 gene. Position 1188 in the 3′ untranslated region (UTR) was polymorphic with the frequency of the common allele around 80% in healthy UK Caucasoids. PCR genotyping of multiple Caucasoid groups and an African group showed significant population variation. In a case-control design, the polymorphism was not associated with rheumatoid arthritis, Felty's syndrome or large granular lymphocyte syndrome with arthritis or multiple sclerosis. A nonsignificant increase in the B allele frequency was observed in the rare large granular lymphocyte syndrome without arthritis (odds ratio 2.02 95% Cl 0.95-4.3). This new genetic marker could be useful in anthropological studies and should be investigated in other autoimmune, allergic, inflammatory and infectious diseases