Significance of microparticles in progressive systemic sclerosis with interstitial pneumonia.

We measured and compared the levels of microparticles, chemokines, cell adhesion molecules and platelet activation markers with a view to developing a better understanding of their potential contributions to the pathophysiology of progressive systemic sclerosis (PSS, scleroderma). The concentrations of all the factors in PSS patients were significantly higher than those in normal subjects. PSS patients were divided to two groups by whether they have interstitial pneumonia (IP) or not. There were no differences in the levels of soluble(s) VCAM-1, sICAM-1, sE-selectin and IL-8 between the two groups. However, there were significant between-group differences in the levels of sP-selectin, sCD40L, ENA-78, RANTES (regulated on activation normally T-cell expressed and secreted), platelet-derived microparticles (PDMPs), monocyte-derived microparticle (MDMPs) and KL-6. The level of tissue factor expression on monocytes by A23187 stimulation in PSS patients was found to be similar to that in healthy controls. Although PDMP did not induce the expression of tissue factor on monocytic cell line (THP-1) directly, the recombinant sCD40 ligand-induced expression of tissue factor on THP-1 and generation of MDMP from this cell line were enhanced by the addition of PDMPs. Our findings suggested that elevated levels of PDMPs and MDMPs may be interpreted as a sign of vascular complications in PSS patients, particularly those complicated with IP, offering a new treatment strategy in these patients.

Significance of anti-oxidized LDL antibody and monocyte-derived microparticles in anti-phospholipid antibody syndrome.

Monocytes, platelets, endothelial cells and oxidized LDL could be very important in development of vascular complication in thrombotic diseases. We measured and compared the levels of plasma monocyte-derived microparticles (MDMPs), platelet-derived microparticles (PDMPs), and anti-oxidized LDL antibody, to develop a better understanding of their potential contribution to vascular complications in antiphospholipid antibody syndrome (APS). The concentration of MDMP in APS patients was significantly higher (p < 0.01) than that in normal subjects and SLE patients. When levels of PDMPs and plt-P-selectin were compared between the control and APS patients, levels of PDMPs and plt-P-selectin were significantly higher (p < 0.01 for each) in APS patients than in controls. In addition, these levels of platelet activation markers correlated with MDMP in APS patients. Twenty one of the 37 APS patients (56.8%) had elevated levels of anti-oxLDL antibody. In addition, a significant increase in MDMP was observed in anti-oxLDL antibody-positive APS patients (p < 0.01). These findings suggest that elevated MDMPs may be a sign of vascular complication in APS patients, particularly those who are detected anti-oxLDL antibodies.

Human leukocyte antigen haplotype and autoantibodies of a family with systemic lupus erythematosus.

A search for HLA haplotypes of a family of five indicated that four members had the same haplotype. Systemic lupus erythematosus (SLE) had already developed in three of these four people. SLE has now developed in the remaining person, and the result is that all the members of the family having the same haplotype will develop SLE. Regarding these four SLE patients, the types of autoantibodies and the symptoms were different in each person, so the idea that this haplotype is strongly related to the onset of SLE but minimally related to the symptoms was suggested.

Significance of chemokines and soluble CD40 ligand in patients with autoimmune thrombocytopenic purpura.

We investigated the levels of various chemokines and soluble CD40L (sCD40L) in ITP patients, in order to determine the influence of CD40-CD40L interaction on the pathogenesis of ITP. We found increases in MCP-1 and RANTES levels in ITP patients compared with those in healthy individuals. Thirty-eight of the 65 ITP patients (58.5%) had elevated levels of sCD40L. We found significant decreases in platelet counts in sCD40L-positive ITP patients. Although the sCD40L level did not differ significantly between the control and nonimmune thrombocytopenia groups, but among ITP patients. sCD40L level was significantly higher in those with untreated ITP than in those with treated ITP. In addition, significant increases in RANTES, MCP-1, sCD14, and sP-selectin levels were observed in sCD40L-positive ITP patients, although sE-selectin levels were not increased in such patients. For other factors examined, however, there were no differences in level between sCD40L-positive and -negative ITP patients. These findings suggests that there are two groups of ITP patients, one with elevated and one with normal of sCD40L. ITP cases in which sCD40L was increased appeared to involve changes in platelet counts and monocyte activation. The pathogenesis of ITP may in some patients include alterations of the CD40/CD40L pathway.