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Biomedical subjects

A Tarkowski

Publications and source records attributed to A Tarkowski.

At least 217 records · Page 12Linked to original sources
PubMed1986

Successful treatment of autoimmunity in MRL/1 mice with LS-2616, a new immunomodulator.

Autoimmune MRL/1 mice were treated with a recently developed substance with immunomodulating properties, LS-2616. Treatment was initiated at the age of 8 weeks, before the onset of clinically apparent disease, and at 16 weeks of age, after development of established lupus disease. Beneficial therapeutic effects were obtained, even when LS-2616 was administered at the lowest dose tested (1 mg/mouse/week) to 16-week-old mice. The effects of LS-2616 on longevity, as well as on development of lymphadenopathy, splenomegaly, glomerulonephritis, and vasculitis, were pronounced and were comparable with those of cyclophosphamide. The results obtained suggest a potential role for LS-2616 in the treatment of autoimmune disease in humans.

Adjuvants, Immunologic↗
PubMed1986

Generation of monoclonal rheumatoid factors after immunization with collagen II-anti-collagen II immune complexes. An anti-idiotypic antibody to anti-collagen II is also a rheumatoid factor.

Two monoclonal IgG rheumatoid factors were obtained after hybridization of spleen cells from DBA/1 mice immunized with immune complexes containing native collagen type II and a monoclonal anti-collagen II antibody. One of these rheumatoid factors reacted not only with purified murine Fc fragments, but also with Fab fragments of the anti-collagen II antibody used for immunization, whereas no reactivity was seen with Fab fragments from normal mouse IgG. The findings demonstrate the ability of immune complexes encompassing native collagen type II to induce production of IgG rheumatoid factors, and suggest that an idiotypic relationship may exist between certain rheumatoid factors and anti-collagen II antibodies.

Animals↗
PubMed1986

Impaired cutaneous delayed-type hypersensitivity in autoimmune MRL lpr/lpr mice.

A number of phenotypic and functional T-cell abnormalities have been reported in autoimmune MRL lpr/lpr (MRL/l) mice. We examined hapten-specific delayed-type hypersensitivity (DTH) responses in male and female MRL/l mice and compared them to age- and sex-matched congeneic MRL +/+ (MRL/n) mice and outbred Swiss controls. Profound defects in DTH reactivity were demonstrated in female MRL/l mice at all ages tested. In contrast MRL/l males displayed only partly impaired and selective DTH defect toward one of the two haptens used. Congeneic MRL/n females expressed lower DTH reactivity than their male littermates. We conclude that DTH responses in autoimmune MRL/l mice are defective and sex hormone related.

Age Factors↗
PubMed1986

Patterns of autoreactivity to collagen type II in autoimmune MRL/l mice.

The kinetics and mechanisms for secretion of antibodies against native and denatured collagen type II have been studied in spontaneously arthritic MRL/l mice. Circulating antibodies were quantified by an ELISA assay and frequencies of specific antibody secreting spleen cells by an ELISPOT assay. The degree of humoral immunity to collagen type II increased at late stages of the disease (6 months of age) whereas severe synovitis was seen earlier (5 months of age). Both the appearance of anti-collagen II producing cells and development of synovitis was preceded by and not correlated with a general state of polyclonal B cell activation. In MRL/l mice, collagen II specific antibodies appeared spontaneously and titres were largely unaffected by collagen II immunization. The levels of circulating anti-collagen II antibodies in MRL/l mice were lower, and the antibodies displayed lower avidities and different specificities as compared with the antibodies generated in collagen II high responder DBA/l mice after immunization with collagen II. It is suggested that the antibody response in MRL/l mice against collagen type II does not need MHC-restricted T cell help and that induction of antibody production to collagen II in MRL/l mice is triggered by joint cartilage destruction and subsequent collagen II release.

Aging↗
PubMed1986

Effects of LS-2616 administration upon the autoimmune disease of (NZB x NZW) F1 hybrid mice.

Autoimmune (NZB X NZW) F1 female hybrid mice were treated with LS-2616, a recently developed substance with immunomodulating properties. Treatment was initiated at the age of 4 months (i.e. at the early stage of the disease) as well as at 7 months of age (i.e. after the development of established lupus-like disease). Control groups treated with cyclophosphamide and physiological saline were also studied. Beneficial therapeutic effects were obtained regardless of when the treatment was initiated and the dose of LS-2616 administered (1 and 8 mg/mouse/week). The effects of LS-2616 on longevity, splenomegaly and glomerulonephritis were pronounced and sometimes comparable to those of cyclophosphamide (1.8 mg/mouse/week). The results obtained suggest that LS-2616 may be useful in the treatment of autoimmune disease in man.

Animals↗
PubMed1985

Simultaneous induction of rheumatoid factor- and antigen-specific antibody-secreting cells during the secondary immune response in man.

The production of anti-tetanus toxoid antibody and rheumatoid factor (RF) by individual peripheral blood mononuclear cells (PBMC) was studied at various times after booster immunization of healthy volunteers with tetanus toxoid (TT). TT-specific antibody-secreting cells and RF-secreting cells were assayed by the enzyme-linked immunospot (ELISPOT) assay. Cells obtained 5-9 days after immunization were found to spontaneously secrete TT-specific antibodies. This response was specific for the immunogen, was abrogated by cycloheximide and accounted for most of the immunoglobulins produced. TT-specific antibody-secreting cells were found concomitantly with cells secreting RF, mainly of the IgM isotype. Elevated levels of circulating immune complexes (CIC) containing IgG and C3 were observed shortly before the appearance of both TT-specific antibody-secreting cells and IgM RF-secreting cells. Thus, after booster immunization with TT, two major subpopulations of immunoglobulin-secreting cells appear concomitantly in the peripheral circulation: a population of cells secreting TT-specific antibody and a population of cells secreting IgM RF. It is suggested that RF production in man represents a physiological event which might be triggered by IgG-containing immune complexes formed during a secondary immune response.

Adult↗
PubMed1984

Solid-phase enzyme-linked immunospot (ELISPOT) assay for enumeration of IgG rheumatoid factor-secreting cells.

Although IgG rheumatoid factor may play an essential role in the pathogenesis of rheumatoid arthritis, there is no precise method for its specific detection at the cellular level. A modification of the recently developed enzyme-linked immunospot assay has been devised for enumeration of cells secreting IgG rheumatoid factor (IgG RF) and simultaneous quantitation of the IgG RF secreted. Specific, sensitive and simple, this new assay should provide a valuable tool for study of isotype-specific RF secretion by single cells.

Animals↗
PubMed1984

Reverse enzyme-linked immunospot assay (RELISPOT) for the detection of cells secreting immunoreactive substances.

A reverse modification of the recently described enzyme-linked immunospot assay (ELISPOT), based on localized enzyme-substrate reactions in gel, is described for the enumeration of antigen-secreting cells using petri dishes coated with specific antibodies. As a model the detection of mouse and human immunoglobulin-secreting cells has been evaluated. Simple and sensitive, this new method, termed RELISPOT, can be adapted for the quantitation of secreted antigen thus providing additional information on the metabolic state of the population of cells tested.

Adult↗
PubMed1984

Rheumatoid factors in psoriatic arthropathy and in Waaler-Rose negative rheumatoid arthritis.

Serum levels of IgG, IgA and IgM rheumatoid factor (IgG RF, IgA RF and IgM RF) were determined by means of the diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA) in 42 Waaler-Rose negative patients with psoriatic arthropathy (PsA) type 1 (arthritis with involvement of distal interphalangeal joints) and type 3 (polyarthritis of rheumatoid type) according to the criteria of Moll and Wright as well as in 53 patients with Waaler-Rose negative rheumatoid arthritis (RA). Elevated levels of RF were found in 22% of patients with PsA type 3 and 45% of patients with Waaler-Rose negative RA. In contrast, none of the patients with PsA type 1 had detectable amounts of RF. It is suggested that the presence of IgG, IgA or IgM RF in patients having psoriasis in conjunction with inflammatory polyarthritis indicates the RA nature of the joint disease and should be considered as exclusion criterion for the diagnosis of PsA.

Adolescent↗
PubMed1984

Detection of single antibody-secreting cells generated after in vitro antigen-induced stimulation of human peripheral blood lymphocytes.

Culture and assay procedures are described for the generation and the subsequent detection of single antigen-specific antibody-secreting cells after in vitro stimulation of human peripheral blood lymphocytes with tetanus toxoid. Simple, specific and sensitive, this new assay-culture system is well suited for the analysis of specific antibody production in man.

Adult↗
PubMed1984

Serum gliadin antibodies for detection and control of childhood coeliac disease.

Serum gliadin antibodies of the IgA and IgG isotypes were determined by means of the diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA) in children during different phases of coeliac disease. Fourteen children were studied before onset of dietary treatment, 16 during a period of gluten-free diet and 16 during gluten challenge. The control groups consisted of 44 children with other gastrointestinal diseases and 14 children without gastrointestinal disorders. All of the children studied had been subjected to small-intestinal biopsy. On the basis of the results obtained in this study the diagnostic sensitivity with regard to untreated coeliac disease was found to be 100% and the diagnostic specificity 97%. In 10 coeliac children followed during the phases of diagnostic evaluation antibody levels decreased in all during dietary treatment and increased in 8 during a subsequent gluten challenge. It is suggested that determination of IgA and IgG gliadin antibodies by means of DIG-ELISA may be used as a diagnostic test for coeliac disease in children and that this test may be useful in monitoring the dietary treatment in children with known coeliac disease. Moreover, the DIG-ELISA is an inexpensive and technically simple method.

Adolescent↗
PubMed1984

Detection of IgG rheumatoid factor secreting cells in autoimmune MRL/1 mice: a kinetic study.

The kinetics of appearance of cells secreting IgG rheumatoid factor (IgG RF) has been studied in MRL/l mice by means of the ELISPOT assay, a new immunoenzyme procedure. Mice of the MRL/l strain spontaneously develop an autoimmune disease associated with arthritic manifestations. IgG RF secreting splenocytes were first detected at the clinical onset of the disease at the age of 3 months. Peak frequencies of IgG RF secreting cells amounting to almost 10% of the total number of IgG secreting cells were observed at later stages. The appearance of IgG RF secreting cells was preceded by at least 1 month by elevated levels of circulating immune complexes and abnormally high numbers of IgG secreting cells. The frequencies of IgG RF secreting cells and of IgG secreting splenocytes did not follow each other at least not during the first 3 months preceding the onset of clinical disease. The data presented suggest that IgG RF production in MRL/l mice is not triggered as part of an early stage of polyclonal activation but could be induced by IgG containing immune complexes.

Aging↗
PubMed1983

A solid-phase enzyme-linked immunospot (ELISPOT) assay for enumeration of specific antibody-secreting cells.

A solid-phase enzyme-linked immunosorbent assay (ELISPOT) is described for enumeration of cells secreting specific antibody. Spleen cells from immunized mice are incubated in antigen-coated polystyrene plates. After removal of the cells, bound antibodies are demonstrated by means of an immunoenzyme procedure in which enzyme-substrate reactions are performed in agarose. Dark-brown circular zones (spots), localized in areas of the dish where antibody production has occurred, are enumerated with the naked eye. Spectrophotometric estimation of enzyme-bound activity may be performed by substituting the gel for a liquid buffer, allowing accurate estimation of the total amount of secreted antibody. Versatile, sensitive and very easy to perform, this new assay provides a useful alternative to conventional plaque-forming cell assays.

Animals↗
PubMed1983

False positive results in class-specific rheumatoid factor (RF) assays due to interaction between RF and Fc fragments of anti-immunoglobulin indicator reagents.

A recently developed, simple immunological method, diffusion-in-gel ELISA, has been adapted for class-specific determination of rheumatoid factor (RF). Evidence was obtained of an analytical error due to interaction between RF and antigenic determinants on the Fc part of the indicator immunoglobulin (Ig) molecules used. This was eliminated by replacing the usual indicator reagent, complete Ig molecules, by conjugated Fab or F(ab')2 fragments. The findings imply that unless the RF-Fc interaction mentioned is avoided in the assaying technique, false positive results may be obtained for, e.g. IgG RF and IgA RF in sera containing IgM RF.

Antibodies, Anti-Idiotypic↗
PubMed1983

Evaluation of gliadin antibodies for detection of coeliac disease.

To evaluate assay of gliadin antibodies of different immunoglobulin classes as a test for detection of coeliac disease, we analysed sera from 36 adult patients and 8 children with coeliac disease, 62 patients with other gastrointestinal diseases, and 124 blood donors with diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA). Depending on the choice of reference levels for gliadin antibodies of the IgA and IgG classes, respectively, we found a diagnostic sensitivity for coeliac disease of 93-86% and a diagnostic specificity of 95-100%. Determination of gliadin antibodies by DIG-ELISA can thus be used as a test for detection of coeliac disease and selection of patients for small-intestinal biopsy.

Adolescent↗
PubMed1983

Isotype-specific measurement of rheumatoid factor with reference to clinical features of rheumatoid arthritis.

Serum levels of IgG, IgA and IgM rheumatoid factor (IgG RF, IgA RF and IgM RF) were estimated by means of the diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA), in 90 Waaler-Rose positive and Waaler-Rose negative rheumatoid arthritis (RA) patients as well as in 60 controls. The presence of IgG and/or IgA RF was shown to be of high predictive value concerning the occurrence of systemic manifestations in RA. All RF isotypes measured were good indicators of the disease activity.

Adult↗