We assessed the diagnostic value of anti-mutated citrullinated vimentin antibodies (anti-MCV) and compared it with those of anti-cyclic citrullinated peptide antibodies (anti-CCP), IgA (ARF), IgM (MRF) and IgG (GRF) rheumatoid factors for rheumatoid arthritis (RA). Serum samples of 170 RA patients, with early and established RA, and 309 controls were tested for anti-MCV, anti-CCP, ARF, MRF and GRF using commercially available ELISA kits. Cut off of different tests was determined with ROC curves. The sensitivity and the specificity of anti-MCV were 74.1 and 79%, respectively. Sixty-five of 309 (21%) controls were anti-MCV positive. Sensitivity and specificity of anti-CCP were 72.4 and 96.1%, respectively. Only 12 of 309 (3.9%) controls were anti-CCP positive. Sensitivity of ARF, MRF and GRF were 64.1, 65.9 and 68.2%, respectively. Their specificity was 79.6, 74.4 and 68.9%, respectively. No significant association was observed between the antibodies tested and extrarticular manifestations. Anti-MCV shows comparable sensitivity but lower specificity than that of anti-CCP. They do not appear to be very useful in the diagnosis of RA.

Summary:In order to evaluate the impact of HLA-DBP1 incompatibilities on the occurrence of acute graft-versus-host disease (GVHD) in unrelated hematopoietic cell transplantation, we studied 57 donor/recipient pairs characterized by their allelic identity for HLA-A, B, C, DRB1 and DQB1 and also for DRB3, 4, 5 loci and aimed to correlate DPB1 mismatches to already described risk factors for GVHD using multivariate Cox regression analysis. DPB1 identity between donor and recipient was observed in 24% and DPB1 compatibility (GVHD vector) in 42%. Two factors were independently associated with severe acute GVHD: two DP incompatibilities (RR = 8.25, 95% confidence interval (CI): 1.67-40.10, P = 0.010) and disease risk (RR = 10.23, 95% CI: 1.12-93.13, P = 0.012). Two DPB1 incompatibilities appeared also to be a factor in poorer survival independent of its effect on acute GVHD (RR = 4.97, 95% Cl: 1.80-13.71, P = 0.002). A correlation between acute GVHD and matching for each individual DPB1 polymorphic region and for residue 69 of the DP␤ molecule, which seems to be a key residue in the alloimmune response, was not observed. Our data indicate that the outcome of unrelated hematopoietic cell transplantation in terms of GVHD but also survival, could be improved through HLA-DPB1 matching or at least by avoiding two DPB1 mismatches. Bone Marrow Transplantation (2002) 30, 497-502. doi:10.1038/sj.bmt.1703658 Keywords: HLA-DPB1; unrelated donor; acute graft-versus-host-disease; survivalThe outcome of hematopoietic cell transplantation from unrelated donors remains poorer than sibling bone marrow transplantation (BMT). This difference is related to an HLA matching between donors and recipients is the major factor influencing the outcome of allogeneic BMT. Unrelated donor selection generally relies on matching for HLA-A, -B, -C, -DRB1 and -DQB1, but does not consider HLA-DP. With a complete HLA identity for these five loci between donors and recipients, HLA DPB1 disparity is observed in 60-70% of these cases. This is accounted for by the extreme polymorphism of DP genes (85 DPB1 alleles coding for 78 different DP␤1 chains) and for the weak or absent linkage disequilibrium between DP and DR-DQ loci.HLA-DP molecules are MHC class II molecules from a structural point of view and can present peptides to T cells, 2 thereby provoking T cell responses. Nonetheless, the role of the HLA-DP in unrelated transplantation has been controversial and remains ill-defined. Several studies 3-8 aimed to correlate DPB1 mismatches with acute GVHD and survival with conflicting results. However, a recent publication using full molecular HLA typing 9 showed an important role of HLA-DP in the alloimmune response.In this study, we aimed to correlate DPB1 mismatches to already described risk factors of acute GVHD using a multivariate Cox regression analysis. For this purpose, we studied 57 donor/recipient transplant pairs fully matched for the alleles HLA-A, B, C, DRB1 and DQB1 and also for the alleles DRB3, 4 and 5 in order to eliminate the alloimmune impa...

The IRAK1 rs3027898 was not associated with RA, whereas C allele of miR-146a rs2910164 was found to be protective. Functional studies are required to investigate the exact role of miR-146a rs2910164 during RA.

Previous studies have indicated that neopterin is synthesized in vitro by human monocyte-derived macrophages and dendritic cells upon stimulation with gamma interferon (IFN-␥). Neopterin production under specific conditions in vitro has also been obtained upon stimulation with IFN-␣ and/or IFN-␤. However, it is unknown if any IFN-␥-independent neopterin synthesis is possible in vivo. In the present study we investigated the serum neopterin concentrations in patients affected by the syndrome of Mendelian susceptibility to mycobacterial disease (MSMD). Indeed, this syndrome is characterized by deeply impaired or absent IFN-␥ production or function due to severe mutations in molecules involved in IFN-␥/interleukin-12 (IL-12)/IL-23-dependent pathway. Serum neopterin levels were measured by an enzyme-linked immunosorbent assay in 27 patients with MSMD. We found that serum neopterin levels are elevated in the complete absence of IFN-␥ activity due either to a complete deficiency of its receptor or to deleterious mutations of IL-12 or its receptor. These data clearly indicate that, as reported from in vitro studies, other stimuli are able to induce neopterin synthesis in vivo. Consequently, neopterin cannot be used as means of diagnosis of MSMD due to IFN-␥-, IL-12-, and IL-23-dependent pathway defects.

CD1 gene (CD1A to CD1E) products are involved in non-peptide antigen presentation, such as lipids and glycolipids, to T cells. With a similar function to MHC, namely antigen presentation, these genes nevertheless displayed a much lower level of polymorphism as compared to MHC. We report here two additional CD1E variants identified in black African individuals, designated herein CD1E*05 and CD1E*06. While the former differs from the common (wild type) allele sequence by two substitutions at nucleotide positions 217 and 229 of exon 2, the latter only by a single base change at position 91 of exon 3. These substitutions lead to amino acid changes at position 73 and 77 of the alpha1 domain in the former and at position 30 of the alpha2 domain in the latter. Identification of these additional variants suggests that the CD1 locus, especially the CD1E gene, is much more polymorphic than previously assumed.