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Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is a newly assigned member of the Ig immunoreceptor tyrosine-based inhibitory motif superfamily, and its functional role is suggested to be an inhibitory receptor that modulates immunoreceptor tyrosine-based activation motif-dependent signaling cascades. To test whether PECAM-1 is capable of delivering inhibitory signals in B cells and the functional requirement of protein-tyrosine phosphatases (PTPs) for this inhibitory signaling, we generated chimeric FcγRIIB1-PECAM-1 receptors containing the extracellular and transmembrane portions of murine FcγRIIB1 and the cytoplasmic domain of human PECAM-1. These chimeric receptors were stably expressed in chicken DT40 B cells either as wild-type or mutant cells deficient in SHP-1−/−, SHP-2−/−, SHIP−/−, or SHP-1/2−/− and then assessed for their ability to inhibit B cell Ag receptor (BCR) signaling. Coligation of wild-type FcγRIIB1-PECAM-1 with BCR resulted in inhibition of intracellular calcium release, suggesting that the cytoplasmic domain of PECAM-1 is capable of delivering an inhibitory signal that blocks BCR-mediated activation. This PECAM-1-mediated inhibitory signaling correlated with tyrosine phosphorylation of the FcγRIIB1-PECAM-1 chimera, recruitment of SHP-1 and SHP-2 PTPs by the phosphorylated chimera, and attenuation of calcium mobilization responses. Mutational analysis of the two tyrosine residues, 663 and 686, constituting the immunoreceptor tyrosine-based inhibitory motifs in PECAM-1 revealed that both tyrosine residues play a crucial role in the inhibitory signal. Functional analysis of various PTP-deficient DT40 B cell lines stably expressing wild-type chimeric FcγRIIB1-PECAM-1 receptor indicated that cytoplasmic Src homology 2-domain-containing phosphatases, SHP-1 and SHP-2, were both necessary and sufficient to deliver inhibitory negative regulation upon coligation of BCR complex with inhibitory receptor.

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The frequency distribution of HLA antigens was studied in a group of psoriatic patients with and withoqt arthritis. HLA-BW38 was found significantly increased in the group with peripheral psoriatic arthritis. There were no differences in the clinical features of the arthritis in the BW38 positive (+) and BW38 negative ( -) individuals. It is suggested that BW38 is a genetic marker and/or an indicator of peripheral joint involvement in psoriatic patients.A clear correlation between HLA-B13 and HLA-BW17 and psoriasis has been established in several white populations (1-3). A statistically significant association has also been reported between HLA-B27 and the axial (spondylitic) type of arthritis often seen in psoriatic patients (43). There has been, however, considerable debate about HLA antigens and the peripheral type of psoriatic arthritis. A number of associations have been reported (4,6,7). However, other workers have been unable to confirm these observations (8-10).In this study, which was aimed at defining the association between HLA and peripheral psoriatic arthritis, findings indicate a significantly increased frequency of HLA-BW38. This phenotype was not increased in a group of psoriatic patients in whom arthritis was not present. HLA-B27 was not increased in the peripheral arthritis group, but it was present in the majority of patients with spinal involvement. PATIENTS AND METHODSA total of 60 unrelated, white psoriatic patients from the Montreal area were studied. These included 32 with psoriasis alone and 28 with psoriasis and arthritis. Patients studied were either attending the Rheumatic Disease Unit (RDU) or being treated in the dermatology ward of the Royal Victoria Hospital for extensive skin involvement. The following clinical features were evaluated: age of onset, extent and severity of disease, initiating factors, distribution of skin or joint involvement, and family history. The diagnosis of psoriasis was confirmed by the dermatology department in all cases. The Moll and Wright (11) criteria for the diagnosis of psoriatic arthritis was used. All patients with psoriatic arthritis had negative rheumatoid factor. Radiographs of involved peripheral joints, sacroiliac (SI) joints, and spine were available in all patients with psoriatic arthritis. In the group of patients with psoriasis but without arthritis, radiographs were taken to rule out the presence of arthritis involvement only when there was the slight suspicion that joint involvement might be present.The presence of spondylitis and/or sacroiliitis was determined by using McEwen (12) and the Rome criteria (13). Rheumatoid factor was detected by latex fixation.