Subject(s)
Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/genetics , Isoxazoles/adverse effects , Oxidoreductases Acting on CH-CH Group Donors/genetics , Aged , Arthritis, Rheumatoid/drug therapy , Cytochrome P-450 CYP1A2/genetics , Dihydroorotate Dehydrogenase , Female , Humans , Leflunomide , Male , Middle Aged , Polymorphism, GeneticABSTRACT
OBJECTIVES: Glutathione S-transferases (GST); GST-mu1 (GSTM1), GST-pi1 (GSTP1) and GST-theta1 (GSTT1) have peroxidase activity towards cytotoxic metabolites produced in inflammatory reactions, the main feature of rheumatoid arthritis (RA). Genetic polymorphisms in GSTM1, GSTP1 and GSTT1 modify the enzyme conjugation capacity and may be associated with the activity of RA. METHODS: A genotyping approach was used to analyze GSTM1-0, GSTT1-0 and GSTP1 Ile105Val and Ala114Val polymorphisms in 213 RA patients. Disease activity was assessed by the disease activity score of 28 joint counts (DAS28) twice for each patient and mean DAS28 values were calculated. RESULTS: The patients with GSTT1-0 genotype had a higher risk for developing high activity RA than the patients with GSTT1 genes present (p=0.028, OR=2.761, 95% CI=1.114-6.843). An interaction between the GSTT1 polymorphism and smoking was observed. In the group of smokers, the carriers of a homozygous deletion GSTT1 had an 8.5-fold higher risk for developing high disease activity than the patients with the GSTT1-1 genotype (p=0.004, OR=8.640, 95% CI=1.995-37.426). GSTM1 and GSTP1 polymorphisms were not associated with the disease activity. CONCLUSION: Our results suggest that the presence of the GSTT1-0 genotype contributed to higher disease activity in RA patients. The risk for developing highly active RA was the highest in smokers with the GSTT1-0 genotype.
Subject(s)
Arthritis, Rheumatoid/genetics , Glutathione Transferase/genetics , Polymorphism, Single Nucleotide , Smoking/genetics , Aged , Female , Genotype , Glutathione S-Transferase pi/genetics , Humans , Male , Middle Aged , Severity of Illness Index , Smoking/adverse effectsSubject(s)
Complement Inactivator Proteins , Graft Rejection , Pregnancy Proteins/isolation & purification , Pregnancy-Associated Plasma Protein-A/isolation & purification , alpha-Macroglobulins/isolation & purification , Animals , Cells, Cultured , Female , Humans , Male , Pregnancy , Pregnancy-Associated Plasma Protein-A/immunology , Rats , Rats, Inbred F344 , Rats, Inbred WF , Skin Transplantation , Transplantation, Homologous , Urodela , alpha-Macroglobulins/immunologyABSTRACT
This work report the partial purification of an alpha 2-macroglobulin present in the serum of allopregnant rats. Ultrogel filtration followed by immune absorption on different antisera were used giving a single band on polyacrylamide gel electrophoresis. This fraction was able to inhibit in vitro T cell cytotoxic response to allogenic cells. When administered repeatedly to rats it significantly increased the survival of skin allograft. This alpha 2-macroglobulin fraction isolated from allopregnant rats was denominated IRG to its graft rejection inhibitory activity.
Subject(s)
Graft Enhancement, Immunologic , Pregnancy Proteins/immunology , Skin Transplantation , Animals , Female , Immune Tolerance , Male , Pregnancy , Pregnancy Proteins/isolation & purification , Rats , Rats, Inbred Strains , T-Lymphocytes, Cytotoxic/immunology , Time FactorsABSTRACT
In this article Pierre Grabar returns to the proposal he first made 30 years ago that alloreactive and autoreactive antibodies represent a physiological system for disposing of the products of metabolism and catabolism.
ABSTRACT
The injection of free non-reactive hapten, before immunization with the same hapten conjugated to one carrier protein, induces specific unresponsiveness to the hapten in Rats. Two haptens have been assayed: dinitrophenyl-Lysine and Arsonate-Tyrosine. In both cases, the Rats responded normally to the carrier but did not respond to the hapten. These results can be explained by assuming that the hapten blocks the specific receptors of the immunocompetent cells.
Subject(s)
Haptens , Immune Tolerance , Animals , Antibody Formation , Antigens/administration & dosage , Arsenicals , Haptens/administration & dosage , Hemagglutination Tests , Lysine/analogs & derivatives , Nitrobenzenes , Rats , Tyrosine/analogs & derivativesSubject(s)
Immunity , Immunoglobulins/metabolism , Antibody Formation , Autoantibodies , Humans , Immune ToleranceSubject(s)
Antigens/analysis , Immunochemistry/methods , Absorption , Antibody Formation , Antilymphocyte Serum , Centrifugation, Density Gradient , Enzymes , Fluorescent Antibody Technique , Hemagglutination Tests , Immune Sera , Immunodiffusion , Immunoelectrophoresis , Isoelectric Focusing , Molecular Conformation , Radioisotopes , Subcellular Fractions , Tannins , Tissue ExtractsABSTRACT
A hypothesis is put forward to the effect that immunological phenomena represent a particular case of the transport of metabolites, rather than obligatory "defense mechanism". This hypothesis excludes the necessity in additional postulates (forbidden clones, somatic mutations, cells-repressors etc.) to account for the basic immunological phenomena, such as recognition, appearance of autoantibodies and tolerance. It suffices to assume that: 1) autolytic enzymes destroy "their" antigens but cannot destroy completely "foreign" antigens; 2) as a result of decomposition of antigens by enzymes, "tolerogens" may appear which block the receptors in immunocompetent cells thus preventing the appearance of antibodies; 3) cells capable to synthesize autoantibodies exist in the normal organism but not activated due to the absence of "their" antigens. When such antigens appear, they initiate the synthesis of antibodies. The hypothesis advanced may appear too simple as compared with the existing theories, but experiments have to confirm it.
