Biomedical subjects

M Breban

Publications and source records attributed to M Breban.

44 records · Page 3Linked to original sources

PubMed1993

Transfer of the inflammatory disease of HLA-B27 transgenic rats by bone marrow engraftment.

We have previously produced lines of rats transgenic for HLA-B27 and human beta 2-microglobulin (h beta 2m) that develop a progressive inflammatory disease sharing many clinical and histologic features with the B27-associated human spondyloarthropathies, including gut and male genital inflammation, arthritis, and psoriasiform skin lesions. Other transgenic lines that express lower levels of B27 and h beta 2m remain healthy. To investigate the cellular basis for the multisystem inflammatory disease in these rats, we transferred lymphoid cell populations from disease-prone transgenic lines to irradiated disease-resistant transgenic and nontransgenic recipients. In recipients of cells from two different disease-prone lines, successful transfer required engraftment of bone marrow cells. Transfer of disease with fetal liver cells suggested that neither mature effector cells nor active disease in the donors was necessary for induction of disease in the recipients. Remission of the spontaneous disease in irradiated transgenic rats was induced by engraftment of nontransgenic bone marrow. These results suggest that the expression of HLA-B27 in bone marrow-derived cells alone is sufficient for the development of B27-associated disease, and that disease transfer requires engraftment of a bone marrow precursor cell for which mature cells in spleen or in lymph node cannot substitute.

Animals↗

PubMed1993

Susceptibility to inflammatory disease in HLA-B27 transgenic rat lines correlates with the level of B27 expression.

To investigate the role of the class I MHC molecule HLA-B27 in the spondyloarthropathies, we produced rats transgenic for HLA-B27 and human beta 2-microglobulin. Of five lines bearing > 1 copy of each transgene and showing hemizygous expression of both transgenes, two (lines 21-4H and 33-3) developed spontaneous inflammatory disease that closely resembled B27-associated human disease. Two lines, 21-4L and 25-6, remained healthy even when homozygous for the transgene locus, whereas the 21-3 line, bearing the third highest transgene copy number, developed disease similar to that of the 21-4H and 33-3 lines only when homozygous for the transgene locus. The disease-prone lines showed higher expression of B27--thymic mRNA in utero, splenic mRNA by 5 days of age, and splenic cell surface protein by the time of disease onset--than the disease-resistant lines. Disease susceptibility thus appeared to correlate with gene copy number and the quantity of B27 in lymphoid cells. The increase in the amount of B27 protein did not appear to be simply a consequence of the inflammatory disease because 1) there was no similar change in endogenous RT1 class I expression; 2) no alteration of B27 expression occurred in 21-4H rats with adjuvant-induced arthritis; 3) in rats with inflammatory disease transgenic for HLA-A2 and the 21-4H transgene locus, A2 expression was the same as in healthy rats transgenic for A2 but not B27; and 4) the transgenes in disease-prone and disease-resistant lines were equally susceptible to induction by IFN-gamma. Immunocytochemistry of the distal colon, an early site of inflammation, showed that the B27 Ag is expressed at high levels in cells of the lamina propria, but not at all in colonic epithelial cells. Taken together, the data suggest that the B27 transgene is expressed in a copy number dependent, position-independent manner in lymphoid tissue and that disease results from the expression of B27 above a critical threshold level.

Animals↗

PubMed1993

Sharing of an HLA-B27-restricted H-Y antigen between rat and mouse.

The purpose of this work was twofold: 1) to learn whether rats transgenic for HLA-B27 and the human beta 2-microglobulin gene HB2M can mount B27-restricted cytolytic T lymphocyte (CTL) responses to the male H-Y antigen, and 2) to learn whether such CTLs would recognize both rat and mouse H-Y in the context of HLA-B27. Female rats of the B27/HB2M transgenic line 21-4L were primed in vivo with cells from males of the same line. CTL effectors were generated from lymph node cells of these females following culture with irradiated antigen-presenting cells from either male 21-4L rats or male mice of the B27/HB2M transgenic 56-3 line. The CTLs showed male-specific, B27-specific lysis of both rat and mouse targets. Lysis of B27 targets was inhibitable by monoclonal antibodies specific for B27 or rat CD8. Specific lysis of male B27 rat and mouse targets was inhibitable equally by either rat or mouse male B27 cold targets, but not significantly by female or nontransgenic cold targets. The B27-restricted CTLs neither recognized nor were inhibited by B27+ or B27- male or female human targets. These results demonstrate that CD8+, B27-restricted, anti-H-Y CTLs recognize an evolutionarily conserved H-Y peptide antigen in both rats and mice. In addition, they establish the transgenic rat as a model system for examining the T-cell response to antigen presented by class I HLA molecules.

Animals↗

PubMed1992

Protective effects of ciprofloxacin against type II collagen induced arthritis in rats.

Ciprofloxacin, a new fluoroquinolone antibiotic, inhibits the in vitro production of interleukin 1 beta and tumor necrosis factor alpha by monocytes. We investigated its activity against type II collagen induced arthritis in rats. It exerted a dose dependent preventive effect at 50 and 75 mg/kg/day against clinical and histologic features of collagen induced arthritis without any influence on the production of anticollagen antibodies and alpha 1-acid glycoprotein. This effect was reversible after early removal of the treatment. Ciprofloxacin did not inhibit collagen induced arthritis in adrenalectomized rats but rather caused an exacerbation of the disease. Its effect was not modified by the simultaneous administration of an antiglucocorticoid, RU 40555.

Adrenal Cortex Hormones↗

PubMed1991

The actual survival rate in systemic lupus erythematosus: study of a 1976 cohort.

The purpose of this study was to establish the actual survival rate of a cohort of 51 patients with systemic lupus erythematosus (SLE) all of whom were followed during 12 years from 1976 to 1988 and to evaluate the prognostic significance of the severe complications of the disease. Forty-eight were females. The mean age was 28.5 at onset, 36.2 at diagnosis and 42 at entry; 80% had four or more 1982 ARA criteria at diagnosis and 96% in 1988. Survival rates were: 96% at two years, 86.3% at five years and 74.5% at twelve years. The main cause of death was infection (62%); SLE was directly responsible in only one case. Manifestations considered as severe occurred in almost two-thirds of the cases without any concordance in the time sufficient to recognize different severe forms of the disease.

Adolescent↗

PubMedDate not supplied

Treatment of the SpA-like disease in HLA B27 transgenic animals.

A major involvement of the immune system and of microbial flora in the HLA-B27 transgenic rat model of spondylarthropathy was demonstrated. The role of inflammatory pathways, such as cytokines and inducible nitric oxide synthase (iNOS) was investigated. Treatment with IL-10 failed to improve established disease, whereas such improvement was achieved with IL-11. In contrast, aggravation was observed after treatment with selective inhibitor of iNOS.

Animals↗

PubMedDate not supplied

Thalidomide in ankylosing spondylitis.

Despite potential side effects dominated by teratogenicity and peripheral neuropathy, thalidomide has recently been used to treat severe ankylosing spondylitis (AS). Over 50 patients have been treated across several 6-12 month open studies. Altogether 68% of the patients improved and the drop-out rate was 19%. Inhibition of NF-kappaB and/or TNFalpha is a putative mechanism for thalidomide efficacy in AS.

Clinical Trials as Topic↗

PubMedDate not supplied

Infliximab in spondylarthropathy--influence on bone density.

Osteoporosis is frequently associated with Ankylosing Spondylitis (AS). Bone mineral density (BMD) decreased predominantly in patients with active disease. Moreover, conventional therapy, i.e. NSAID seems to have no influence in the bone loss. It has been suggested that local or systemic inflammatory cytokine release might be implicated in bone loss. Monoclonal antibody to TNFalpha in patients with AS demonstrated significant clinical response with significant reduction in the acute-phase reactants ESR and CRP. We evaluated the changes in bone mineral density (BMD) in patients with Spondylarthropathy (SpA) treated with infliximab (a human/mouse neutralising chimeric monoclonal antibody). We included 29 patients. In 6 months, there was a statistically significant increase in BMD both at the spine and total hip. There was an increase in osteocalcin between baseline and week 6. These data suggest a benefit of anti-TNFalpha therapy on BMD in patients with SpA, may be through an uncoupling effect on bone cells.

Adult↗