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Biomedical subjects

M A Persson

Publications and source records attributed to M A Persson.

At least 37 records · Page 2Linked to original sources
PubMed1991

Generation of diverse high-affinity human monoclonal antibodies by repertoire cloning.

Combinatorial libraries of antibody heavy and light chains derived from the peripheral blood lymphocytes of an individual immunized with tetanus toxoid have been expressed in Escherichia coli by using phage lambda vectors. Screening of the libraries allowed identification of a large number of human monoclonal Fab fragments specific for tetanus toxoid. Initial studies suggested considerable sequence diversity in these antibodies. The method should allow the generation of many human monoclonal antibodies of interest and the dissection of human humoral immune responses.

Amino Acid Sequence↗
PubMed1990

Increased yield of antibody-producing murine spleen cell hybridomas from fusions cultured in medium supplemented with mouse serum.

The number of monoclonal antibody-producing murine hybridomas were increased 7-10-fold in three separate fusions when supplementing the FBS-containing, or serum-free, growth factor-containing, culture medium with 5% normal mouse serum. The beneficial effect was seen in fusions of A/J and 129GIX+ spleen cells, from primary and secondary responses, and when using SP2/0 or P3X63Ag8U.1 as the fusion partner.

Animals↗
PubMed1990

Cerebrospinal fluid interleukin-6 activity in HIV infection and inflammatory and noninflammatory diseases of the nervous system.

Interleukin-6 (IL-6) activity was measured in the cerebrospinal fluid (CSF) of patients at different stages of human immunodeficiency (HIV) virus infection and of patients with multiple sclerosis (MS) or other inflammatory (OID) and noninflammatory neurological diseases (OND). In the advanced stages of HIV infection and in OID, IL-6 was detected more frequently (80 and 75% of the cases) and at higher concentrations than in the early stages of HIV infection. MS and OND (44, 48, and 44% of cases). Analysis of CSF and paired sera indicated that IL-6 production can be compartmentalized to either of the fluids. Evidence that altered blood-brain barrier functions can, at least in part, influence the CSF IL-6 levels was found in OID patients. No association was evident between intrathecal immunoglobulin synthesis and CSF IL-6 levels. Interleukin-1 (IL-1) levels were detectable in a minority of the samples from neurological patients; one OID patient had high levels of both CSF IL-1 and IL-6.

Cerebral Infarction↗
PubMed1990

The neuropeptide substance P stimulates production of interleukin 1 in human blood monocytes: activated cells are preferentially influenced by the neuropeptide.

Substance P (SP) has recently been reported to induce interleukin 1 (IL-1) production by human monocytes. This was confirmed in our experiments with human monocytes cultivated in the presence of SP or SP together with lipopolysaccharide (LPS). In addition, a wide variability of cell response to the neuropeptide was noticed. Three out of twelve cell cultures were directly stimulated by SP to release IL-1, while four additional cultures needed prestimulation with suboptimal doses of LPS, and no effect was seen in the five remaining experiments. The data may suggest that preferentially activated monocytes respond to SP. The production of IL-1 by SP-stimulated monocytes is of great interest considering the broad spectrum of activity of IL-1 and the increasing evidence of sensory neuron involvement in acute and chronic inflammatory responses.

Cells, Cultured↗
PubMed1989

Extended repertoire of specific antibodies in CSF of patients with subacute sclerosing panencephalitis compared to those with multiple sclerosis: anti-bacterial antibodies are also increased.

Serum and cerebrospinal fluid (CSF) from eight patients with subacute sclerosing panencephalitis (SSPE), 21 with multiple sclerosis (MS) and 16 controls were analyzed for IgG subclass pattern of anti-viral and anti-bacterial antibodies. In CSF of SSPE and MS patients IgG1 and IgG4 antibodies to measles and IgG1 to mumps were increased compared to the controls. In addition, the SSPE patients had elevated levels of IgG1 to PPD, teichoic acid, and to dextran in CSF. The group of MS patients had decreased levels of IgG1 antibodies to Staphylococcus aureus alpha-toxin.

Adolescent↗
PubMed1989

Stimulation of human B lymphocyte differentiation by the neuropeptides substance P and neurokinin A.

Substance P (SP) at a concentration of 10(-7) M significantly increased the number of IgG-producing cells induced by the polyclonal activator Staphylococcus aureus protein A (SpA) in 11 out of 22 cultures of enriched human blood B lymphocytes, in nine cultures SP did not significantly affect the SpA response and in three cultures IgG secretion was decreased in the presence of SP. Stimulation by SP was observed in cultures at days 6 and/or 8. In 3 out of 4 cell cultures depleted of monocytes SP did not affect the cell response to SpA stimulation. SP antagonists inhibited the enhancing effect of SP on B-cell antibody secretion induced by SpA. SP alone did not stimulate B lymphocytes. Neurokinin A (NKA) had similar effects as SP and enhanced the IgG secretion induced by SpA in 5 out of 9 experiments, in two experiments was inactive, and in one decreased the IgG secretion. The effect of SP and NKA on B lymphocytes suggest that the neuropeptides interact with the regulation of the immune response.

Amino Acid Sequence↗
PubMed1988

IgG subclass-associated affinity differences of specific antibodies in humans.

Human IgG subclasses differ in their biologic functions and are restricted as specific antibodies to certain Ag. The basis for this restriction is unknown but in order to characterize it further, we obtained serum preparations containing one single subclass by using subclass-specific mAb in affinity chromatography. Subsequently we determined the affinity of antibodies in the four IgG subclasses for gp30/p25, a hepatitis B surface Ag (HBsAg) complex, for a nine-amino acid cyclical peptide representing residues 139 to 147 of HBsAg, and for a peptide representing residues 126 to 140 of the hepatitis B virus pre-S2 region and the relative avidity of IgG1 and IgG2 antibodies for purified pneumococcal polysaccharide type 3. Affinities to the HBsAg showed a clear pattern of decreasing affinity in the order IgG1 greater than IgG2 greater than IgG3 greater than IgG4 both in sera from vaccinated and from naturally infected individuals. The relative avidities of antibodies to the polysaccharide Ag had a reverse pattern, IgG2 greater than IgG1. In individuals with or without Ig H chain gene deletions where the anti-HBsAg response was restricted to one subclass, the affinity was similar to that observed for the same subclass in sera from individuals who in addition possessed high or low affinity antibodies of other subclasses.

Adult↗
PubMed1988

Neutralization capacity and antibody dependent cell-mediated cytotoxicity of separated IgG subclasses 1, 3 and 4 against herpes simplex virus.

IgG subclasses 1, 3 and 4 in sera from herpes simplex virus type 1 (HSV-1) seropositive donors were separated and their functions assayed. The main neutralizing activity to HSV-1 was found in the IgG1 fractions. Both IgG3 and IgG4 possessed higher neutralizing titres than IgG1 in relation to the respective HSV IgG subclass enzyme-linked immunosorbent assay (ELISA) titre. Addition of complement resulted in a strong enhancement of IgG3 neutralizing activity. HSV neutralizations by IgG1 and, surprisingly, IgG4 were also somewhat enhanced by complement. With the addition of complement, the contribution to neutralizing activity of IgG3 was calculated to increase from 31 to 40% of total IgG in HSV neutralization in native sera. The avidities of the IgG fractions to HSV glycoprotein C (gC) were estimated in a few sera but could not be correlated to neutralization results. Antibody dependent cell-mediated cytotoxicity (ADCC) was detectable mainly in IgG1 and 3 fractions of sera with high anti-HSV antibody titres.

Antibody Affinity↗
PubMed1987

The use of human antigen-specific monoclonal antibodies in an enzyme-linked immunosorbent assay for the determination of anti-HBsAg antibody subclasses.

A human monoclonal anti-HBsAg antibody (IgG1, lambda) was used as a reference for an ELISA determination of the serum levels of anti-HBsAg antibodies in human volunteers after vaccination with H-B vax. The IgG subclass distribution of specific antibodies showed a marked dominance of IgG1 antibodies. In addition, small amounts of specific IgG4 antibodies were occasionally found, suggesting a different pattern from that found after natural disease. The novel use of a human monoclonal antibody to measure specific antibodies may give a more accurate determination of specific IgG subclass levels than previously available methods.

Antibodies, Monoclonal↗
PubMed1987

Preparation of human sera containing one single IgG subclass using affinity chromatography.

Monoclonal antibodies reactive against one or three human IgG subclasses were immobilised on agarose beads, put into columns and used in combination with coupled polyclonal anti-IgA and anti-IgM reactive gels to obtain serum preparations devoid of IgA, IgM and all but one IgG subclass. This was possible after one single run over the appropriate combination of columns; only for IgG4 preparations was a second purification step sometimes required to reach purity. Negative affinity chromatography was used throughout, thus the resulting preparations had not been exposed to high ionic strength conditions, non-physiological pH buffers or chaotropic agents in concentrations ordinarily used to elute bound material from affinity columns. The yield was approximately 50% and 20-30% if two runs were required. Regeneration of the columns permitted repetitive use, so far up to 30 times without substantial loss of activity. The protocol offers an easy, comparatively fast and reproducible method to obtain human serum preparations containing only IgG1,2,3, or 4.

Antibodies, Monoclonal↗
PubMed1986

Immunoglobulin G (IgG) and IgA subclass pattern of human antibodies to Shigella flexneri and Salmonella serogroup B and D lipopolysaccharide O antigens.

The subclass distribution of human serum antibodies to the O-antigenic lipopolysaccharides of Salmonella serogroups B and D and to Shigella flexneri serotypes 1b, 2a, and 4a lipopolysaccharide antigens were analyzed in an enzyme-linked immunosorbent assay with monoclonal antibodies to the immunoglobulin subclasses. The patients had culture-verified Salmonella (17 Swedes) or Shigella flexneri (23 Vietnamese; 11 children and 12 adults) infections. Consecutive samples drawn during 1 year postinfection were investigated. Antibodies to the Salmonella antigens were mainly of the immunoglobulin G1 (IgG1), IgA1, and IgA2 subclasses. For the Salmonella serogroup B O polysaccharide, the IgA1 and IgA2 subclasses had peak values earlier than (6/9) or coinciding with the IgG1 (3/9) peak value. Furthermore, the IgA2 response to Salmonella serogroup B was positively correlated to the duration of the carrier state (P less than 0.001); the corresponding IgA1 response was less well correlated but was still significant (P less than 0.02). In the case of the Shigella flexneri O polysaccharide, specific antibodies appeared mainly in the IgG1 and IgA1 subclasses. Some IgG2 was also found, surprisingly even in very young patients. No subclass shift with time within the immunoglobulin classes was noted in any of the groups.

Antibodies, Bacterial↗
PubMed1986

Serum and cerebrospinal fluid antibodies against myelin basic protein and their IgG subclass distribution in multiple sclerosis.

IgG class antibodies reactive with myelin basic protein (MBP) were determined by enzyme-linked immunosorbent assay (ELISA) in serum and cerebrospinal fluid (CSF) of 37 patients with multiple sclerosis and a control group of 32 patients with tension headache or psychoneurosis. Using standardised amounts of IgG from CSF and serum in ELISA, significantly higher mean antibody levels were found in CSF as well as in serum from the patients with multiple sclerosis. Ten (27%) of the multiple sclerosis CSF samples and 15 (41%) of the multiple sclerosis sera revealed anti MBP antibody levels exceeding 2 SD of the control group. Seven patients (19%) showed exclusive or higher levels of anti MBP antibodies in CSF, suggesting synthesis within the central nervous system. Analysis by ELISA for IgG subclasses of anti MBP antibodies revealed that they were restricted to IgG 1 in four patients and IgG 3 in one.

Enzyme-Linked Immunosorbent Assay↗
PubMed1985

Enzyme-linked immunosorbent assay for subclass distribution of human IgG and IgA antigen-specific antibodies.

In this study we describe an ELISA using monoclonal antibodies to IgG 1, 2, 3, 4, IgA1 and IgA2 for determining the subclass distribution of human-specific antibodies. No cross-reactivity of the subclass-specific reagents under the conditions used was observed. The sensitivity was 0.5 ng/ml for IgG1, 3, 4; 1.5 ng/ml for IgG2 and 50 ng/ml for IgA1 and IgA2. The reproducibility as described by the coefficient of variation calculated on repeated runs was 8-26% if the data were obtained by relating the absorbance values to a positive serum run in the assay, 17-58% when relating the OD figures to those of a standard myeloma plate. The method may be considered semiquantitative with high sensitivity and specificity, easy to handle and with small day-to-day variation. The assay has been applied to a number of antigens of protein and polysaccharide nature.

Antibodies, Monoclonal↗
PubMed1985

Ontogeny of IgG2 antibodies against S. aureus teichoic acid in normal and immunodeficient children.

Anti-teichoic acid antibodies of various subclasses were found to be effectively transported across the placenta during pregnancy. In adults these antibodies are mainly of the IgG2 subclass although substantial amounts of specific IgG1 antibodies may also be found. During ontogeny, specific IgG1 antibodies develop during the second year of life whereas specific IgG2 antibodies appear markedly later. In IgG2 deficient children, prolonged deficiency of specific anti-teichoic acid antibodies was observed, suggesting a lack of maturation of the appropriate idiotype(s). In children who received a bone marrow transplant from adult donors, engraftment of IgG2 producing cells could be seen, thus transferring the ability to produce specific antibodies.

Adolescent↗
PubMed1985

Immunoglobulin subclass distribution of human anti-carbohydrate antibodies: aberrant pattern in IgA-deficient donors.

The IgG and IgA subclass distribution of anti-carbohydrate antibodies in normal and immunodeficient donors was investigated. In normal donors, the specific anti-dextran antibodies were mainly of the IgG2 and IgA2 subclass, although substantial amounts of antibodies could also be of the IgG1 subclass. In children, IgG1 was the predominant subclass expressed. An aberrant IgG subclass distribution pattern of specific antibodies occurred in some IgA-deficient donors, with preferential expression of IgG1 and IgG3 anti-dextran antibodies.

Adult↗