Genetic associations between rheumatoid arthritis and specific HLA class II genes provide clues to understanding the molecular basis for disease susceptibility. There is a remarkable structural relationship among different rheumatoid arthritis (RA) susceptibility genes, in which each of the associated class II alleles encodes a sequence of key amino acids termed the 'shared epitope.' Mechanistic models to account for the shared epitope association with RA can be interpreted in the context of an HLA-directed pathway for the development of disease. We suggest that altered T cell activation results from recognition of the shared epitope, providing a potential mechanism by which the shared epitope may be involved in the generation or modulation of self-recognition during antigen presentation and processing. We propose that the shared epitope association with RA is not solely based on a specific peptide binding motif and peptide determinant selection but rather is influenced by a strongly biased direct recognition of shared epitope residues by direct T cell contact. 1. Nepom GT: Major histocompatibility complex-directed susceptibility to rheumatoid arthritis.

Although evidence shows depressed moods enhance risk for somatic diseases, molecular mechanisms underlying enhanced somatic susceptibility are ill-defined. Knowledge of these molecular mechanisms will inform development of treatment and prevention strategies across comorbid depressive and somatic illnesses. Existing evidence suggests that interleukin-18 (IL-18; an IL-1 family cytokine) is elevated in depression and implicated in pathophysiology underlying comorbid medical illnesses. We previously identified strong associations between baseline IL-18 and μ-opioid receptor availability in major depressive disorder (MDD) volunteers. Combined with the evidence in animal models, we hypothesized that experimental mood induction would change IL-18, the extent proportional to opioid neurotransmitter release. Using the Velten technique in a [11C]carfentanil positron emission tomography neuroimaging study, we examined the impact of experimentally induced mood (sad, neutral) on plasma IL-18 and relationships with concurrent changes in the central opioid neurotransmission in 28 volunteers (healthy, MDD). Results showed mood induction impacted IL-18 (F2,25=12.2, P<0.001), sadness increasing IL-18 (T27=2.6, P=0.01) and neutral mood reducing IL-18 (T27=−4.1, P<0.001). In depressed volunteers, changes in IL-18 were more pronounced (F2,25=3.6, P=0.03) and linearly proportional to sadness-induced μ-opioid activation (left ventral pallidum, bilateral anterior cingulate cortices, right hypothalamus and bilateral amygdala). These data demonstrate that dynamic changes of a pro-inflammatory IL-1 superfamily cytokine, IL-18, and its relationship to μ-opioid neurotransmission in response to experimentally induced sadness. Further testing is warranted to delineate the role of neuroimmune interactions involving IL-18 in enhancing susceptibility to medical illness (that is, diabetes, heart disease and persistent pain states) in depressed individuals.

We discuss the presence of anti-keratin antibodies (AKA) of the IgG class in patients with defined juvenile idiopathic arthritis (JIA). An indirect immunofluorescence test and rat oesophagus substrate was used for the detection and quantification of AKA antibodies in patients´ sera. Overall 33/60 patients with JIA had sera positive for AKA (55 %, P = 0,0001) ranging from 1:10 to 1:160 dilutions. Following idiopathic arthritis of childhood classification criteria AKA occurred in 2/7 patients with systemic disease (28,6 %), in 13/30 patients with RF negative polyarthritis (43,3 %, P = 0,008) and in 15/18 RF positive polyarthritis (83,3 %, P = 0,000002). AKA were also found in a small cohort of patients with oligoarthritis (1/3) and psoriatic arthritis (2/2). AKA positivity occurred in 3/26 healthy controls at a 1:20 dilution. The presence of AKA was correlated as well as with the severity of the disease. Our study revealed that AKA was present overall in 18/29 patients (62%) with severe JIA and in 12/26 patients (46,2 %) with non-severe disease, however this did not reach statistical significance (P = 0,18). We also observed that AKA remained positive regardless of disease activity. AKA were detectable in 55,6 % patients with active JIA and in 48,6 % patients in the complete or near remission. Acknowledgement: This research was supported by a European Commission (Acronym: EUROBANK, contract no: QOL-2000-14.1), web site http://www.ncl.ac.uk and by grant of 2nd Medical Faculty, Charles University in Prague, VZ no. 111300003. P2The significance of antibodies to cyclic citrullinated peptide, antikeratin antibodies, antiperinuclear factor, rheumatoid factor isotypes and HLA shared epitope in prediction of erosive disease in early rheumatoid arthritis patients J Vencovsky, L Sedova, S Machacek, J Gatterova, V Pesakova, J Kafkova and O Krystufkova Institute of Rheumatology, Prague, Czech RepublicObjectives: To evaluate a predictive value of autoantibody examinations in development of erosive disease in early rheumatoid arthritis (RA). Patients and methods: One hundred and fourteen patients with disease duration less than 2 years after the onset of symptoms were investigated. Only patients who fulfilled the diagnostic criteria for RA either at the beginning of the disease or during the follow-up period were included. The antibodies to cyclic citrullinated peptide (anti-CCP) (Immunoscan RA, Euro-diagnostica, The Netherlands), IgM, IgA and IgG rheumatoid factors (RF) were measured by ELISA, antikeratin antibodies (AKA) and antiperinuclear factor (APF) were detected by indirect immunofluorescence, and the presence of HLA shared epitope (HLA SE) was detected by PCR with sequence specific primers. Patients were divided into two groups, either with erosive or non-erosive changes present on the hand or/and feet radiographs at the end of 24 months follow-up. Results: Seventy-six (66.7%) patients developed bony erosion, whereas 38 (33.3%) remained without destructive changes. The initial anti-CCP, AKA, APF, IgM RF, IgA RF, IgG RF ...