mercaptopurine and Autoimmune-Diseases

There is an evolving understanding that autoimmune pancreatitis (AIP) is an immunoglobulin (Ig) G4 systemic disease. It can manifest as primarily a pancreatic disorder or in association with other disorders of presumed autoimmune cause. Classic clinical characteristics include obstructive jaundice, abdominal pain, and acute pancreatitis. Thus, AIP can be difficult to distinguish from pancreatic malignancy. However, AIP may respond to therapy with corticosteroids, and has a strong association with other immune mediated diseases. Although primarily a pathologic diagnosis, attempts have been made to reliably diagnose AIP clinically. AIP can be classified as either type 1 or type 2.

Topics: Adrenal Cortex Hormones; Autoimmune Diseases; Azathioprine; Biopsy; Cholangiopancreatography, Endoscopic Retrograde; Cyclophosphamide; Cyclosporine; Disease Management; Endosonography; Humans; Immunoglobulin G; Immunologic Factors; Immunosuppressive Agents; Mercaptopurine; Pancreas; Pancreatitis; Rituximab; Tomography, X-Ray Computed

The treatment of auto-immune diseases is evolving and newer agents become available. This review will outline treatment options in children with auto-immune disorders. Treatment with current corticosteroids and azathioprine works in majority but issues of intolerance and incomplete response arise, which led to window of newer immunosuppressants including mycophenolate mofetil, cyclosporine, tacrolimus, sirolimus, and various antibodies of human and animal origin. The newer agents have been studied in fewer numbers of children, so they are not first-line treatment yet but do have a clear role in patients with intolerance or incomplete response to standard therapy.

Topics: Antilymphocyte Serum; Autoimmune Diseases; Azathioprine; Child; Cyclophosphamide; Cyclosporine; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Isoxazoles; Leflunomide; Mercaptopurine; Methotrexate; Mycophenolic Acid; Nitriles; Sirolimus; Tacrolimus

To examine whether pretreatment determination of thiopurine methyltransferase (TPMT) enzymatic activity (phenotyping) or TPMT genotype, to guide thiopurine therapy in chronic autoimmune disease patients, reduces treatment harms. Other objectives included assessing: preanalytic, analytic, and postanalytic requirements for TPMT testing; diagnostic accuracy of TPMT genotyping versus phenotyping; association of thiopurine toxicity with TPMT genotypic or phenotypic status; and costs of testing, care, and treating drug-associated complications.. MEDLINE®, EMBASE®, and Healthstar were searched from inception to May 2010; the Cochrane Library® to October 2009; and BIOSIS®, Genetics Abstracts, and EconLit™ to May 2009, for English language records.. A reviewer screened records, and a second reviewer verified exclusions and subsequent selection of relevant studies. Studies in patients with leukemia and organ transplant were excluded. Additionally, laboratories that provide TPMT analytical services were surveyed to assess means of TPMT testing in practice. Where possible, risk of bias was assessed using standard criteria. Meta-analyses estimated diagnostic sensitivity, and specificity; and odds ratios of associations.. 1790 titles or abstracts, and 538 full text records were screened. 114 observational studies and one RCT were included. Majority of studies were rated fair quality, except for diagnostic studies with 37 percent of studies rated poor. In general, there were few patients who were homozygous (or compound heterozygous) for TPMT variant alleles in the included studies limiting applicability. There is insufficient evidence examining effectiveness of pretesting in terms of reduction in clinical adverse events. Sufficient preanalytical data were available regarding preferred specimen collection, stability and storage conditions for TPMT testing. There was no clinically significant effect of age, gender, various coadministered drugs, or most morbidities (with the exception of renal failure and dialysis). TPMT phenotyping methods had coefficients of variation generally below 10 percent. TPMT genotyping reproducibility is generally between 95-100 percent. The sensitivity of genotyping to identify patients with low or intermediate TPMT enzymatic activity is imprecise, ranging from 70.70 to 82.10 percent (95 percent CI, lower bound range 37.90 to 54.00 percent; upper bound range 84.60 to 96.90 percent). Sensitivity of homozygous TPMT genotype to correctly identify patients with low to absent enzymatic activity was 87.10 percent (95 percent CI 44.30 to 98.30 percent). Genotyping specificity approached 100 percent. Leukopenia was significantly associated with low and intermediate enzymatic activity (low activity OR 80.00, 95 percent CI 11.5 to 559; and intermediate activity OR 2.96, 95 percent CI 1.18 to 7.42), and homozygous and heterozygous TPMT variant allele genotype (OR 18.60, 95 percent CI 4.12 to 83.60; and 4.62, 95 percent CI 2.34 to 9.16, respectively). In general, TPMT phenotyping costs less than genotyping, although estimates across studies are quite heterogeneous.. There is insufficient direct evidence regarding the effectiveness of pretesting of TPMT status in patients with chronic autoimmune diseases. Indirect evidence confirms strong association of leukopenia with lower levels of TPMT activity and carrier genotype already established in the literature.

Topics: Autoimmune Diseases; Chronic Disease; Female; Humans; Leukopenia; Male; Mercaptopurine; Methyltransferases; Reproducibility of Results

Topics: Autoimmune Diseases; Azathioprine; Genotype; Humans; Immunosuppressive Agents; Mercaptopurine; Methyltransferases; Phenotype

Topics: Animals; Antibodies; Antibodies, Monoclonal; Autoantigens; Autoimmune Diseases; B-Lymphocytes; Cells, Cultured; DNA; Epitopes; Female; Haptens; Humans; Immune Tolerance; Immunoglobulin G; Immunosuppression Therapy; Immunosuppressive Agents; Immunotherapy; Lupus Erythematosus, Systemic; Male; Mercaptopurine; Mice; Nucleosides; T-Lymphocytes

Topics: Acquired Immunodeficiency Syndrome; Animals; Antibody Formation; Autoimmune Diseases; Cyclophosphamide; Herpesviridae Infections; Humans; Immunization, Passive; Immunoglobulin Idiotypes; Immunosuppression Therapy; Immunosuppressive Agents; Leukemia; Lymphoma; Mercaptopurine; Sarcoma, Kaposi; T-Lymphocytes; Transplantation Immunology

Topics: Adolescent; Adrenal Cortex Hormones; Alkylating Agents; Anemia; Anemia, Aplastic; Anemia, Hemolytic, Autoimmune; Antilymphocyte Serum; Arthritis, Rheumatoid; Autoimmune Diseases; Azathioprine; Colchicine; Cyclosporins; Danazol; Female; Hepatitis, Chronic; Humans; Immunoglobulin G; Immunosuppressive Agents; Levamisole; Lupus Erythematosus, Systemic; Male; Mercaptopurine; Methotrexate; Multiple Sclerosis; Pregnancy

Topics: Autoimmune Diseases; Azathioprine; Cyclophosphamide; DNA; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Mercaptopurine; T-Lymphocytes

Topics: Alcoholism; Animals; Antigens; Autoantigens; Autoimmune Diseases; Cell Migration Inhibition; Hepatitis; Humans; Immunity, Cellular; Leukocytes; Liver; Macrophage Migration-Inhibitory Factors; Mercaptopurine

Topics: Adrenal Cortex Hormones; Autoimmune Diseases; Azathioprine; Chlorambucil; Cyclophosphamide; Drug Therapy, Combination; Folic Acid Antagonists; Histamine H1 Antagonists; Humans; Immunosuppression Therapy; Mercaptopurine; Salicylates; Skin; Skin Diseases

Topics: Adrenocorticotropic Hormone; Adult; Autoimmune Diseases; Azathioprine; Blood Platelets; Blood Transfusion; Cell Survival; Child; Cyclophosphamide; Female; Humans; Infant, Newborn; Kinetics; Male; Mercaptopurine; Prednisone; Pregnancy; Purpura, Thrombocytopenic; Splenectomy; Thioguanine

Topics: Adrenocorticotropic Hormone; Aminopterin; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Autoimmune Diseases; Azathioprine; Chlorambucil; Clinical Trials as Topic; Cyclophosphamide; Humans; Immunosuppressive Agents; Mercaptopurine; Methotrexate; Nitrogen Mustard Compounds; Penicillamine

Topics: Adrenal Cortex Hormones; Animals; Antibody Formation; Autoimmune Diseases; Azathioprine; Cyclophosphamide; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mercaptopurine; Methotrexate; Pemphigus; Skin Diseases

Topics: Antigen-Antibody Reactions; Antilymphocyte Serum; Autoimmune Diseases; Azathioprine; Cyclophosphamide; Dactinomycin; Humans; Immunosuppressive Agents; Mercaptopurine; Methotrexate; Steroids; Transplantation Immunology

Topics: Adrenal Cortex Hormones; Adult; Allopurinol; Autoimmune Diseases; Azathioprine; Bone Diseases; Diabetes Mellitus; Drug Synergism; Duodenal Ulcer; Embolism, Fat; Glomerulonephritis; Histocompatibility; Humans; Hypertension, Renal; Immunosuppressive Agents; Infections; Kidney Glomerulus; Kidney Transplantation; Malabsorption Syndromes; Male; Mercaptopurine; Neoplasm Transplantation; Neoplasms; Obesity; Osteoporosis; Pancreatitis; Peptic Ulcer Hemorrhage; Phenylbutazone; Postoperative Complications; Proteinuria; Transplantation, Homologous

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Anemia; Anemia, Hemolytic; Antibody Formation; Antigens; Autoimmune Diseases; Autoimmunity; gamma-Globulins; Haptoglobins; Immune Tolerance; Mechlorethamine; Mercaptopurine; Quinidine; Research; Splenectomy; Thymus Gland; Toxicology; Transplantation Immunology

Topics: Adrenocorticotropic Hormone; Aminopterin; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Autoimmune Diseases; Azathioprine; Chlorambucil; Clinical Trials as Topic; Cyclophosphamide; Humans; Immunosuppressive Agents; Mercaptopurine; Methotrexate; Nitrogen Mustard Compounds; Penicillamine

The aim of this study was to describe the long-term health outcomes of children born to mothers with inflammatory bowel disease (IBD) and to assess the impact of maternal IBD medication use on these outcomes.. We performed a multicentre retrospective study in The Netherlands. Women with IBD who gave birth between 1999 and 2018 were enrolled from 20 participating hospitals. Information regarding disease characteristics, medication use, lifestyle, pregnancy outcomes and long-term health outcomes of children was retrieved from mothers and medical charts. After consent of both parents, outcomes until 5 years were also collected from general practitioners. Our primary aim was to assess infection rate and our secondary aims were to assess adverse reactions to vaccinations, growth, autoimmune diseases and malignancies.. We included 1000 children born to 626 mothers (381 (61%) Crohn's disease, 225 (36%) ulcerative colitis and 20 (3%) IBD unclassified). In total, 196 (20%) had intrauterine exposure to anti-tumour necrosis factor-α (anti-TNF-α) (60 with concomitant thiopurine) and 240 (24%) were exposed to thiopurine monotherapy. The 564 children (56%) not exposed to anti-TNF-α and/or thiopurine served as control group. There was no association between adverse long-term health outcomes and in utero exposure to IBD treatment. We did find an increased rate of intrahepatic cholestasis of pregnancy (ICP) in case thiopurine was used during the pregnancy without affecting birth outcomes and long-term health outcomes of children. All outcomes correspond with the general age-adjusted population.. In our study, we found no association between in utero exposure to anti-TNF-α and/or thiopurine and the long-term outcomes antibiotic-treated infections, severe infections needing hospital admission, adverse reactions to vaccinations, growth failure, autoimmune diseases and malignancies.

Topics: Adalimumab; Adult; Anti-Bacterial Agents; Autoimmune Diseases; Cesarean Section; Child Development; Child, Preschool; Congenital Abnormalities; Drug Prescriptions; Drug Therapy, Combination; Female; Gastrointestinal Agents; Humans; Infant; Infant, Newborn; Infant, Small for Gestational Age; Infections; Inflammatory Bowel Diseases; Infliximab; Mercaptopurine; Neoplasms; Netherlands; Patient Admission; Pregnancy; Pregnancy Complications; Premature Birth; Prenatal Exposure Delayed Effects; Retrospective Studies; Tumor Necrosis Factor Inhibitors; Vaccines

Topics: Autoimmune Diseases; Azathioprine; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Myelodysplastic Syndromes

Topics: Autoimmune Diseases; Azathioprine; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Myelodysplastic Syndromes

Therapy-related myeloid neoplasms are a potentially life-threatening consequence of treatment for autoimmune disease (AID) and an emerging clinical phenomenon.. To query the association of cytotoxic, anti-inflammatory, and immunomodulating agents to treat patients with AID with the risk for developing myeloid neoplasm.. This retrospective case-control study and medical record review included 40 011 patients with an International Classification of Diseases, Ninth Revision, coded diagnosis of primary AID who were seen at 2 centers from January 1, 2004, to December 31, 2014; of these, 311 patients had a concomitant coded diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Eighty-six cases met strict inclusion criteria. A case-control match was performed at a 2:1 ratio.. Odds ratio (OR) assessment for AID-directed therapies.. Among the 86 patients who met inclusion criteria (49 men [57%]; 37 women [43%]; mean [SD] age, 72.3 [15.6] years), 55 (64.0%) had MDS, 21 (24.4%) had de novo AML, and 10 (11.6%) had AML and a history of MDS. Rheumatoid arthritis (23 [26.7%]), psoriasis (18 [20.9%]), and systemic lupus erythematosus (12 [14.0%]) were the most common autoimmune profiles. Median time from onset of AID to diagnosis of myeloid neoplasm was 8 (interquartile range, 4-15) years. A total of 57 of 86 cases (66.3%) received a cytotoxic or an immunomodulating agent. In the comparison group of 172 controls (98 men [57.0%]; 74 women [43.0%]; mean [SD] age, 72.7 [13.8] years), 105 (61.0%) received either agent (P = .50). Azathioprine sodium use was observed more frequently in cases (odds ratio [OR], 7.05; 95% CI, 2.35- 21.13; P < .001). Notable but insignificant case cohort use among cytotoxic agents was found for exposure to cyclophosphamide (OR, 3.58; 95% CI, 0.91-14.11) followed by mitoxantrone hydrochloride (OR, 2.73; 95% CI, 0.23-33.0). Methotrexate sodium (OR, 0.60; 95% CI, 0.29-1.22), mercaptopurine (OR, 0.62; 95% CI, 0.15-2.53), and mycophenolate mofetil hydrochloride (OR, 0.66; 95% CI, 0.21-2.03) had favorable ORs that were not statistically significant. No significant association between a specific length of time of exposure to an agent and the drug's category was observed.. In a large population with primary AID, azathioprine exposure was associated with a 7-fold risk for myeloid neoplasm. The control and case cohorts had similar systemic exposures by agent category. No association was found for anti-tumor necrosis factor agents. Finally, no timeline was found for the association of drug exposure with the incidence in development of myeloid neoplasm.

Topics: Aged; Aged, 80 and over; Arthritis, Rheumatoid; Autoimmune Diseases; Azathioprine; Case-Control Studies; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Incidence; Leukemia, Myeloid, Acute; Lupus Erythematosus, Systemic; Male; Mercaptopurine; Methotrexate; Middle Aged; Mitoxantrone; Mycophenolic Acid; Myelodysplastic Syndromes; Odds Ratio; Psoriasis; Retrospective Studies; Risk Factors; United States

Few studies exist on the frequency of thiopurine methyltransferase (TPMT) mutation in patients from Southern Europe. We aimed to evaluate the frequency of TPMT mutation in a homogeneous Sicilian cohort of patients with inflammatory bowel disease (IBD), autoimmune and hematological disorders, the rate of thiopurine-related adverse events, and its association with the TPMT genotype.. Among 105 patients with IBD, 45 with autoimmune disease, and 34 with hematologic diseases, the homozygous TPMT variant genotype was found in one patient only (0.5%), while the heterozygous TPMT genotype was identified in 8 patients (4.3%). In patients with IBD, leukopenia was observed in ten patients: one had the homozygous TPMT genotype, one the heterozygous genotype, and the remaining eight the wild type genotype.. The frequency of TPMT mutation in a Mediterranean area was low. TPMT genotyping is not a sensitive tool for predicting thiopurine-induced leukopenia.

Topics: Adult; Autoimmune Diseases; Azathioprine; Female; Hematologic Diseases; Heterozygote; Homozygote; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Italy; Leukopenia; Male; Mercaptopurine; Methyltransferases; Middle Aged; Mutation; Phenotype; Polymorphism, Genetic

Topics: Adolescent; Adrenal Cortex Hormones; Autoimmune Diseases; Cholangiopancreatography, Endoscopic Retrograde; Cholecystectomy; Cholecystitis; Chronic Pain; Humans; Immunoglobulin G; Jaundice; Liver; Male; Mercaptopurine

Although there are no standard guidelines for the treatment of autoimmune blistering diseases, azathioprine has shown good efficacy in acquired autoimmune blistering diseases, and is well tolerated. Side effects of azathioprine normally occur in mild variants. Severe reactions are due to reduced thiopurine S-methyltransferase (TPMT) or inosine triphosphate pyrophosphohydrolase (ITPA) activity. Therefore, screening for TPMT activity should be conducted in white patients and Africans, whereas Japanese should be screened for ITPA activity before therapy with azathioprine is started. Azathioprine is clinically meaningful for the treatment of pemphigus.

Topics: Animals; Autoimmune Diseases; Azathioprine; Blister; Clinical Trials as Topic; Humans; Immunosuppressive Agents; Mercaptopurine

Autoimmune pancreatitis is increasingly being diagnosed as a multiorgan disorder and a small group of patient present a diagnostic and management dilemma.. We report a complicated case of autoimmune pancreatitis with multiorgan involvement. This is the first reported case of pericardial involvement and agrees with other authors that autoimmune pancreatitis is a multisystem disorder predominantly affecting the pancreas.. In such cases more intensive immunosuppressive therapy may be necessary to get better control of the disease as is apparent from this case.

Topics: Autoimmune Diseases; Disease Progression; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Middle Aged; Pancreatitis; Pericarditis; Pericardium

We sought to assess the activity of thiopurine methyltransferase (TPMT) in 14,545 Spanish patients with different diseases amenable to treatment with azathioprine/6-mercaptopurine (6-MP), and to evaluate the proportion of patients with low TPMT activity and therefore a higher risk of myelotoxicity with these drugs. TPMT activity in red blood cells (RBCs) was measured by a radiochemical method. The association between several clinical variables and TPMT activity was assessed by multiple linear regression. We included 14,545 patients: autoimmune hepatitis (n=359 patients), inflammatory bowel disease (n=7,046), multiple sclerosis (n = 814), myasthenia gravis (n=344), pemphigus (n=133), and other diseases (n=5,849). Mean TPMT activity was 20.1 +/- 6 U/mL, but differed depending on the disease (P<.001). TPMT distribution was low (<5) in 0.5%; intermediate (5.0-13.7) in 11.9%; or high (>or=13.8) in 87.6%. Only when TPMT activity was considered separately in each disease did it reveal a normal distribution. In the multivariate analysis, gender, hematocrit, and treatment with 5-aminosalicylates/steroids/azathioprine/6-MP statistically influenced TPMT activity, although, probably, in a clinically irrelevant manner. This study shows, in a large sample of 14,545 patients, that 0.5% had low TPMT activity, indicating a higher risk of myelotoxicity with azathioprine/6-MP, a figure similar or slightly higher than that reported in other areas. Nevertheless, the trimodal distribution of TPMT activity varied depending on disease, and the proportion of patients with low activity values ranged from 0-0.8%. The drugs prescribed for the treatment of autoimmune diseases, including azathioprine/6-MP, modified TPMT activity, but the magnitude of this effect was very small and the differences found are probably irrelevant from the clinical point of view.

Topics: Adult; Autoimmune Diseases; Azathioprine; Bone Marrow Diseases; Erythrocytes; Female; Humans; Immunosuppressive Agents; Linear Models; Male; Mercaptopurine; Methyltransferases; Middle Aged; Risk Assessment; Risk Factors; Spain

Although the treatment of choice for autoimmune hepatitis is glucocorticoids, their side effects make long-term use undesirable. Therefore, other immunosuppressive agents have been used to replace glucocorticoids in the long-term treatment of autoimmune hepatitis, including azathioprine, a purine analogue. It is derived from 6-mercaptopurine, and these two drugs are often used interchangeably. However, these drugs have different toxicity profiles and may have clinically relevant differences in immunosuppressive activity in individual patients. We report 3 patients with autoimmune hepatitis who either could not tolerate or failed to improve on azathioprine but responded well to 6-mercaptopurine.

Topics: Adolescent; Adult; Autoimmune Diseases; Azathioprine; Female; Hepatitis; Humans; Male; Mercaptopurine; Remission Induction

Topics: Autoimmune Diseases; Azathioprine; Hepatitis; Humans; Mercaptopurine

MRL/Mp-lpr/lpr (MRL/l) mice spontaneously develop autoimmune kidney disease which resembles human systemic lupus erythematosus (SLE). Employing this strain of mouse, we examined the effect of several immunosuppressants and a newly synthetized anti-nephritic agent, 4-chloro-3',6'-dimethyl-2,2'-iminodibenzoic acid (TO-115) on both the development of immunological abnormalities and the clinical symptoms of autoimmune kidney disease. This study aimed to determine how much the magnitude of autoantibody suppression related to the degree of prevention of autoimmune nephritis. Immunological abnormalities were assessed by measuring the serum levels of anti-deoxyribonucleic acid and anti-trinitrophenyl antibodies, rheumatoid factor (RF), and immune complex (IC). The status of autoimmune kidney disease was monitored by means of the appearance of proteinuria and survival time and the measurement of serum levels of blood urea nitrogen (BUN) and cholesterol. Immunosuppressants such as cyclophosphamide (CY), 6-mercaptopurine (6 MP) and sodium aurothiomalate (SAT) remarkably suppressed the development of immunological abnormalities in a dose dependent manner. Interestingly, however, only CY showed the suppressive effect on the development of autoimmune kidney disease with prolongation of survival time and the excretion of proteinuria. In contrast, 6-MP and SAT did not inhibit the development of autoimmune kidney disease. On the other hand, TO-115 did not suppress the development of immunological abnormalities, but it restrained the symptoms of autoimmune kidney disease. Taken together, the suppression of autoantibody production does not always lead to prevention of the development of autoimmune kidney disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Autoantibodies; Autoimmune Diseases; Blood Urea Nitrogen; Cholesterol; Cyclophosphamide; Gold Sodium Thiomalate; Immune Complex Diseases; Kidney Diseases; Mercaptopurine; Mice; ortho-Aminobenzoates

Plasma and erythrocyte concentrations of 6-mercaptopurine (6-MP) were determined by gas chromatography-mass spectrometry. Eleven children (9 with acute lymphatic leukemia) were studied after oral intake of 6-MP doses ranging between 31 and 128 mg/m2 body surface area. The concentrations of 6-MP in plasma were found to vary considerably between patients even after dose normalization to 75 mg/m2. After dose normalization the mean peak plasma concentration was 0.68 microM (range 0.12-1.38) and the area under the plasma concentration-time curve (AUC) was 1.37 microM.h (range 0.12-3.04). The mean time taken to reach the peak concentration was 1.3 h (range 1-2), and the half-life of elimination was 1.8 h (range 0.6-2.5). No patient had detectable 6-MP concentrations 12 h after dose intake. The concentrations of 6-MP tended to be higher in erythrocytes than in plasma. The mean peak concentration in erythrocytes was 131% and the AUC 145% of that found in plasma. The mean half-life of elimination from erythrocytes was 2.0 h (range 0.7-2.8). These data indicate that 6-MP can pass through all membranes rapidly to reach intracellular concentrations equal to or even higher than in plasma. In summary, marked interindividual differences in pharmacokinetics were found, probably due to highly variable bioavailability of oral 6-MP. Further studies are needed to determine whether measurements of plasma concentrations of 6-MP can be used to optimize maintenance treatment of childhood leukemia.

Topics: Administration, Oral; Adolescent; Autoimmune Diseases; Child; Child, Preschool; Drug Evaluation; Erythrocytes; Female; Humans; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Pilot Projects; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Topics: Animals; Antibody Formation; Autoimmune Diseases; Azathioprine; Crohn Disease; Dogs; Humans; Immunity, Cellular; Immunocompetence; Immunosuppressive Agents; Kidney Transplantation; Lupus Erythematosus, Systemic; Male; Mercaptopurine; Prednisone; Rabbits

For treatment of diseases such as rheumatoid arthritis or systemic lupus erythematodes, which are initiated or sustained by immune-pathological mechanisms, various "immunosuppressive" drugs are used. There are conflicting data as to the benefit of this type of therapy. In this paper it is attempted to define a base for a more differentiated application of available drugs, since the present therapeutic approach seems rather empiric or is deducted from analogy to selected animal experiments. The investigations presented focus primarily on the behaviour of the small and medium lymphocytes of the organism, the adopted carriers of immunological (as well as autoimmune) reactivity, under conventional conditions (and under the influence of suitable drugs) as a biological supposition for the activity of "immunosuppressives". In rabbits, and mice, number and rate of proliferation of lymphoid cells is determined in untreated controls and animals treated with 6-mercaptopurine (6-MP) and cyclophosphamide (Cy), two immunosuppressive agents representing different types of pharmacological action. The elucidation why in rabbits both substances are equally immunosuppressive, whereas in mice only Cy has significant immunosuppressive activity, yields the base for a therapeutic concept of clinical immunosuppression. This species dependent activity of 6-MP can be explained by different proliferation kinetics of lymphoid cells in mouse and rabbit. Lymphocytes of the rabbit, compared to those of mice, are short-lived and have a distinctly higher proliferation rate. Thus, 6-MP, as an antiproliferative agent, leads, in the rabbit (under long-term as well as single-dose therapy) to a significant reduction of the number of small lymphocytes, whereas it reduces the long-lived lymphocytes of the mouse only marginally, thus explaining the good immunosuppressive potency in the rabbit and failure in the mouse. Cy leads, in both species, to a marked reduction of small lymphocytes and affects the long-lived cells of the mouse as well, resulting in high immunosuppressive potency in both species. In the NZB mouse, a well-fitting model of human lupus erythomatodes, Cy is successful in prophylaxis and therapy. A similar therapeutic effect cannot be obtained with 6-MP. Neither of the two groups of substances revealed selective activity on circulating T- or B-cells. According to the literature available, lymphocytes in humans are predominantly long-lived, too. Accordingly, Cy possesses a good im

Topics: Animals; Antibody Formation; Autoimmune Diseases; Cell Division; Cell Survival; Cyclophosphamide; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lymphocytes; Mercaptopurine; Mice; Mice, Inbred NZB; Rabbits; Rheumatic Diseases; Species Specificity

Topics: Adult; Antibodies; Antineoplastic Agents; Arthritis, Rheumatoid; Autoimmune Diseases; Chlorambucil; Cyclophosphamide; Humans; Hypersensitivity, Delayed; Lymphocytes; Mercaptopurine; Middle Aged; Neutrophils; Rheumatoid Factor; Thiotepa

Topics: Anemia, Aplastic; Autoimmune Diseases; Bone Marrow; Bone Marrow Cells; Female; Fluorescent Antibody Technique; Humans; Immunoglobulin G; Immunosuppressive Agents; Mercaptopurine; Middle Aged; Remission, Spontaneous

Topics: Amnion; Antigen-Antibody Reactions; Autoimmune Diseases; Culture Techniques; Cytotoxicity Tests, Immunologic; Epitopes; Female; Humans; Lymphocytes; Male; Mercaptopurine; Methods; Middle Aged; Time Factors

Topics: Adrenal Cortex Hormones; Autoimmune Diseases; Azathioprine; Chemical and Drug Induced Liver Injury; Cholestasis; Chronic Disease; Dermatomyositis; Female; Glomerulonephritis; Humans; Lupus Erythematosus, Systemic; Mercaptopurine; Polyarteritis Nodosa; Scleroderma, Systemic; Time Factors

Topics: Anemia, Hemolytic, Autoimmune; Autoimmune Diseases; Azathioprine; Humans; Lupus Erythematosus, Systemic; Mercaptopurine; Time Factors

Topics: Antigens; Autoimmune Diseases; Azathioprine; Drug Synergism; Glucocorticoids; Humans; Immune Tolerance; Immunity; Immunity, Cellular; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mercaptopurine; Methotrexate; Pemphigus; Polyarteritis Nodosa

Topics: Adolescent; Adult; Aged; Anemia, Hemolytic, Autoimmune; Antimetabolites; Arthritis, Rheumatoid; Autoimmune Diseases; Azathioprine; Female; Humans; Immunosuppressive Agents; Long-Term Care; Lupus Erythematosus, Systemic; Male; Mercaptopurine; Middle Aged; Purpura, Thrombocytopenic

Topics: Autoimmune Diseases; Azathioprine; Hepatitis; Humans; Immunosuppressive Agents; Mercaptopurine; Prednisone; Tolbutamide

Topics: Adult; Autoimmune Diseases; Azathioprine; Colitis, Ulcerative; Crohn Disease; Evaluation Studies as Topic; Humans; Immunosuppressive Agents; Male; Mercaptopurine

Topics: Animals; Antibody Formation; Antigen-Antibody Complex; Autoantibodies; Autoimmune Diseases; Bone Marrow; Coombs Test; Cyclophosphamide; Fluorescent Antibody Technique; gamma-Globulins; Hematocrit; Immunity, Cellular; Kidney; Leukocyte Count; Lupus Erythematosus, Systemic; Lymphocytes; Mercaptopurine; Mice; Monocytes

Topics: Adult; Aged; Anemia, Hemolytic, Autoimmune; Antibody Formation; Arthritis, Rheumatoid; Autoimmune Diseases; Female; Humans; Immunosuppressive Agents; Liver; Liver Function Tests; Lupus Erythematosus, Systemic; Lymphocyte Activation; Mercaptopurine; Middle Aged; Time Factors

Topics: Adolescent; Adult; Aged; Antimalarials; Autoimmune Diseases; Azathioprine; Chlorambucil; Cyclophosphamide; Follow-Up Studies; Humans; Immunosuppressive Agents; Kidney Diseases; Lupus Erythematosus, Systemic; Mercaptopurine; Middle Aged; Prednisolone; Sex Factors

Topics: Adult; Autoimmune Diseases; Azathioprine; Blood Cell Count; Busulfan; Cyclophosphamide; Female; Humans; Hypersensitivity, Delayed; Immunosuppressive Agents; Male; Melphalan; Mercaptopurine; Methotrexate; Myasthenia Gravis

Topics: Anemia, Hemolytic; Antineoplastic Agents; Autoimmune Diseases; Azathioprine; Collagen Diseases; Humans; Lupus Erythematosus, Systemic; Mercaptopurine; Sjogren's Syndrome; Thrombocytopenia

Topics: Adrenal Cortex Hormones; Anemia, Hemolytic, Autoimmune; Animals; Autoimmune Diseases; Azathioprine; Corneal Transplantation; Dactinomycin; Humans; Immunosuppressive Agents; Kidney Diseases; Mercaptopurine; Plasmacytoma; Psoriasis; Transplantation Immunology

Topics: Autoimmune Diseases; Chronic Disease; Cortisone; Cyclophosphamide; Female; Hepatitis; Hepatitis A; Humans; Liver Cirrhosis; Long-Term Care; Lupus Erythematosus, Systemic; Mercaptopurine; Penicillamine; Tuberculosis, Hepatic

Topics: Adult; Anti-Glomerular Basement Membrane Disease; Autoimmune Diseases; Biopsy; Follow-Up Studies; Glomerulonephritis; Humans; Kidney Function Tests; Kidney Glomerulus; Male; Mercaptopurine; Prednisone; Proteinuria; Sclerosis

Topics: Autoimmune Diseases; Azathioprine; Child; Cholestasis; Colitis, Ulcerative; Humans; Mercaptopurine; Methylprednisolone; Psychophysiologic Disorders

Topics: Adolescent; Adult; Aged; Anemia, Hemolytic, Autoimmune; Autoimmune Diseases; Dactinomycin; Female; Granuloma, Lethal Midline; Humans; Male; Mercaptopurine; Middle Aged; Prednisone; Purpura, Thrombocytopenic; Thrombocytopenia

Topics: Animals; Antibodies; Antibodies, Antinuclear; Autoimmune Diseases; Folic Acid Antagonists; Humans; Immune Tolerance; Mercaptopurine; Mice; Thymus Gland

Topics: Adolescent; Adult; Autoimmune Diseases; Chronic Disease; Female; Hepatitis; Humans; Liver Cirrhosis; Male; Mercaptopurine; Middle Aged; Prednisone

Topics: Adolescent; Autoimmune Diseases; Azathioprine; Child; Child, Preschool; Colitis, Ulcerative; Collagen Diseases; Cyclophosphamide; Humans; Mercaptopurine; Nephrotic Syndrome

Topics: Acute Disease; Autoimmune Diseases; Blood Protein Disorders; Blood Protein Electrophoresis; Bone Marrow; Bone Marrow Cells; Child; gamma-Globulins; Humans; Leukemia; Male; Mercaptopurine; Pyoderma

Topics: Adult; Autoimmune Diseases; Female; Hepatitis; Humans; Lupus Erythematosus, Systemic; Mercaptopurine; Neutrophils; Serologic Tests

Topics: Adult; Aged; Autoimmune Diseases; Child, Preschool; Cortisone; Dermatomyositis; Female; Humans; Lupus Erythematosus, Systemic; Mercaptopurine; Methotrexate; Middle Aged; Scleroderma, Systemic

Topics: Adolescent; Adult; Aged; Anemia, Hemolytic, Autoimmune; Autoimmune Diseases; Azathioprine; Colitis, Ulcerative; Female; Humans; Lectins; Leukemia; Male; Mercaptopurine; Middle Aged; Nephrotic Syndrome; Purpura, Thrombotic Thrombocytopenic

Topics: Animals; Autoimmune Diseases; Betamethasone; Coombs Test; Immunosuppressive Agents; Mercaptopurine; Mice

Topics: Anemia, Hemolytic, Autoimmune; Autoimmune Diseases; Azathioprine; Cyclophosphamide; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mercaptopurine; Methotrexate; Nitrogen Mustard Compounds; Purpura, Thrombocytopenic; Thioguanine

Topics: Animals; Autoimmune Diseases; Cyclophosphamide; Dactinomycin; Immunoassay; Injections, Intraperitoneal; Lymphocytes; Mercaptopurine; Plasma Cells; Prednisone; Rats; Thymidine; Transplantation Immunology; Tritium

Topics: Agammaglobulinemia; Aged; Animals; Autoimmune Diseases; Body Weight; Female; Globulins; Guinea Pigs; Humans; Immunosuppressive Agents; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Prednisone; Skin Tests; Smallpox Vaccine; Travel

Topics: Allergy and Immunology; Animals, Laboratory; Antigen-Antibody Reactions; Antineoplastic Agents; Autoimmune Diseases; Azathioprine; Colitis; Colitis, Ulcerative; Fluorescent Antibody Technique; Immunosuppressive Agents; Intestines; Mechlorethamine; Mercaptopurine; Pharmacology; Research

Topics: Animals; Antibody Formation; Autoimmune Diseases; Complement Fixation Tests; Freund's Adjuvant; Guinea Pigs; Haplorhini; Hemagglutination Tests; Hypersensitivity, Delayed; Lymphoid Tissue; Mercaptopurine; Rabbits; Thyroglobulin; Thyroiditis

Topics: Autoimmune Diseases; Diagnosis, Differential; Enzymes; Hepatitis; Humans; In Vitro Techniques; Liver Cirrhosis; Lupus Erythematosus, Systemic; Mercaptopurine; Transaminases

Topics: Allergy and Immunology; Antibody Formation; Antineoplastic Agents; Autoimmune Diseases; Cyclophosphamide; Fluorouracil; Immunity; Mannomustine; Mercaptopurine; Methotrexate; Mice; Mortality; Research; Thioguanine; Toxicology; Transplantation; Triethylenemelamine; Typhoid-Paratyphoid Vaccines; Vinblastine

Topics: Adolescent; Anemia; Anemia, Pernicious; Antineoplastic Agents; Autoimmune Diseases; Azathioprine; Clinical Enzyme Tests; Drug Therapy; gamma-Globulins; Gastritis; Glossitis; Hepatitis; Hepatitis, Chronic; Humans; Liver Function Tests; Lupus Erythematosus, Systemic; Mercaptopurine; Prednisolone; Promazine; Thyroiditis; Toxicology; Transaminases; Transplantation Immunology

Topics: Antigen-Antibody Reactions; Autoimmune Diseases; Cortisone; Hypertension; Hypertension, Renal; Infarction; Kidney; Kidney Diseases; Mercaptopurine; Pathology; Pharmacology; Precipitin Tests; Rats; Research

Topics: Adrenal Cortex Hormones; Agammaglobulinemia; Anemia; Anemia, Hemolytic; Autoimmune Diseases; Blood Protein Disorders; gamma-Globulins; Humans; Leukemia; Lymphoma; Mercaptopurine; Nitrogen Mustard Compounds; Waldenstrom Macroglobulinemia

Topics: Agammaglobulinemia; Alanine Transaminase; Animals; Antimetabolites; Autoimmune Diseases; Clinical Enzyme Tests; Encephalomyelitis; Hepatitis; Hypersensitivity; Lupus Erythematosus, Systemic; Mercaptopurine; National Institutes of Health (U.S.); Nephrosis; Nephrotic Syndrome; Prednisone; Skin Tests; United States

Topics: Antigens; Autoantibodies; Autoimmune Diseases; Autoimmunity; gamma-Globulins; Humans; Immunity; Mercaptopurine; Research