Bone Density Status in Bleeding Disorders: Where Are We and What Needs to Be Done?

Bleeding disorders, including hemophilia, can be seen in every ethnic population in the world. Among various bleeding disorders, reduced bone density has been addressed in hemophilia A. In recent years, there has been an increasing interest in addressing osteopenia and osteoporosis in hemophilia A. There is little or no study about the possible susceptibility of other individuals with bleeding disorders to reduced bone density. Questions have been raised about the role of blood coagulation factors in bone mineralization. This review provides new insight and ideas for further survey in the field of bleeding disorders and reduced bone density.

Calcitonin gene-related peptide effects on phenotype and IL-12 production of monocyte-derived dendritic cells in rheumatoid arthritis patients

Recent studies on human indicate that the introduction of therapeutic use of tolerogenic dendritic cell [DC] for chronic inflammatory conditions is imminent. For the purpose of defining CGRP potency in tolerogenic DC production, we investigated the phenotype and IL-12 production of DCs generated from the monocytes of rheumatoid arthritis [RA] patients in the presence of the calcitonin gene-related peptide [CDRP], as a multifunctional neuropeptide. DCs were generated from isolated monocytes from four resistant and two early female RA patients using IL-4, GM-CSF, and CGRP at concentrations of 0, 1, and 100 nM. Then, the phenotype of neuropeptide-treated or untreated DCs was determined using flow cytometry and the IL-12 production was measured by ELISA. Our study showed that, on the last day of the culture, at a concentration of 1 nM CGRP, the mean fluorescence intensity [MFI] for CD80 increased [14.13%] and the MFIs for CD83, CD86, and HLA-DR decreased [14.57%, 5.28%, and 6.88% respectively]. Moreover, at 100 nM CGRP concentration, the MFI for CD80 increased [11.10%] and the MFIs for CD83, CD86, and HLA-DR decreased [4.27%, 18.60%, and 19.75% respectively]. In addition, our results indicated that the mean concentrations of IL-12 produced at 0, 1, and 100 nm CGRP concentrations measured 13.72 +/- 2.41, 11.01 +/- 1.61, and 7 +/- 1.34 pg/ml respectively. Decreased CD83, CD86, and HLA-DR expression and reduced IL-12 production by CGRP were found in the RA patients' monocyte-derived DCs. CD83 is a well-defined DC activation marker. HLA-DR and CD86 are appropriate molecules for inducing an immune response. IL-12 promotes cell-mediated immunity. Therefore we suggest that CGRP may be used as an inducer in the production of tolerogenic DCs

Correlation between serum levels of soluble fas [CD95/Apo-1] with disease activity in systemic lupus erythematosus patients in Khorasan, Iran

Soluble Fas [sFas] is a marker of apoptosis that appears to increase in the serum of systemic lupus erythematosus patients and may have a correlation with disease activity. The exact role of sFas in apoptosis is not clear. The purpose of this study is to assess the correlation between serum levels of soluble Fas [Apo/1-CD95] and the activity of systemic lupus erythematosus. Our study was performed on 114 systemic lupus erythematosus patients who were compared with 50 randomly selected sex, age and race-matched healthy controls. Disease activity was defined according to the Systemic Lupus Erythematosus Disease Activity Index [SLEDAI-2K]. All physical exams and laboratory parameters were collected to determine the SLEDAI. sFas levels were determined using a commercially available ELISA kit. There was a significant difference between serum levels of sFas in the case and control groups [P=0.001]. A significant correlation coefficient existed between the sFas and SLEDAI2K variables [P=0.001, r=0.494]. Significant statistical difference was found between serum levels of sFas in the active and inactive phases of disease according to SLEDAI< 9 or >10, [P=0.002]. The sFas levels were 270 - 300 pg/mL for SLEDAI<9 and 355-502 pg/mL for SLEDAI>10, with a confidence interval of 95%. This study shows a significant elevation of sFas levels in the sera of systemic lupus erythematosus patients with active disease; therefore it can be used as an appropriate marker for evaluation of disease activity

Association of HLA-DQB1 allelic sequence variation with susceptibility to systemic lupus erythematosus

Systemic lupus erythematosus [SLE] is an autoimmune disease in which polymorphisms within the human leukocyte antigen [HLA] region have been associated to its etiology. We conducted this study to compare the HLA-DQB1 allelic sequence variation among SLE patients and controls in the northeast of Iran. Genomic DNA of 40 SLE patients and 83 healthy controls were amplified by Polymerase Chain Reaction with Sequence-Specific Primers technique [PCR-SSP]. Seven serological subclasses of the HLA DQB1 were detected. Allele distribution comparison showed in the SLE group a significant increase of HLA DQ6 [*0601-*0609] [p=0.006]; whereas alleles HLA DQ7 [*0301-*0304] were significantly decreased [p=0.005]. Combination of DQ5 [*0501-*0504]-DQ6 [*0601-*0609] was increased in patients. These results suggest that DQ6 is the dominant HLA DQB1 allele probably associated with genetic susceptibility to SLE in the northeast of Iran. The association supports the importance of ethnic background and indicates the importance of various genes that has been observed in different SLE populations