Fifteen sibships, each having two or more siblings affected by classical or definite RA were studied. They comprised 31 patients with RA (all in remission) and 21 normal siblings. The total severity index of RA was assessed by clinical and radiological indices. For all the patients the following investigations were carried out: (1) HLA antigens determination for nine antigens at A locus and 15 ...

Two human T-lymphocyte clones, derived from a mixed leukocyte culture (MLC) with stimulating cells from a type I diabetic patient, define a subset of HLA-DR4, tentatively called "DR4S." In testing of 69 random type I diabetic subjects and 69 random controls, 79% (37/47) of DR4-positive patients, but only 44% (8/18) of DR4-positive controls, had DR4S (P less than 0.01). The relative risk of type...

OBJECTIVES Previous reports have shown that HLA-DR4 may be a severity marker for rheumatoid arthritis (RA) in patients of northern European origin. The aim of the present study was to investigate this relation in Greek patients with RA, as RA in Greece differs from the RA described previously on clinical, serological, and immunological grounds. METHODS Eighty four patients were studied in who...

Death receptor 4 (DR4) is a cell surface receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and triggers apoptosis upon ligation with TRAIL or aggregation. MEK/ERK signaling is a well known and the best-studied effector pathway downstream of Ras and Raf. This study focuses on determining the impact of pharmacological MEK inhibition on DR4 expression and elucidating the...

Stimulation of the proapoptotic tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptors, death receptors 4 (DR4) and 5 (DR5), conventionally induces caspase-dependent apoptosis in tumor cells. Here we report that stimulation of DR4 and/or DR5 by the agonistic protein KD548-Fc, an Fc-fused DR4/DR5 dual-specific Kringle domain variant, activates plasma membrane-associated ...

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) mediates apoptosis in cancer cells through death receptors DR4 and DR5 preferring often one receptor over another in the cells expressing both receptors. Receptor selective mutant variants of TRAIL and agonistic antibodies against DR4 and DR5 are highly promising anticancer agents. Here using DR5 specific mutant variant of TRAIL--D...

BACKGROUND TNF-related apoptosis-inducing ligand/Apo2 ligand (TRAIL/Apo2L) selectively induces apoptosis in various cancer cells including myeloma (MM) cells. However, the susceptibility of MM cells to TRAIL is largely low in most of MM cells by yet largely unknown mechanisms. Because TNF-α converting enzyme (TACE) can cleave some TNF receptor family members, in the present study we explored th...

DQ beta and C4 null alleles have been defined in patients with rheumatoid arthritis, Felty's syndrome, and in control subjects. Comparison of DR4 positive subjects shows that rheumatoid disease without extra-articular features has no preferential associations with either DQ beta or C4 null variants. In Felty's syndrome there are significant associations with both the class II major histocompati...

One hundred and forty-two patients with 'definite' or 'classical' rheumatoid arthritis (RA) were studied for the frequency and possible prognostic significance of HLA DR4. Of these, 122 were seropositive, while 20 were negative for rheumatoid factor (RF) in serum. The HLA antigen DR4 was significantly increased in the seropositive group (65%) as well as in the seronegative group (55%) in compar...

MHC class II molecules are critical determinants of genetic susceptibility to human type 1 diabetes. In patients, the most common haplotype contains the DRA1*0101-DRB1*0401 (DR4) and DQA1*0301-DQB1*0302 (DQ8) loci. To assess directly the relative roles of HLA-DQ8 and DR4 for diabetes development in vivo, we generated C57BL/6 transgenic mice that lack endogenous mouse MHC class II molecules but ...